Night shift work and risk of breast cancer in women: the Generations Study cohort.
It is plausible that night shift work could affect breast cancer risk, possibly by melatonin suppression or circadian clock disruption, but epidemiological evidence is inconclusive. Using serial questionnaires from the Generations Study cohort, we estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer in relation to being a night shift worker within the last 10 years, adjusted for potential confounders. Among 102,869 women recruited in 2003-2014, median follow-up 9.5 years, 2059 developed invasive breast cancer. The HR in relation to night shift work was 1.00 (95%CI: 0.86-1.15). There was a significant trend with average hours of night work per week (P = 0.035), but no significantly raised risks for hours worked per night, nights worked per week, average hours worked per week, cumulative years of employment, cumulative hours, time since cessation, type of occupation, age starting night shift work, or age starting in relation to first pregnancy. The lack of overall association, and no association with all but one measure of dose, duration, and intensity in our data, does not support an increased risk of breast cancer from night shift work in women.


Quasi-stationary wave patterns inside infinite-strip open resonators.
The quasi-stationary wave patterns inside a two-mirror optical resonator are evaluated as the sum of a progressive and a regressive wave by assuming the mirrors to be illuminated by the fundamental mode of the resonator at a resonance frequency. The progressive and the regressive waves are also evaluated in the case of the first-order mode. Calculations are made for an infinite-strip Fabry-Perot resonator, as well as for a cylindrical and a confocal resonator, with Fresnel number N = 1.


Quantifying the uncertainty in heritability.
The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach, in which heritability is estimated using maximum likelihood and its variance is quantified through an asymptotic normal approximation. An alternative approach is to quantify the uncertainty in heritability through its Bayesian posterior distribution. In this paper, we develop the latter approach, make it computationally efficient and compare it to the frequentist approach. We show theoretically that, for a sufficiently large sample size and intermediate values of heritability, the two approaches provide similar results. Using the Atherosclerosis Risk in Communities cohort, we show empirically that the two approaches can give different results and that the variance/uncertainty can remain large.


Analysis of volatile profiles of fermenting grape must by headspace solid-phase dynamic extraction coupled with gas chromatography-mass spectrometry (HS-SPDE GC-MS): novel application to investigate problem fermentations.
The occurrence of stuck and sluggish wine fermentations is a persisting problem in the wine industry worldwide. This study illustrates the suitability of headspace solid-phase dynamic extraction coupled with gas chromatography-mass spectrometry (HS-SPDE GC-MS) for wine analysis and the subsequent application to discriminate between control and problem fermentations using partial least-squares discriminant analysis (PLS-DA) models. The specific analytical technique is relatively new and has not yet to the authors' knowledge been evaluated for the analysis of wine within this context of problem fermentations. HS-SPDE GC-MS was used to determine 68 volatile compounds (higher alcohols, fatty acids, esters, and carbonyl compounds) in 94 monovarietal fermenting must samples consisting of 56 red and 38 white cultivars. PLS-DA models showed the potential to discriminate between control and problem fermentations using corrected peak area headspace data for the 68 analytes. This possibility to discriminate between problem and control fermentations with only the headspace data could possibly be applied for the prediction of problem fermentations in future studies and to better understand the chemical causes of problem fermentations.


IFNγ signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells.
IFNγ is an immune mediator with concomitant pro- and anti-tumor functions. Here, we provide evidence that IFNγ directly acts on intra-tumoral CD8 T cells to restrict anti-tumor responses. We report that expression of the IFNγ receptor β chain (IFNγR2) in CD8 T cells negatively correlates with clinical responsiveness to checkpoint blockade in metastatic melanoma patients, suggesting that the loss of sensitivity to IFNγ contributes to successful antitumor immunity. Indeed, specific deletion of IFNγR in CD8 T cells promotes tumor control in a mouse model of melanoma. Chronic IFNγ inhibits the maintenance, clonal diversity and proliferation of stem-like T cells. This leads to decreased generation of T cells with intermediate expression of exhaustion markers, previously associated with beneficial anti-tumor responses. This study provides evidence of a negative feedback loop whereby IFNγ depletes stem-like T cells to restrict anti-tumor immunity. Targeting this pathway might represent an alternative strategy to enhance T cell-based therapies.


Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter.
Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.


Desensitization and resensitization of rat pituitary tumor cells in long-term culture to the effects of the somatostatin analogue SMS 201-995 on cell growth and prolactin secretion.
Cultured cells, prepared from the transplantable rat prolactin (rPRL)-secreting rat pituitary tumor 7315b were found to be inhibited in a dose-dependent way in their cell growth and hormone secretion by the somatostatin analogue SMS 201-995 (Sandostatin). In short-term (1 week) experiments these effects were not time dependent and of similar magnitude (an inhibition of approximately 50% at 100 nM SMA 201-995) both for the rate of rPRL secretion and for the rate of incorporation of tritiated thymidine into the tumor cells. When freshly isolated 7315b cells were used for long-term experiments (38 days), continuous exposure to SMS 201-995 at all concentrations tested (0.1 nM, 10 nM, and 1 microM) resulted in desensitization of the cells to the peptide with respect to rPRL secretion. Using a stable cell line derived from the long-term experiment and designated 7315c, we show that (a) long-term exposure of 7315c cells to SMS 201-995 leads to loss of sensitivity with respect to both rPRL secretion and cell growth, (b) this loss of sensitivity is accompanied by complete disappearance of the somatostatin receptors from the cells, (c) withdrawal of treatment from desensitized cells leads to reappearance of receptors and of sensitivity to SMS 201-995, showing that selection for a non-receptor-bearing population was not the cause of desensitization, and (d) since these experiments were carried out with a pure population of 7315c cells the effects of SMS 201-995 are direct effects on these cells and not effects mediated by other cell or organ systems.


Genome-wide association study of cerebral small vessel disease reveals established and novel loci.
Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 × 10-8] at 1q22; rs72932727 (P = 1.7 × 10-8) at 2q33; and rs9515201 (P = 5.3 × 10-10) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 × 10-4 in tibial nerve), NBEAL1, FAM117B and CARF (P < 2.1 × 10-7 in arteries) and COL4A2 and COL4A1 (P < 0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P < 8.5 × 10-7) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS.


First Report of Cytospora Canker Caused by Cytospora chrysosperma on White Poplar in Israel.
A new disease, causing death of mature white poplar trees (Populus alba L.), was observed in Hulla Valley in northern Israel in the summer of 2002. The affected branches turned yellowish brown, and the inner bark turned black. The bark dried out and separated from the underlying wood. Later, copious, dark pycnidia developed on the dead bark. The pycnidia had a diameter of 650 µm (n = 50), ranging 600 to 800 µm. Under moist conditions, spore masses oozed out in long, reddish brown, coiled tendrils. The spores were hyaline, one-celled, and slightly curved, 1.1 × 5.5 µm (5.0 to 6.0 µm) (n = 100), and somewhat smaller than those reported by Schreiner (1). A herbarium specimen was deposited at the U.S. National Fungus Collections (BPI 843390). Isolations made from affected branches yielded colonies of Cytospora chrysosperma (Pers.:Fr.)Fr. with a whitish orange mycelium that turned dark green 11 days later. Its growth rate on potato dextrose agar at 25°C was 7.1 mm per day. Exposure to daylight induced pycnidial development after 3 to 4 weeks. Inoculation of eight 1-year-old seedlings of white poplar and willow (Salix acmophylla Boiss) proved the pathogenicity of several isolates of C. chrysosperma. The average canker length at 28 days after inoculation was 28.0 and 14.5 cm on white poplar and willow, respectively, indicating the higher susceptibility of P. alba. No cankers developed on the control seedlings. Reisolations from inoculated plants yielded C. chrysosperma. To our knowledge, this is the first report of Cytospora canker on white poplar in Israel. Reference: (1) E. J. Schreiner. Am. J. Bot.18:1, 1931.


Scanning tunneling microscopy, spectroscopy, and nanolithography of epitaxial graphene chemically modified with aryl moieties.
The reduction of diazonium salts has recently been proposed as a robust covalent modification scheme for graphene surfaces. While preliminary studies have provided indirect evidence that this strategy decorates graphene with aryl moieties, the molecular ordering and conformation of the resulting adlayer have not been directly measured. In this Article, we report molecular-resolution characterization of the adlayer formed via the spontaneous reduction of 4-nitrophenyl diazonium (4-NPD) tetrafluoroborate on epitaxial graphene on SiC(0001) using ultrahigh vacuum (UHV) scanning tunneling microscopy (STM) and spectroscopy (STS). An atomically flat inhomogeneous layer of covalently bonded organic molecules is observed after annealing the chemically treated surface at ∼500 °C in UHV. STM and STS results indicate that the adlayer consists predominantly of aryl oligomers that sterically prevent uniform and complete covalent modification of the graphene surface. The adsorbed species can be selectively desorbed by the STM tip above a threshold sample bias of -5 V and tunneling current of 1 nA, thus enabling the fabrication of a diverse range of graphene nanopatterns at the sub-5 nm length scale.


