The efficacy of hesperidin for treatment of acute otitis media.
In this experimental study, the effect of hesperidin on the treatment of acute otitis media (AOM) was investigated in an AOM-induced rat model. In total, 35 rats were randomly divided into the following five groups (n=7): group 1 (control), group 2 (AOM with no treatment), group 3 (AOM+antibiotic), group 4 (AOM+hesperidin), and group 5 (AOM+hesperidin+antibiotic). On day 14, group 3,4 and 5 rats were given antibiotic and hesperidin via gavages, respectively. Histopathological and immunological analyses were performed and the results analyzed. Serum levels of TNF-α, IL-4, IL-6 and IL-1β were significantly decreased in the hesperidin- and antibiotic-treated groups compared to the AOM group. The AOM+antibiotic and AOM+hesperidin groups demonstrated reduced histological damage compared to the AOM group. Between the AOM+antibiotic and AOM+hesperidin groups, significant differences in tympanic membrane thickness(ThicTM), inflammation(Inf), and sclerosis(Sc) values were observed. However, no difference in epithelial damage(DamEpith), was seen between the two groups. There was a significant difference in the AOM+antibiotic and AOM+antibiotic+hesperidin groups compared to AOM group (P<0.001). In this study, we observed that both antibiotic and hesperidin treatment reduced AOM symptoms in an AOM-induced rat model. The values in AOM+antibiotic+hesperidin group were markedly lower than those of the other groups. From our results, we propose that hesperidin, in combination with antibiotics, may provide a successful alternative treatment for AOM compared with antibiotics used alone.


On the use of dynamic Bayesian networks in reconstructing functional neuronal networks from spike train ensembles.
Coordination among cortical neurons is believed to be a key element in mediating many high-level cortical processes such as perception, attention, learning, and memory formation. Inferring the structure of the neural circuitry underlying this coordination is important to characterize the highly nonlinear, time-varying interactions between cortical neurons in the presence of complex stimuli. In this work, we investigate the applicability of dynamic Bayesian networks (DBNs) in inferring the effective connectivity between spiking cortical neurons from their observed spike trains. We demonstrate that DBNs can infer the underlying nonlinear and time-varying causal interactions between these neurons and can discriminate between mono- and polysynaptic links between them under certain constraints governing their putative connectivity. We analyzed conditionally Poisson spike train data mimicking spiking activity of cortical networks of small and moderately large size. The performance was assessed and compared to other methods under systematic variations of the network structure to mimic a wide range of responses typically observed in the cortex. Results demonstrate the utility of DBN in inferring the effective connectivity in cortical networks.


Efficacy and effectiveness of online cognitive behavioral treatment: a decade of interapy research.
Since 1996, researchers of the Interapy research group of the University of Amsterdam have been examining the effects of online cognitive behavioral treatment (online CBT). Over the years, the group conducted nine controlled trials of online CBT for a variety of mental health disorders, among a total of 840 participants. These studies suggest that online CBT is a viable and effective alternative to face-to-face treatment. Treatment adherence was 82%, and reductions in psychopathology represented a large between-group effect size of SMD = 0.9 (95% CI: .7 to 1.1), which was maintained over long periods. The research culminated in the foundation of the Interapy clinic, which received Dutch health regulatory body approval in 2005. Since then, costs of online CBT are reimbursed through public health insurance. A large study of the treatment outcome of 1,500 patients of the Interapy clinic showed that effects in clinical practice are similar to those observed in the controlled trials, and comparable to selected benchmarks of naturalistic studies of face-to-face CBT. The accumulated evidence provides compelling support for the efficacy and effectiveness of online CBT.


Dynamic line-by-line pulse shaping with GHz update rate.
We introduce a novel scheme for dynamic line-by-line pulse shaping with GHz update rates. Four lines of an optical frequency comb source are used to injection-lock four individual VCSEL, which are subsequently electrically modulated at 0.4 to 1 GHz through current modulation. This concept could be considered a completely new way of pulse shaping as the light is not simply modified, but rather regenerated with the desired properties. We also discuss an important drawback of line-by-line pulse shapers that ultimately limits the modulation speed capability.


Predicting cardiovascular disease morbidity and mortality in chronic kidney disease in Spain. The rationale and design of NEFRONA: a prospective, multicenter, observational cohort study.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk (reverse epidemiology effect) and the presence of emerging risk factors specifically related to kidney failure. Therefore, diagnostic tools capable of improving cardiovascular risk assessment beyond traditional risk factors are currently warranted. We present the protocol of a 4-year prospective study aimed to assess the predictive value of non-invasive imaging techniques and biomarkers for CVD events and mortality in patients with CKD. From November 2009 to October 2010, 4137 asymptomatic adult patients with stages 2 to 5 CKD will be recruited from nephrology services and dialysis units throughout Spain. During the same period, 843 participants without CKD (control group) will be recruited from lists of primary care physicians, only at baseline. During the follow-up, CVD events and mortality will be recorded from all CKD patients. Clinical and laboratory characteristics will be collected in a medical documentation sheet. Three trained itinerant teams will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and measurement of ankle-brachial index. In CKD patients, presence and type of calcifications will be assessed in the wall of carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. From all participants, blood samples will be collected and stored in a biobank to study novel biomarkers. The NEFRONA study is the first large, prospective study to examine the predictive value of several non-invasive imaging techniques and novel biomarkers in CKD patients throughout Spain. Hereby, we present the protocol of this study aimed to explore the most effective way in which these tests can be integrated with traditional risk factors to maximize CVD detection in this population.