Predictability of the terrestrial carbon cycle.
Terrestrial ecosystems sequester roughly 30% of anthropogenic carbon emission. However this estimate has not been directly deduced from studies of terrestrial ecosystems themselves, but inferred from atmospheric and oceanic data. This raises a question: to what extent is the terrestrial carbon cycle intrinsically predictable? In this paper, we investigated fundamental properties of the terrestrial carbon cycle, examined its intrinsic predictability, and proposed a suite of future research directions to improve empirical understanding and model predictive ability. Specifically, we isolated endogenous internal processes of the terrestrial carbon cycle from exogenous forcing variables. The internal processes share five fundamental properties (i.e., compartmentalization, carbon input through photosynthesis, partitioning among pools, donor pool-dominant transfers, and the first-order decay) among all types of ecosystems on the Earth. The five properties together result in an emergent constraint on predictability of various carbon cycle components in response to five classes of exogenous forcing. Future observational and experimental research should be focused on those less predictive components while modeling research needs to improve model predictive ability for those highly predictive components. We argue that an understanding of predictability should provide guidance on future observational, experimental and modeling research.


Correlates of objectively measured physical activity and sedentary behaviour in English children.
Evidence on the correlates of objectively measured physical activity and sedentary behaviour in childhood is limited. This study aimed to identify correlates of physical activity and sedentary behaviour among 7-year-old children in England. Physical activity was measured using Actigraph accelerometry in 480 participants as part of the Gateshead Millennium Study during 2006-07. Twenty-two potential correlates across five domains (demographic and biological; psychological, cognitive and emotional; behavioural; social and cultural; physical environmental) were tested for associations with total volume of habitual physical activity, moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour. Multiple linear regression analysis was used. Seven correlates, including four that are potentially modifiable, were significantly associated with total physical activity, MVPA and sedentary behaviour in final models: gender, child weight status, maternal age, child interest in active play, active commuting to school, parenting practice and season. Four of these variables were significantly associated with all three constructs in final models. The final models explained 18, 18 and 24% of variance in total volume of physical activity, MVPA and sedentary behaviour, respectively. A number of potentially modifiable factors are associated with increased physical activity and/or reduced sedentary behaviour in English children. These could be valuable targets of future interventions.


Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study.
On the basis of clinical and pathologic criteria, endometrial carcinoma has been distinguished as types I (mainly endometrioid) and II (nonendometrioid). Limited data suggest that these subtypes have different risk factor profiles. The authors prospectively evaluated risk factors for types I (n = 1,312) and II (n = 138) incident endometrial carcinoma among 114,409 women in the National Institutes of Health (NIH)-AARP Diet and Health Study (1995-2006). For individual risk factors, relative risks were estimated with Cox regression by subtype, and P(heterogeneity) was assessed in case-case comparisons with type I as the referent. Stronger relations for type I versus Type II tumors were seen for menopausal hormone therapy use (relative risk (RR) of 1.18 vs. 0.84; P(heterogeneity) = 0.01) and body mass index of ≥30 vs. <30 kg/m2 (RR of 2.93 vs. 1.83; P(heterogeneity) = 0.001). Stronger relations for type II versus type I tumors were observed for being black versus white (RR of 2.18 vs. 0.66; P(heterogeneity) = 0.0004) and having a family history of breast cancer (RR of 1.93 vs. 0.80; P(heterogeneity) = 0.002). Other risk factor associations were similar by subtype. In conclusion, the authors noted different risk factor associations for Types I and II endometrial carcinomas, supporting the etiologic heterogeneity of these tumors. Because of the limited number of Type II cancers, additional evaluation of risk factors will benefit from consortial efforts.


NADPH Oxidase-Mediated ROS Production Determines Insulin's Action on the Retinal Microvasculature.
To determine whether insulin induces nitric oxide (NO) formation in retinal microvessels and to examine the effects of high glucose on the formation of NO. Freshly isolated rat retinal microvessels were incubated in normal (5.5 mM) or high (20 mM) glucose with or without insulin (100 nM). The levels of insulin-induced NO and reactive oxygen species (ROS) in the retinal microvessels were determined semiquantitatively using fluorescent probes, 4,5-diaminofluorescein diacetate, and hydroethidine, respectively, and a laser scanning confocal microscope. The insulin-induced changes of NO in rat retinal endothelial cells and pericytes cultured at different glucose concentrations (5.5 and 25 mM) were determined using flow cytometry. Nitric oxide synthase (NOS) protein levels were determined by Western blot analysis; intracellular levels of ROS were determined using fluorescence-activated cell sorting (FACS) analysis of ethidium fluorescence; and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase RNA expression was quantified using real-time PCR. Exposure of microvessels to insulin under normal glucose conditions led to a significant increase in NO levels; however, this increase was significantly suppressed when the microvessels were incubated under high glucose conditions. Intracellular levels of ROS were significantly increased in both retinal microvessels and cultured microvascular cells under high glucose conditions. The expression of NOS and NADPH oxidase were significantly increased in endothelial cells and pericytes under high glucose conditions. The increased formation of NO by insulin and its suppression by high glucose conditions suggests that ROS production mediated by NADPH oxidase is important by insulin's effect on the retinal microvasculature.


Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study.
The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk. We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated. We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9.1, manic psychosis 8.0) and Black Africans (schizophrenia 5.8, manic psychosis 6.2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study. Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.


A "Double-Edged" Scaffold: Antitumor Power within the Antibacterial Quinolone.
In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today's predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents.


Lay health workers in primary and community health care for maternal and child health and the management of infectious diseases.
Lay health workers (LHWs) are widely used to provide care for a broad range of health issues. Little is known, however, about the effectiveness of LHW interventions. To assess the effects of LHW interventions in primary and community health care on maternal and child health and the management of infectious diseases. For the current version of this review we searched The Cochrane Central Register of Controlled Trials (including citations uploaded from the EPOC and the CCRG registers) (The Cochrane Library 2009, Issue 1 Online) (searched 18 February 2009); MEDLINE, Ovid (1950 to February Week 1 2009) (searched 17 February 2009); MEDLINE In-Process & Other Non-Indexed Citations, Ovid (February 13 2009) (searched 17 February 2009); EMBASE, Ovid (1980 to 2009 Week 05) (searched 18 February 2009); AMED, Ovid (1985 to February 2009) (searched 19 February 2009); British Nursing Index and Archive, Ovid (1985 to February 2009) (searched 17 February 2009); CINAHL, Ebsco 1981 to present (searched 07 February 2010); POPLINE (searched 25 February 2009); WHOLIS (searched 16 April 2009); Science Citation Index and Social Sciences Citation Index (ISI Web of Science) (1975 to present) (searched 10 August 2006 and 10 February 2010). We also searched the reference lists of all included papers and relevant reviews, and contacted study authors and researchers in the field for additional papers. Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to improve maternal or child health or the management of infectious diseases. A 'lay health worker' was defined as any health worker carrying out functions related to healthcare delivery, trained in some way in the context of the intervention, and having no formal professional or paraprofessional certificate or tertiary education degree. There were no restrictions on care recipients. Two review authors independently extracted data using a standard form and assessed risk of bias. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the study results were combined and an overall estimate of effect obtained. Eighty-two studies met the inclusion criteria. These showed considerable diversity in the targeted health issue and the aims, content, and outcomes of interventions. The majority were conducted in high income countries (n = 55) but many of these focused on low income and minority populations. The diversity of included studies limited meta-analysis to outcomes for four study groups. These analyses found evidence of moderate quality of the effectiveness of LHWs in promoting immunisation childhood uptake (RR 1.22, 95% CI 1.10 to 1.37; P = 0.0004); promoting initiation of breastfeeding (RR = 1.36, 95% CI 1.14 to 1.61; P < 0.00001), any breastfeeding (RR 1.24, 95% CI 1.10 to 1.39; P = 0.0004), and exclusive breastfeeding (RR 2.78, 95% CI 1.74 to 4.44; P <0.0001); and improving pulmonary TB cure rates (RR 1.22 (95% CI 1.13 to 1.31) P <0.0001), when compared to usual care. There was moderate quality evidence that LHW support had little or no effect on TB preventive treatment completion (RR 1.00, 95% CI 0.92 to 1.09; P = 0.99). There was also low quality evidence that LHWs may reduce child morbidity (RR 0.86, 95% CI 0.75 to 0.99; P = 0.03) and child (RR 0.75, 95% CI 0.55 to 1.03; P = 0.07) and neonatal (RR 0.76, 95% CI 0.57 to 1.02; P = 0.07) mortality, and increase the likelihood of seeking care for childhood illness (RR 1.33, 95% CI 0.86 to 2.05; P = 0.20). For other health issues, the evidence is insufficient to draw conclusions regarding effectiveness, or to enable the identification of specific LHW training or intervention strategies likely to be most effective. LHWs provide promising benefits in promoting immunisation uptake and breastfeeding, improving TB treatment outcomes, and reducing child morbidity and mortality when compared to usual care. For other health issues, evidence is insufficient to draw conclusions about the effects of LHWs.


Illness in children after international travel: analysis from the GeoSentinel Surveillance Network.
By using a large, multicenter database, we investigated the characteristics and morbidities of 1591 children returning from 218 global destinations and presenting for care in 19 countries. Data reported to the GeoSentinel Surveillance Network between January 1997 and November 2007 were analyzed, to assess demographic features, travel characteristics, and clinical diagnoses of ill pediatric travelers. Data were compared between children and adults and among 3 pediatric age groups (0-5 years, 6-11 years, and 12-17 years). Children were predominantly tourist travelers returning from Asia, sub-Saharan Africa, or Latin America. Compared with adults, children disproportionately presented within 7 days after return, required hospitalization, lacked pretravel health advice, and had traveled for the purpose of visiting friends and relatives. Diarrhea (28%), dermatologic conditions (25%), systemic febrile illnesses (23%), and respiratory disorders (11%) accounted for the majority of diagnoses reported for children. No fatalities were reported. Diarrhea occurred disproportionately among children after exposure to the Middle East/North Africa, dermatologic conditions after exposure to Latin America, systemic febrile illnesses after exposure to sub-Saharan Africa or Asia, and respiratory disorders after exposure to Europe or North America. The proportionate morbidity rates of travel-associated diseases differed among the pediatric age groups and between children and adults. The health care utilization patterns before and after travel and the profiles of travel-associated health problems differed between children and adults. Health professionals providing pretravel advice need to consider destination- and age-specific susceptibility to travel-related morbidities and develop prevention strategies accordingly.


Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years.
Children born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW, <1500 g; hereafter called VP/VLBW) are at risk for behavioural and emotional problems during school age and adolescence. At school entrance these problems may hamper academic functioning, but evidence on their occurrence at this age in VP/VLBW children is lacking. To provide information on academic functioning of VP/VLBW children and to examine the association of behavioural and emotional problems with other developmental problems assessed by paediatricians. A cohort of 431 VP/VLBW children aged 5 years (response rate 76.1%) was compared with two large national samples of children of the same age (n = 6007, response rate 86.9%). Behavioural and emotional problems measured by the Child Behavior Checklist (CBCL), and paediatrician assessment of other developmental domains among VP/VLBW children. The prevalence rate of a CBCL total problems score in the clinical range was higher among VP/VLBW children than among children of the same age from the general population (13.2% v 8.7%, odds ratio 1.60 (95% confidence interval 1.18 to 2.17)). Mean differences were largest for social and attention problems. Moreover, they were larger in children with paediatrician-diagnosed developmental problems at 5 years, and somewhat larger in children with severe perinatal problems. At school entrance, VP/VLBW children are more likely to have behavioural and emotional problems that are detrimental for academic functioning. Targeted and timely help is needed to support them and their parents in overcoming these problems and in enabling them to be socially successful.


Constitutive expression of Escherichia coli tat genes indicates an important role for the twin-arginine translocase during aerobic and anaerobic growth.
The transcription start sites for the tatABCD and tatE loci, encoding components of the Tat (twin-arginine translocase) protein export pathway, have been identified. Expression studies indicate that the tatABCD and tatE transcription units are expressed constitutively. Translational fusion experiments suggest that TatA is synthesized at a much higher level than the other Tat proteins.


Pulmonary alveolar epithelial inducible NO synthase gene expression: regulation by inflammatory mediators.
Nitric oxide (.NO) is a short-lived mediator that can be induced by different cytokines and lipopolysaccharide (LPS) in a variety of cell types and produces many physiological and metabolic changes in target cells. In the current study, we show that a combination of cytokines, LPS, and zymosan-activated serum (ZAS; called for convenience cytomix Z) induces production of high concentrations of the NO oxidation products nitrite (NO2-) and nitrate (NO3-) by cultured rat fetal lung epithelial type II cells in a time-dependent fashion. Interferon-gamma and tumor necrosis factor-alpha alone did not significantly affect .NO synthesis, whereas ZAS, LPS, and interleukin-1 beta caused only a modest increase in formation of .NO oxidation products. Production of NO2- and NO3- was inhibited by NG-monomethyl-L-arginine and cyclohexmide. After exposure of these cells to a combination of the above cytokines, Escherichia coli LPS, and ZAS (cytomix Z), enhanced inducible nitric oxide synthase (iNOS) expression was indicated by an elevation in steady-state mRNA specific for iNOS (via Northern blot analysis) and increased immunofluorescence for iNOS after cell permeabilization, incubation with anti-iNOS antibody, and treatment with Cy3.18-conjugated rabbit-specific antibody. The extent of inflammatory mediator-induced.NO production by alveolar epithelium, which exceeds that of other lung cell types, reveals new insight into mechanisms of pulmonary host defense and pathways of free radical-mediated lung injury.


Maturation of auditory brainstem projections and calyces in the congenitally deaf (dn/dn) mouse.
The deaf dn/dn mouse is a valuable model of human congenital deafness. In this study we used the lipophylic dye DiA to trace auditory nerve and cochlear nucleus projections in the dn/dn mouse. In both normal and deaf mice, the ipsilateral projections from the anteroventral cochlear nucleus (AVCN) to the lateral superior olive (LSO), and the contralateral projections from the AVCN to the medial nucleus of the trapezoid body (MNTB) were intact. With age, there was a noted increase in the fenestration of the endbulb and calyx of Held, and this morphological maturation was also observed in the deaf mice, although there was a significant difference in total endbulb volume at P20 between normal and deaf mice. However, total calyceal volume was not significantly different between normal and deaf mice. There was electrophysiological evidence of in vivo spontaneous ventral cochlear nucleus activity in normal and deaf animals, indicating that this activity may be responsible for the appropriate connectivity in the deaf mice. Our results indicate that congenital deafness caused by the dn/dn mutation does not result in aberrant projections between the AVCN and the ipsilateral MNTB and contralateral LSO but can cause abnormalities in endbulb size.


Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa.
Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.


Mapping of human X-linked hypophosphataemic rickets by multilocus linkage analysis.
Eleven families with X-linked dominant hypophosphataemic rickets (HPDR) have been typed for a series of X chromosome markers. Linkage with probe 99.6 (DXS41) was demonstrated with a peak lod score of 4.82 at 10% recombination. Multilocus linkage analysis showed that HPDR maps distal to 99.6; this probe has previously been located at Xp22.31-p21.3 by in situ hybridisation. In the mouse hypophosphataemia (Hyp) maps to the distal part of the X chromosome; our location in man is consistent with a scheme which relates the mouse and human X chromosomes by two rearrangements. No marker has yet been found which shows no recombination with HPDR.


Effects of acupuncture on smoking cessation or reduction for motivated smokers.
This study was undertaken to examine the effects of acupuncture on smoking reduction and possibly also cessation and to examine whether some acupoints are more effective than others for smoking cessation. A total of 46 healthy men and women, 39 +/- 9 years of age (mean +/- SD), who smoked 20 +/- 6 cigarettes per day and had smoked for 23 +/- 8 years, and who wanted to quit smoking, volunteered to participate. The subjects were randomly assigned to two groups. One group was given acupuncture treatment at points previously used for anti-smoking (test group, TG). The other group was given acupuncture treatment at points assumed to have no effect for smoking cessation (control group, CG). Before each treatment and after the last treatment each subject answered questionnaires about his or her smoking habits and attitudes. In addition the concentrations of serum cotinine, serum thiocyanate, serum peroxides, and plasma fibrinogen were measured before the first and after the last acupuncture treatment. The daily cigarette consumption fell during the treatment period in both groups, but the reduction was larger for TG than for CG (P < 0.002). Altogether 31% of subjects in TG had quit smoking completely at the end of the treatment, compared with none in CG. For TG the concentrations of cotinine and thiocyanate were reduced significantly after the treatment period (P < 0.001), but no significant reductions were observed for CG. For both groups the taste of tobacco worsened during the treatment period, but the effect was more pronounced for TG than for CG (P < 0.05). The desire to smoke fell significantly in both groups after treatment, and the reduction was larger for TG than for CG (P < 0.001). No significant changes in serum peroxides and plasma fibrinogen concentrations were observed during the treatment period for either group. This study suggests that acupuncture may help motivated smokers to reduce their smoking or even quit smoking completely. Different acupoints appear to have different effects for smoking cessation and reduction.


Influence of a Multitask Paradigm on Motor and Cognitive Performance of Military and Law Enforcement Personnel: A Systematic Review.
To review the current literature investigating if performance of tactical athletes under multitask paradigms is different than performance under single-task paradigms. The authors completed a search of the literature published from January 01, 2000, to June 01, 2018, using key search terms in PubMed, Web of Science, SPORTDiscus, and Defense Technical Information Center (DTIC) databases. Studies that met inclusion and exclusion criteria were assessed for quality. Fourteen articles were identified as eligible to be included in the review. Compared with single-task, two studies reported better motor performance, six reported poorer motor performance, and three reported no difference in motor performance under multitask. Compared with single- task, two studies reported better cognitive performance, seven studies reported poorer cognitive performance, and three studies reported no difference in cognitive performance under multitask. As occupational duties become increasingly demanding, it is crucial to modify and adapt performance assessments to meet the needs required of tactical athletes to guide training and injury management programs. Motor and cognitive assessments are an integral part of performance evaluations to train, prepare, and rehabilitate tactical athletes. To meet the modern demands of tactical athletes, varying levels of difficulty in multitask paradigms that include both motor and cognitive tasks should be investigated to understand fundamental performance under operational settings to better translate across training paradigms and rehabilitation programs.


Severe Bleeding Tendency due to Excessive Fibrinolysis in Two Patients With Aortic Disease: Role of Tranexamic Acid in Non-Surgical Candidate.
Disseminated intravascular coagulation (DIC) is characterized by systemic activation of coagulation pathway which can lead to thrombosis and bleeding. Chronic DIC associated with aortic aneurysm or dissection commonly presents with bleeding symptoms with variable severity due to enhanced fibrinolysis. Patients with unexplained bleeding diathesis with DIC should include aortic disease as one of the differential diagnoses. This paper reports two patients with severe hemorrhagic complications due to aortic disease. Long-term prophylactic treatment is recommended if the underlying aortic disease cannot be surgically managed. Tranexamic acid is a potentially safe option to relieve bleeding tendency.


Dissociative identity disorder: Medicolegal challenges.
Persons with dissociative identity disorder (DID) often present in the criminal justice system rather than the mental health system and perplex experts in both professions. DID is a controversial diagnosis with important medicolegal implications. Defendants have claimed that they committed serious crimes, including rape or murder, while they were in a dissociated state. Asserting that their alter personality committed the bad act, defendants have pleaded not guilty by reason of insanity (NGRI). In such instances, forensic experts are asked to assess the defendant for DID and provide testimony in court. Debate continues over whether DID truly exists, whether expert testimony should be allowed into evidence, and whether it should exculpate defendants for their criminal acts. This article reviews historical and theoretical perspectives on DID, presents cases that illustrate the legal implications and controversies of raising an insanity defense based on multiple personalities, and examines the role of forensic experts asked to comment on DID with the goal of assisting clinicians in the medicolegal assessment of DID in relation to crimes.


If you can't comply with dialysis, how do you expect me to trust you with transplantation? Australian nephrologists' views on indigenous Australians' 'non-compliance' and their suitability for kidney transplantation.
Indigenous Australians suffer markedly higher rates of end-stage kidney disease (ESKD) but are less likely than their non-Indigenous counterparts to receive a transplant. This difference is not fully explained by measurable clinical differences. Previous work suggests that Indigenous Australian patients may be regarded by treating specialists as 'non-compliers', which may negatively impact on referral for a transplant. However, this decision-making is not well understood. The objectives of this study were to investigate: whether Indigenous patients are commonly characterised as 'non-compliers'; how estimations of patient compliance factor into Australian nephrologists' decision-making about transplant referral; and whether this may pose a particular barrier for Indigenous patients accessing transplants. Nineteen nephrologists, from eight renal units treating the majority of Indigenous Australian renal patients, were interviewed in 2005-06 as part of a larger study. Thematic analysis was undertaken to investigate how compliance factors in specialists' decision-making, and its implications for Indigenous patients' likelihood of obtaining transplants. Specialists commonly identified Indigenous patients as both non-compliers and high-risk transplant candidates. Definition and assessment of 'compliance' was neither formal nor systematic. There was uncertainty about the value of compliance status in predicting post-transplant outcomes and the issue of organ scarcity permeated participants' responses. Overall, there was marked variation in how specialists weighed perceptions of compliance and risk in their decision-making. Reliance on notions of patient 'compliance' in decision-making for transplant referral is likely to result in continuing disadvantage for Indigenous Australian ESKD patients. In the absence of robust evidence on predictors of post-transplant outcomes, referral decision-making processes require attention and debate.


Unique-hue stimulus selection using Munsell color chips.
Presented are intra- and inter-observer variability data comparing the unique-hue (UH) selections of sets of males and females, using two different visual experimental procedures incorporating Munsell color chips of varying hue but identical chroma and value. Although 34 of the 40 Munsell hue chips were selected by at least one observer as a UH, selections were generally repeatable. In addition, intra-observer variability represented approximately 15% of inter-observer variability. Also, when only three consecutive Munsell chips were viewed at a time, females showed significantly larger intra-observer variability than males, especially when making unique green selections. However, variability in UH selections was statistically insignificant between males and females when all Munsell chips were viewed simultaneously. No correlation was found between UH selections or intra-observer variability and hue ordering ability.


Neurological disease in wild loggerhead sea turtles Caretta caretta.
Beginning in October 2000, subadult loggerhead sea turtles Caretta caretta showing clinical signs of a neurological disorder were found in waters off south Florida, USA. Histopathology indicated generalized and neurologic spirorchiidiasis. In loggerhead sea turtles (LST) with neurospirorchiidiasis, adult trematodes were found in the meninges of the brain and spinal cord of 7 and 3 affected turtles respectively, and multiple encephalic intravascular or perivascular eggs were associated with granulomatous or mixed leukocytic inflammation, vasculitis, edema, axonal degeneration and occasional necrosis. Adult spirorchiids were dissected from meningeal vessels of 2 of 11 LST brains and 1 of 10 spinal cords and were identified as Neospirorchis sp. Affected LST were evaluated for brevetoxins, ciguatoxins, saxitoxins, domoic acid and palytoxin. While tissues from 7 of 20 LST tested positive for brevetoxins, the levels were not considered to be in a range causing acute toxicosis. No known natural (algal blooms) or anthropogenic (pollutant spills) stressors co-occurred with the turtle mortality. While heavy metal toxicosis and organophosphate toxicosis were also investigated as possible causes, there was no evidence for their involvement. We speculate that the clinical signs and pathologic changes seen in the affected LST resulted from combined heavy spirorchiid parasitism and possible chronic exposure to a novel toxin present in the diet of LST.


Context mitigates crowding: Peripheral object recognition in real-world images.
Object recognition is often conceived of as proceeding by segmenting an object from its surround, then integrating its features. In turn, peripheral vision's sensitivity to clutter, known as visual crowding, has been framed as due to a failure to restrict that integration to features belonging to the object. We hand-segment objects from their background, and find that rather than helping peripheral recognition, this impairs it when compared to viewing the object in its real-world context. Context is in fact so important that it alone (no visible target object) is just as informative, in our experiments, as seeing the object alone. Finally, we find no advantage to separately viewing the context and segmented object. These results, taken together, suggest that we should not think of recognition as ideally operating on pre-segmented objects, nor of crowding as the failure to do so.


Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway.
Acetaminophen (APAP) is a well-known antipyretic and analgesic drug. However, the accidental or intentional APAP overdose will induce liver injury and even acute liver failure. Astragaloside IV (AS-IV), a bioactive compound isolated from Astragali Radix, has been reported to have protective effects on the digestive and immune systems because of its anti-oxidant and anti-inflammatory properties. This study aims to observe whether AS-IV pretreatment provides protection against APAP-induced liver failure. The results of serum alanine/aspartate aminotransferases (ALT/AST) analysis, hepatic glutathione (GSH), and malondialdehyde (MDA) amounts, and liver superoxide dismutase (SOD) activity showed that AS-IV protected against APAP-induced hepatotoxicity. Liver histological observation further evidenced this protection provided by AS-IV. AS-IV was found to reverse the APAP-induced increased amounts of pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). Western-blot analysis showed that AS-IV increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2), and enhanced the expression of heme oxygenase 1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) in the presence of APAP. AS-IV also decreased the expression of kelch-like ECH-associated protein-1 (Keap1). In conclusion, we demonstrated that AS-IV exerted a strong protection against APAP-induced hepatotoxicity by activating Nrf2 antioxidant signaling pathways.


Education of family members to support weaning to solids and nutrition in infants born preterm.
Weaning refers to the period of introduction of solid food to complement breast milk or formula milk. Preterm infants are known to acquire extrauterine growth restriction by the time of discharge from neonatal units. Hence, the postdischarge and weaning period are crucial for optimal growth. Optimisation of nutrition during weaning may have long-term impacts on outcomes in preterm infants. Family members of preterm infants may require nutrition education to promote ideal nutrition practices surrounding weaning in preterm infants who are at high risk of nutritional deficit. To investigate the role of nutrition education of family members in supporting weaning in preterm infants with respect to their growth and neurodevelopment compared with conventional management. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 26 June 2018), Embase (1980 to 26 June 2018), and CINAHL (1982 to 26 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. RCTs and quasi-RCTs were eligible for inclusion if they examined the effects of nutrition education of family members as compared to conventional management for weaning of preterm infants up to one year of corrected gestational age. We defined prematurity as less than 37 completed weeks of gestation. At least two review authors independently screened potential studies for inclusion and planned to identify, extract data, and assess the quality of eligible studies. We resolved any differences in opinion through discussion with a third review author and consensus among all three review authors. No eligible trials looking at the impact of nutrition education of family members in weaning of preterm infants fulfilled the inclusion criteria of this systematic review. Two studies investigating the ideal timing for weaning in premature infants reported conflicting results, AUTHORS' CONCLUSIONS: We were unable to assess the impact of nutrition education of family members in weaning of preterm infants as there were no eligible studies. This may be due to the lack of evidence to determine the ideal weaning strategies for preterm infants with regards to the time of initiating weaning and type of solids to introduce. Trials are needed to assess the many aspects of infant weaning in preterm infants. Long-term neurodevelopment and metabolic outcomes should also be assessed in addition to growth parameters.


Antigenic stimulation and the occurrence of chronic lymphocytic leukemia.
Data from a population-based case-control study of chronic lymphocytic leukemia were analyzed to assess the possible etiologic role of chronic antigenic stimulation. The study, conducted in four geographic areas of the United States (the metropolitan areas surrounding Seattle, Washington, Salt Lake City, Utah, Detroit, Michigan, and Atlanta, Georgia) sought to identify all incident cases (n = 430) among residents diagnosed between July 1, 1977 and December 31, 1981. The responses of these cases to questions about possible sources of antigenic stimulation were compared with the responses of controls selected from the populations of these areas. Little difference between cases and controls was present for a history of most forms of viral and bacterial infection and for a history of allergies or allergy treatment. However, a relation was observed with antecedent syphilis infection (odds ratio (OR) = 5.0, 95% confidence interval (Cl) 2.0-12.9). Associations of smaller magnitude were observed with a history of tuberculosis (OR = 1.9, 95% Cl 1.0-3.7) and of urinary tract infection (OR = 1.4, 95% Cl 1.1-1.9). Overall, however, the authors found little evidence of a relation between chronic antigenic stimulation and the occurrence of chronic lymphocytic leukemia. Nonetheless, because the measure of prior antigenic stimulation was restricted to that obtained through interviews and undoubtedly was an insensitive one, these negative results should not be interpreted as ruling out antigenic stimulation as a possible cause of some cases of chronic lymphocytic leukemia.


Troponin in embryonic chick skeletal muscle cells in vitro. An immunoelectron microscope study.
The fine structurel distribution of troponin on thin filaments in developing myofibrils was investigated by the use of immunoelectron microscopy. Embryonic chick skeletal muscle cells grown in vitro were treated with antibodies against each of the troponin components (troponin T, I, and C) from adult chicken muscles. Each antibody was distributed along the thin filaments with a period of 38 nm. It is concluded that these newly synthesized regulatory proteins are assembled at their characteristic position from the initial phases of myofibrillogenesis.


Mechanistic studies of protein arginine deiminase 2: evidence for a substrate-assisted mechanism.
Citrullination, which is catalyzed by protein arginine deiminases (PADs 1-4 and 6), is a post-translational modification (PTM) that effectively neutralizes the positive charge of a guanidinium group by its replacement with a neutral urea. Given the sequence similarity of PAD2 across mammalian species and the genomic organization of the PAD2 gene, PAD2 is predicted to be the ancestral homologue of the PADs. Although PAD2 has long been known to play a role in myelination, it has only recently been linked to other cellular processes, including gene transcription and macrophage extracellular trap formation. For example, PAD2 deiminates histone H3 at R26, and this PTM leads to the increased transcription of more than 200 genes under the control of the estrogen receptor. Given that our understanding of PAD2 biology remains incomplete, we initiated mechanistic studies on this enzyme to aid the development of PAD2-specific inhibitors. Herein, we report that the substrate specificity and calcium dependence of PAD2 are similar to those of PADs 1, 3, and 4. However, unlike those isozymes, PAD2 appears to use a substrate-assisted mechanism of catalysis in which the positively charged substrate guanidinium depresses the pKa of the nucleophilic cysteine. By contrast, PADs 1, 3, and 4 use a reverse-protonation mechanism. These mechanistic differences will aid the development of isozyme-specific inhibitors.


Usefulness of subjective ovine milk scores: II. Genetic parameter estimates.
Genetic parameters for a subjective milk score given to ewes within 24 h of parturition were estimated to determine the usefulness of milk score as a selection trait to improve milk production, which influences total litter weight weaned. Heritability of milk score and the genetic correlation of milk score with litter weight weaned were estimated by REML separately for four sheep breeds, Rambouillet (n = 1,731), Targhee (n = 1,638), Columbia (n = 1,731), and Polypay (n = 1,129). Litter weight weaned was the total weight of lambs weaned at approximately 120 d of age under a western range production system. Observed heritability estimates for milk score at first parity were moderate and similar among breeds, ranging from 0.18 to 0.32. Heritability estimates adjusted for a binomial distribution of milk scores at first parity were high (Columbia, 0.43; Polypay, 0.35; Rambouillet, 0.50; Targhee, 0.84). Estimates of observed heritability for second-parity milk score were moderate to high, ranging from 0.23 to 0.46. Milk score at first or second parity was genetically correlated with milk score records at maturity (third parity and greater), with estimates ranging from 0.69 to 1.00. Milk score and litter weight weaned were genetically correlated at first or second parity in Rambouillet (r(g) = 1.00) and Targhee breeds (r(g) = 1.00 and 0.61, respectively), but not in the Columbia and Polypay breeds. Estimates of heritability for lifetime records for milk score ranged from 0.16 to 0.26 across breeds. Estimates of genetic correlations of annual lifetime milk score records with litter weight weaned were high (Columbia, 1.00; Polypay, 0.81; Rambouillet, 1.00; and Targhee, 0.77). Repeatability estimates for milk score were similar across breeds, 0.23 for Columbia, Rambouillet, and Targhee ewes and 0.28 for Polypay ewes. Milk score measured at first or second parity may be a good predictor of future potential milking ability. Further, milk score can be used as a selection trait to improve maternal ability for increasing litter weight weaned. The need for increasing ewe milking performance and lamb growth rate at first parity in commercial range sheep production systems may be addressed by selection for milk score at first parity.


Machine learning approach to identify a resting-state functional connectivity pattern serving as an endophenotype of autism spectrum disorder.
Endophenotype refers to a measurable and heritable component between genetics and diagnosis, and the same endophenotype is present in both individuals with a diagnosis and their unaffected siblings. Determination of the neural correlates of an endophenotype and diagnosis is important in autism spectrum disorder (ASD). However, prior studies enrolling individuals with ASD and their unaffected siblings have generally included only one group of typically developing (TD) subjects; they have not accounted for differences between TD siblings. Thus, they could not differentiate the neural correlates for endophenotype from the clinical diagnosis. In this context, we enrolled pairs of siblings with an ASD endophenotype (individuals with ASD and their unaffected siblings) and pairs of siblings without this endophenotype (pairs of TD siblings). Using resting-state functional MRI, we first aimed to identify an endophenotype pattern consisting of multiple functional connections (FCs) then examined the neural correlates of FCs for ASD diagnosis, controlling for differences between TD siblings. Sparse logistic regression successfully classified subjects as to the endophenotype (area under the curve = 0.78, classification accuracy = 75%). Then, a bootstrapping approach controlling for differences between TD siblings revealed that an FC between the right middle temporal gyrus and right anterior cingulate cortex was substantially different between individuals with ASD and their unaffected siblings, suggesting that this FC may be a neural correlate for the diagnosis, while the other FCs represent the endophenotype. The current findings suggest that an ASD endophenotype pattern exists in FCs, and a neural correlate for ASD diagnosis is dissociable from this endophenotype. (250 words).


The relation between self-reported empathy and motor identification with imagined agents.
In a previous study, we found that when required to imagine another person performing an action, participants reported a higher correspondence between their own handedness and the hand used by the imagined person when the agent was seen from the back compared to when the agent was seen from the front. This result was explained as evidence of a greater involvement of motor areas in the back-view perspective, possibly indicating a greater proneness to put oneself in the agent's shoes in such a condition. In turn, the proneness to put oneself in another's shoes could also be considered as a cue of greater identification with the other, that is a form of empathy. If this is the case, the proportion of lateral matches vs mismatches should be different for subjects with high and low self-reported empathy. In the present study, we aimed at testing this hypothesis. Participants were required to imagine a person performing a single manual action in a back view and to indicate the hand used by the imagined person during movement execution. Consistent with our hypothesis, the proportion of matching between the handedness of participants and the handedness of agents imagined was higher for participants scoring high in a self-report measure of empathy. Importantly, this relationship was specific for females. At least for females, our data seem to corroborate the idea of a link between self-reported empathy and motor identification with imagined agents. This sex-specific result is consistent with neuroimaging studies indicating a stronger involvement of action representations during emotional and empathic processing in females than in males. In sum, our findings underline the possibility of employing behavioral research as a test-bed for theories deriving from functional studies suggesting a link between empathic processing and the activation of motor-related areas.


Psychological interventions and the immune system: a meta-analytic review and critique.
This article reviews evidence for the hypothesis that psychological interventions can modulate the immune response in humans and presents a series of models depicting the psychobiological pathways through which this might occur. Although more than 85 trials have been conducted, meta-analyses reveal only modest evidence that interventions can reliably alter immune parameters. The most consistent evidence emerges from hypnosis and conditioning trials. Disclosure and stress management show scattered evidence of success. Relaxation demonstrates little capacity to elicit immune change. Although these data provide only modest evidence of successful immune modulation, it would be premature to conclude that the immune system is unresponsive to psychological interventions. This literature has important conceptual and methodological issues that need to be resolved before any definitive conclusions can be reached.


Antimony leaching from polyethylene terephthalate (PET) plastic used for bottled drinking water.
Antimony is a regulated contaminant that poses both acute and chronic health effects in drinking water. Previous reports suggest that polyethylene terephthalate (PET) plastics used for water bottles in Europe and Canada leach antimony, but no studies on bottled water in the United States have previously been conducted. Nine commercially available bottled waters in the southwestern US (Arizona) were purchased and tested for antimony concentrations as well as for potential antimony release by the plastics that compose the bottles. The southwestern US was chosen for the study because of its high consumption of bottled water and elevated temperatures, which could increase antimony leaching from PET plastics. Antimony concentrations in the bottled waters ranged from 0.095 to 0.521 ppb, well below the US Environmental Protection Agency (USEPA) maximum contaminant level (MCL) of 6 ppb. The average concentration was 0.195+/-0.116 ppb at the beginning of the study and 0.226+/-0.160 ppb 3 months later, with no statistical differences; samples were stored at 22 degrees C. However, storage at higher temperatures had a significant effect on the time-dependent release of antimony. The rate of antimony (Sb) release could be fit by a power function model (Sb(t)=Sb 0 x[Time, h]k; k=8.7 x 10(-6)x[Temperature ( degrees C)](2.55); Sb 0 is the initial antimony concentration). For exposure temperatures of 60, 65, 70, 75, 80, and 85 degrees C, the exposure durations necessary to exceed the 6 ppb MCL are 176, 38, 12, 4.7, 2.3, and 1.3 days, respectively. Summertime temperatures inside of cars, garages, and enclosed storage areas can exceed 65 degrees C in Arizona, and thus could promote antimony leaching from PET bottled waters. Microwave digestion revealed that the PET plastic used by one brand contained 213+/-35 mgSb/kg plastic; leaching of all the antimony from this plastic into 0.5L of water in a bottle could result in an antimony concentration of 376 ppb. Clearly, only a small fraction of the antimony in PET plastic bottles is released into the water. Still, the use of alternative types of plastics that do not leach antimony should be considered, especially for climates where exposure to extreme conditions can promote antimony release from PET plastics.


Clinical Trials Required to Assess Potential Benefits and Side Effects of Treatment of Patients With Anorexia Nervosa With Recombinant Human Leptin.
The core phenotype of anorexia nervosa (AN) comprises the age and stage dependent intertwining of both its primary and secondary (i.e., starvation induced) somatic and mental symptoms. Hypoleptinemia acts as a key trigger for the adaptation to starvation by affecting diverse brain regions including the reward system and by induction of alterations of the hypothalamus-pituitary-"target-organ" axes, e.g., resulting in amenorrhea as a characteristic symptom of AN. Particularly, the rat model activity-based anorexia (ABA) convincingly demonstrates the pivotal role of hypoleptinemia in the development of starvation-induced hyperactivity. STAT3 signaling in dopaminergic neurons in the ventral tegmental area (VTA) plays a crucial role in the transmission of the leptin signal in ABA. In patients with AN, an inverted U-shaped relationship has been observed between their serum leptin levels and physical activity. Albeit obese and therewith of a very different phenotype, humans diagnosed with rare congenital leptin deficiency have starvation like symptoms including hypothalamic amenorrhea in females. Over the past 20 years, such patients have been successfully treated with recombinant human (rh) leptin (metreleptin) within a compassionate use program. The extreme hunger of these patients subsides within hours upon initiation of treatment; substantial weight loss and menarche in females ensue after medium term treatment. In contrast, metreleptin had little effect in patients with multifactorial obesity. Small clinical trials have been conducted for hypothalamic amenorrhea and to increase bone mineral density, in which metreleptin proved beneficial. Up to now, metreleptin has not yet been used to treat patients with AN. Metreleptin has been approved by the FDA under strict regulations solely for the treatment of generalized lipodystrophy. The recent approval by the EMA may offer, for the first time, the possibility to treat extremely hyperactive patients with AN off-label. Furthermore, a potential dissection of hypoleptinemia-induced AN symptoms from the primary cognitions and behaviors of these patients could ensue. Accordingly, the aim of this article is to review the current state of the art of leptin in relation to AN to provide the theoretical basis for the initiation of clinical trials for treatment of this eating disorder.


Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity.
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293). This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.


Phase II design: history and evolution.
Historically, phase II trials in oncology generally had a single-arm design, constructed to distinguish between a tumor response rate felt to indicate a lack of promise (often 5%) and a rate that would indicate potential benefit (often 20%), with a one-sided type I error rate of 5% to 10% and a type II error rate of 10% to 20%. The dominant use of this design was based on the premise that an agent that could not produce a tumor response rate of 20% was not likely to produce a clinically meaningful overall survival (OS) or progression-free survival (PFS) benefit in subsequent phase III testing. Recent trends in oncology drug development have challenged this paradigm. Many phase II trials are now designed to assess the promise of a molecularly targeted agent, given either alone or in combination with another regimen. In many cases these agents are not anticipated to produce or improve tumor response rates; rather the desired outcome from their use is improved PFS or OS through means other than direct cell killing as evidenced by tumor shrinkage. In general, PFS is the preferred end point for such phase II trials, as it is more statistically efficient than OS (because it is substantially shorter and the treatment effect is not diluted by salvage treatment). However, in a situation with no effective salvage therapy and/or a disease with concerns regarding the timing of progression assessment, OS could be chosen as the endpoint. We have reviewed the history and evolution of the phase II trial over the past 50 years, in particular, in oncology trials. This review is not meant to be exhaustive, but rather to cover the primarily used designs in self-contained detail, in such a manner as to provide a primer for the young investigator and reminders for the more experienced.


Media coverage of chronic diseases in the Netherlands.
Little is known about the quantity or quality of information on rheumatic diseases provided by the mass media. The aim of this study was to gain insight into the media coverage of rheumatic diseases compared with other chronic diseases in the Netherlands. Newspaper articles, magazine articles, and medical television programs that appeared or were broadcast during a 1-year period, and contained information on rheumatic diseases, heart disease, cancer, chronic lung disease, or diabetes mellitus, were selected for content analysis. For each article and program, it was determined whether coverage concentrated on treatment, influence of lifestyle, scientific progress, or disease consequences. It was also determined whether professional experts and patients were featured. Nine hundred seventeen newspaper articles, 304 magazine articles, and 163 medical programs were found. Most dealt with cancer (43%) and heart disease (37%). The amount of media attention given to each of the five disease categories was found to correspond with mortality but not with prevalence. The contents of the articles and programs differed significantly according to disease topic. The main focus in rheumatic diseases was on patients' experiences, as well as regular and alternative medications. In heart disease and cancer, the main focus was on professional medical viewpoints, operations, and mortality, whereas in chronic lung disease and diabetes it was on treatments in the context of regular medications, scientific progress, and incurability. The influence of lifestyle on the disease process was mentioned most often in connection with diabetes, rheumatic disease, and chronic lung disease. The amount of attention a disease category received from the media depended on its fatality rates and not on its prevalence. Heart disease and cancer were portrayed as being more serious than the more lingering diseases. Surprisingly, the proportion of articles and programs that included the influence of lifestyle in their coverage was lowest for cancer and heart disease. More frequent and more accurate coverage of chronic diseases, especially rheumatic diseases, is needed if their image is to be brought into line with their importance for and impact on the community.


Semen analysis: looking for an upgrade in class.
To review the literature database regarding current methods for diagnosing male subfertility and to critique new testing methods that have the potential to be incorporated as part of routine semen analysis. Literature database review. None. None. None. None. Methods for performing high quality semen analysis are standardized and clearly presented in the 2010 World Health Organization (WHO) laboratory manual for the examination and processing of human semen. In spite of the fact that lower reference limits contained therein are now evidence-based, debate persists about their clinical value. One test put forth as being additive to the semen analysis is assessment of DNA integrity. However, due to lack of standardized methods and quality control measures, accessibility to instrumentation, and evidence-based reference values for clinical interpretation this test has not become incorporated into the clinical andrology mainstream. Novel tests that probe molecular function have emerged that also have promise for integration into routine clinical semen analysis. Semen analysis, when performed according to WHO guidelines, will yield accurate and precise clinical laboratory data on traditional semen parameters. Due to the biological nature of the specimen in question definitive diagnosis of subfertility and its cause(s) remains enigmatic. Novel tests that may be easily standardized for subsequent multi-center, prospective randomized trials need to be integrated so more meaningful clinical diagnoses can be made.


Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies.
Intellectual disability affects about 1-2% of the general population worldwide, and this is the leading socio-economic problem of health care. The evaluation of the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease. We describe the first Lithuanian experience in genome-wide CNV detection and whole exome sequencing, presenting the results obtained in the research project UNIGENE. The patients with developmental delay/intellectual disability have been investigated (n = 66). Diagnostic screening was performed using array-CGH technology. FISH and real time-PCR were used for the confirmation of gene-dose imbalances and investigation of parental samples. Whole exome sequencing using the next generation high throughput NGS technique was used to sequence the samples of 12 selected families. 14 out of 66 patients had pathogenic copy number variants, and one patient had novel likely pathogenic aberration (microdeletion at 4p15.2). Twelve families have been processed for whole exome sequencing. Two identified sequence variants could be classified as pathogenic (in MECP2, CREBBP genes). The other families had several candidate intellectual disability gene variants that are of unclear clinical significance and must be further investigated for possible effect on the molecular pathways of intellectual disability. The genetic heterogeneity of intellectual disability requires genome wide approaches, including detection of chromosomal aberrations by chromosomal microarrays and whole exome sequencing capable of uncovering single gene mutations. This study demonstrates the benefits and challenges that accompany the use of genome wide molecular technologies and provides genotype-phenotype information on 32 patients with chromosomal imbalances and ID candidate sequence variants.


Identification of a polymorphic nucleotide in oxyR specific for Mycobacterium bovis.
Automated sequence analysis of a 410-bp region of the axyR gene in 105 Mycobacterium tuberculosis complex isolates identified a polymorphic nucleotide that differentiated Mycobacterium bovis isolates from other complex members. All 29 M. bovis isolates sequenced had an adenine residue at nucleotide 285, whereas all 76 other complex isolates had a guanine residue. PCR-restriction fragment length polymorphism analysis of oxyR with restriction endonuclease AluI in an additional 255 complex isolates from widespread intercontinental sources confirmed and extended the unique association of adenine at position 285 with M. bovis isolates.


Asthma due to industrial use of chloramine.
Seven brewery workers developed asthmatic symptoms after using chloramine (chloramine-T) powder as a sterilising agent. They gave positive weal and flare reactions to skin-prick tests with solutions of chloramine at strengths that caused no reactions in unexposed controls. The symptoms did not recur once the men had been removed from areas in which chloramine was handled. As well as causing irritant effects, inhaling dry or liquid aerosols of chloramine may cause sensitisation, with workers being prone to allergic asthma on reexposure. In view of this, measures should be taken to ensure that chloramine is not inhaled.


Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction without Microsurgery Fellowship Training.
Deep inferior epigastric artery perforator (DIEP) flap breast reconstruction requires complex microsurgical skills. Herein, we examine whether DIEP flap breast reconstruction can be performed safely without microsurgical fellowship training. A total of 28 patients and 34 DIEP flaps were included in the study. We reviewed the medical records of patients for donor site and flap-related complications and analyzed the correlation between the complications and preoperative risk factors. We also performed a literature review to compare complication rates in our series with the literature. We observed total flap necrosis in 1 patient (2.9%), partial flap necrosis in 5 patients (14.7%), infection in 1 patient (2.9%), hematoma/seroma in 3 patients (8.8%), donor site complications in 5 patients (18.5%), venous occlusion in 4 patients (11.7%), and arterial occlusion in 1 patient (2.9%). We did not observe any correlation between complications and preoperative risk factors. Literature review yielded 18 papers that met our inclusion criteria. Partial flap necrosis rate was significantly higher in our series compared with literature (14.7% vs 1.6%, P = 0.003). Venous complication rate was marginally higher in our series compared with literature (11.7% vs 3.3%, P = 0.057). However, total flap loss rate in our series was comparable with the literature (2.9% vs 2.2%, P = 0.759). With proper training during plastic surgery residency, DIEP flap can be performed with acceptable morbidity.


Fibroblasts as novel therapeutic targets in chronic inflammation.
A characteristic feature of many chronic inflammatory diseases is their persistence and predilection for certain sites. The molecular basis for such tissue tropism and failure of the inflammatory response to resolve has until relative recently remained obscure. Recent studies have strongly implicated fibroblasts as cells which contribute to disease persistence and which help define anatomical location. Therefore fibroblasts make an attractive therapeutic target as they help orchestrate the inflammatory infiltrate. Current anti-inflammatory therapies target immune cells in an attempt to inhibit the production of pro-inflammatory mediators. However an equally important target is the active induction of pro-resolution programmes responsible for the resolution of inflammation. Fibroblasts are likely to be an important source of these anti-inflammatory mediators. Therapeutic manipulation of fibroblasts and their biologically active products is an emerging concept in treating cancer and is likely to provide a novel method to achieve improved control of chronic inflammatory disease.


Haloplanus vescus sp. nov., an extremely halophilic archaeon from a marine solar saltern, and emended description of the genus Haloplanus.
An extremely halophilic archaeon, strain RO5-8T, was isolated from a disused marine solar saltern in China. The cells were pleomorphic and flat. In static liquid medium, cells floated to the surface. Strain RO5-8T stained Gram-negative and colonies were pink-pigmented. It was able to grow at 30-50 degrees C (optimum 40 degrees C), at 2.6-4.3 M NaCl (optimum 3.1 M NaCl), at 0.03-0.5 M MgCl2 (optimum 0.03 M MgCl2) and at pH 5.5-7.5 (optimum pH 6.0-6.5). Cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 12% (w/v). The major polar lipids of strain RO5-8T were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and one major glycolipid chromatographically identical to the sulfated mannosyl glucosyl diether S-DGD-1. On the basis of 16S rRNA gene sequence analysis, strain RO5-8T was closely related to three strains of Haloplanus natans with similarities of 97.3-97.6%. The DNA G+C content of strain RO5-8T was 62.1 mol%. The DNA-DNA hybridization value between strain RO5-8T and Haloplanus natans JCM 14081T was 51.6%. It was concluded that strain RO5-8T represents a novel species of the genus Haloplanus, for which the name Haloplanus vescus sp. nov. is proposed. The type strain is RO5-8T (=CGMCC 1.8712T =JCM 16055T).


Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma.
For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC. With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors. The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed ≥5% and >25% GPNMB positive tumor cells, respectively. This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients.


Correspondence of physical activity and fruit/vegetable consumption among prostate cancer survivors and their spouses.
A healthy diet and physical activity are recommended for prostate cancer survivors. Interdependence theory suggests that the spousal relationship influences those health behaviours and the degree of correspondence may be an indicator of this influence. This study evaluated the correspondence between prostate cancer survivors and spouses regarding physical activity and fruit/vegetable consumption. Baseline data from an ongoing randomised control trial were utilised. Men who had been treated for prostate cancer within the past year and their partners (N = 132 couples) completed self-report measures of physical activity, fruit/vegetable consumption, relationship satisfaction and support for partner's healthy diet and physical activity. Couples reported similar fruit/vegetable consumption and physical activity as indicated by high levels of correspondence. Greater fruit/vegetable correspondence was related to higher relationship satisfaction (F = 4.14, P = 0.018) and greater patient (F = 13.29, P < 0.001) and spouse-rated support (F = 7.2, P < 0.001). Greater physical activity correspondence was related to greater patient (F = 3.57, P = 0.028) and spouse-rated support (F = 4.59, P = 0.031). Prostate cancer survivors and spouses may influence each other's diet and exercise behaviours. Couple-based interventions may promote healthy behaviours among this population.


Microglia contribute to ammonia-induced astrocyte swelling in culture.
Brain edema, a lethal complication of acute liver failure (ALF), is believed to be largely cytotoxic due to the swelling of astrocytes. Ammonia, a principal neurotoxin in ALF, has been strongly implicated in the development of the brain edema. It was previously shown that treatment of cultured astrocytes with ammonia (5 mM NH₄Cl) results in cell swelling. While ammonia continues to exert a direct effect on astrocytes, it is possible that ammonia can affect other neural cells, particularly microglia. Microglia are capable of evoking an inflammatory response, a process known to contribute to the brain edema. We therefore examined the potential role of microglia in the mechanism of ammonia-induced astrocyte swelling. Conditioned media (CM) derived from ammonia-treated cultured microglia when added to cultured astrocytes resulted in significant cell swelling. Such swelling was synergistically increased when astrocytes were additionally treated with 5 mM ammonia. CM from ammonia-treated microglia also showed significant release of oxy-radicals and nitric oxide into the CM. CM from ammonia-treated microglia containing Tempol (a superoxide scavenger) or uric acid (a peroxynitrite scavenger) when added to astrocytes resulted in marked reduction in the cell swelling. Together, these studies indicate that microglia contribute to the ammonia-induced astrocyte swelling by a mechanism involving oxidative/nitrosative stress.


User perspective of DITIS: virtual collaborative teams for home-healthcare.
DITIS supports home-care by offering wireless health care services for chronic illnesses. The main service is the dynamic creation, management and co-ordination of virtual collaborative healthcare teams for the continuous treatment of the patient at home, independently of the physical location of the team's members (or the patient). For each patient a flexible (dynamic) virtual medical team is provided, made up from visiting home-care nurses, doctors, and other health care professionals, responsible for each case. This virtual team is able to provide dedicated, personalized and private service to the home residing patient on a need based and timely fashion, under the direction of the treating specialist, without the necessity to move the patient from his home, thus making better use of the scarce and expensive medical professionals and scarce hospital beds, irrespective of geographic or organisational barriers. DITIS uses a number of state of the art technologies which are seamlessly put together, such as collaboration and personalization via mobile agents, access to medical data from anywhere and any time via a variety of mobile devices and a variety of protocols (i.e., WAP, HTML) and continuous connectivity via new communication technologies such as ADSL and GPRS, and soon UMTS. All the technologies are selected for platform independence.


Can male circumcision have an impact on the HIV epidemic in men who have sex with men?
Three trials have demonstrated the prophylactic effect of male circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions are underway throughout sub-Saharan Africa. Similar efforts for men who have sex with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV easily through receptive sex and transmit easily through insertive sex. Existing work suggests that MC for MSM should reach its maximum potential in settings where sexual role segregation is historically high and relatively stable across the lifecourse; HIV incidence among MSM is high; reported willingness for prophylactic circumcision is high; and pre-existing circumcision rates are low. We aim to identify the likely public health impact that MC interventions among MSM would have in one setting that fulfills these conditions-Peru-as a theoretical upper bound for their effectiveness among MSM generally. We use a dynamic, stochastic sexual network model based in exponential-family random graph modeling and parameterized from multiple behavioral surveys of Peruvian MSM. We consider three enrollment criteria (insertive during 100%, >80% or >60% of UAI) and two levels of uptake (25% and 50% of eligible men); we explore sexual role proportions from two studies and different frequencies of switching among role categories. Each scenario is simulated 10 times. We estimate that efficiency could reach one case averted per 6 circumcisions. However, the population-level impact of an optimistic MSM-MC intervention in this setting would likely be at most ∼5-10% incidence and prevalence reductions over 25 years. Roll-out of MC for MSM in Peru would not result in a substantial reduction in new HIV infections, despite characteristics in this population that could maximize such effects. Additional studies are needed to confirm these results for other MSM populations, and providers may consider the individual health benefits of offering MC to their MSM patients.


[Anisotropy in depth perception of photograph].
How can we reproduce real physical depth from a photograph? How does depth perception in the photograph differ from depth perception in the direct observation? In Experiment 1, objects in an open space were photographed and presented on a screen. Subjects were asked to judge the distances from a fixed point to the objects and the angles from the median line. The distances and the angles in the photograph were perceived shorter and larger than in physical space, respectively. Furthermore, depth perception in the photograph had an anisotropic property. In Experiment 2, the same objects as in Experiment 1 were observed directly by the subjects. The distances and the angles in the direct observation were perceived longer and smaller at longer distance than in the photograph, respectively. It was concluded that depth perception in the photograph did not reproduce depth either in physical space or in visual space, but it was closer to depth in visual space than in physical space. Furthermore, photographic space had an anisotropic property as visual space did.


Molecular mass and dynamics of poly(methyl acrylate) in the glass-transition region.
The segmental dynamics of bulk poly(methyl acrylate) (PMA) were studied as a function of molecular mass in the glass-transition region using 2H NMR and modulated differential scanning calorimetry (MDSC). Quadrupole-echo 2H NMR spectra were obtained for four samples of methyl-deuterated PMA-d3 with different molecular masses. The resulting spectra were fit using superpositions of simulated spectra generated from the MXQET simulation program, based on a model incorporating nearest-neighbor jumps from positions on the vertices of a truncated icosahedron (soccer-ball shape). The lower molecular-mass samples, influenced by the presence of more chain ends, showed more heterogeneity (broader distribution) and lower glass transitions than the higher molecular-mass samples. The MDSC experiments on both protonated and deuterated samples showed behavior consistent with the NMR results, but temperature shifted due to the different frequency range of the measurements in terms of both the position and breadth of the glass transition as a function of molecular mass.


Potential water quality changes due to corn expansion in the Upper Mississippi River Basin.
While biofuels may yield renewable fuel benefits, there could be downsides in terms of water quality and other environmental stressors, particularly if corn is relied upon exclusively as the feedstock. The consequences of increased corn production will depend importantly on where (and how) the additional corn is grown, which, in turn, depends on the characteristics of land and its associated profitability. Previous work has relied on rules of thumb for allocating land to increased acreage based on historical land use or other heuristics. Here, we advance our understanding of these phenomena by describing a modeling system that links an economics-driven land use model with a watershed-based water quality model for the Upper Mississippi River Basin (UMRB). This modeling system is used to assess the water quality changes due to increased corn acreage, which is associated with higher relative corn prices. We focus on six scenarios based on six realistic pairs of corn and soybean prices which correspond to a scale of decreasing soybean to corn price ratio. These price-driven land use changes provide estimates of the water quality effects that current biofuel policies may have in the UMRB. Our analysis can help evaluate the costs and environmental consequences associated with implementation strategies for the biofuel mandates of the new energy bill. The amounts of total N and P delivered to the outlet of the UMRB (located at Grafton, Illinois, USA) rise as corn production becomes more intensive in the region. Our results indicate that a 14.4% in corn acreage in the watershed due to corn intensification in the most economically profitable locations would result in a 5.4% increase in total nitrogen loads and in a 4.1% increase in total phosphorus loads at Grafton. Our most aggressive scenario, driven by high but not out of reach crop prices, results in about a 57% increase in corn acreage with a corresponding 18.5% increase in N and 12% increase in P. These are somewhat conservative increases in nutrients, compared to those of previous studies, likely due to our focus on cultivated cropland which is already heavily fertilized.


Effects of labetalol on systemic and pulmonary haemodynamics at rest and during exercise in hypertensive patients.
1. Labetalol was administered to 18 hypertensive patients for an average duration of 2.44 weeks, with an average final daily dose of 1.65 g. 2. Labetalol decreased resting heart rate by 16% and maximal exercise heart rate by 21%; the phenylephrine-induced rise of systolic brachial artery pressure was reduced by 36%. 3. During labetalol brachial artery pressure was lowered by 29/15 mmHg in the recumbent position, by 41/23 mmHg at rest sitting, and by 53/23 mmHg at maximal exercise; total peripheral resistance was not significantly affected at rest recumbent, but was reduced at sitting and at exercise; cardiac output decreased in all conditions. 4. Labetalol reduced mean pulmonary artery and capillary wedge pressures only in the sitting position. Pulmonary vascular resistance remained unchanged. 5. The drug produced significant decreases of plasma renin activity and of plasma aldosterone concentration.