Functional Foods and Nondairy Probiotic Food Development: Trends, Concepts, and Products.
Recently, the focus of scientific investigations has moved from the primary role of food as the source of energy and body-forming substances to the more subtle action of biologically active food components on human health. There has been an explosion of consumer interest in the active role of food in the well-being and life prolongation, as well as in the prevention of initiation, promotion, and development of nontransmissible chronic diseases. As a result, a new term-functional food-was proposed. Among these foods, probiotics may exert positive effects on the composition of gut microbiota and overall health, and the market is increasing annually. An increased demand for nondairy probiotic products comes from vegetarianism, milk cholesterol content, and lactose intolerance. Therefore, the development of these products is a key research priority for food design and a challenge for both industry and science sectors. This article presents an overview of functional food development, emphasizing nondairy foods that contain probiotic bacteria strains.


Relationship between the pharmacokinetics of levosimendan and its effects on cardiovascular system.
Levosimendan, a Ca(2+) sensitizer, has emerged as an alternative option of pharmacologic inotropic support in patients with decompensated heart failure. In contrast to classic inotropes, rather than interfering with intracellular Ca(2+) levels in myocytes, levosimendan improves cardiac performance via Ca(2+) sensitization and K(+) channel-mediated peripheral vasodilatation. A two compartment pharmacokinetic model with zero-order input and first-order elimination has been found to describe best the pharmacokinetics of levosimendan. Although oral levosimendan has high bioavailability (approximately equal to 85%), in clinical practice it has been hitherto administered intravenously. Levosimendan has total clearance 175-250 mL/h/kg and most importantly a short half-life (about 1.5 hours). Therefore, this drug has a special pharmacokinetic interest: It is one of the few drugs used in cardiovascular medicine, whose prolonged action is not due to the drug itself but it is mainly due to its active metabolite OR-1896 (approximately 80 hours half life). Other metabolites with possible pharmacologic effect are N-conjugated OR-1855 (M7), N-hydroxylated OR-1855 (M8), N-hydroxylated OR-1896 (M10), O-glucuronide OR-1896 (M9) and O-sulfate (M11) of N-hydroxylated OR-1896. Initial reports on levosimendan's use in severe heart failure were positive and levosimendan has already been routinely used for the treatment of patients with decompensated heart failure, while it has been included to the European Society of Cardiology guidelines for the treatment of acute heart failure (class of recommendation IIb, level of evidence B). However, recent clinical trials have failed to demonstrate a clear benefit of levosimendan on survival, compared to other classic inotropic agents in patients requiring inotropic support. In this review article we provide a pharmacokinetic approach for the use of levosimendan in cardiovascular system by discussing its metabolism and mainly the pharmacology of its active metabolites in humans.


Strengthening data collection for neglected tropical diseases: What data are needed for models to better inform tailored intervention programmes?
Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increasingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.


Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific.
RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen. It has been shown to induce significant protection to challenge infection with a homologous parasite strain in American volunteers. In a recently completed trial in semi-immune Gambian adults, vaccine efficacy against natural infection was 34% (95% confidence interval = 8-53%, P = 0.014) during the malaria season following vaccination. Breakthrough P. falciparum parasites sampled from vaccinated subjects and from controls were genotyped at two polymorphic regions of the csp gene encoding T cell epitopes (csp-th2r and csp-th3r) to determine if the vaccine conferred a strain-specific effect. The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls.


Density and the commitment of apical meristems to clonal growth and reproduction in Hieracium pilosella.
We examined responses to population density in the commitment of apical meristems to reproduction and clonal growth in a rosette-forming, stoloniferous herb (Hieracium pilosella). Despite close physiological coupling between the evocation of the terminal inflorescence bud and the development of one or more axillary buds into stolons, the allocation of meristems was extremely plastic.Genets at the higher sowing densities showed density-dependent mortality consistent with self-thinning along a-3/2 trajectory. The probability of inflorescence evocation and associated stolon development was negatively dependent on surviving density. The proportinal distribution of primary stolons amongst genets became strikingly more unequal (expressed as the Gini coefficient) with increasing density. Clonal growth was resolved into the number of primary stolons per stoloniferous genet and the extent of stolon branching (i.e. number of apices per primary stolon); both showed strongly negative density-dependence. Reproduction, expressed as the mean number of flowering capitula per stoloniferous genet, declined 15-fold with increasing density; although theoretically expected to be unity, greater values resulted from capitulum production by attached secondary rosettes and lower values reflected the increasing abortion rate of inflorescence buds with increasing density.Both the total number of apices produced per unit area and the corresponding number of reproductive apices were maximal at intermediate surviving densities (700-1,000 m-2). The balance between reproductive and clonal growth may be expressed as the probability of an apical meristem producing a capitulum, that also peaked sharply at intermediate density. This finding does not conform with linear models that predict a shift from vegetative growth to sexual reproduction with increasing population density.


Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is mediated by transcriptional and post-transcriptional mechanisms.
We investigated the mechanism of thyroid hormone regulation of osteocalcin (OC) gene expression in osteoblast-like cells (ROS 17/2.8). Treatment with tri-iodothyronine (T3) (10(-8) M) increased OC mRNA levels by approximately 3-fold after 24 h and reached a maximum, approximately 5.4-fold, after 48 h. The mRNA levels of other bone-specific genes, alkaline phosphatase and osteopontin, were not affected by T3 treatment. Interestingly, T3 induction of OC mRNA varied according to cell density: approximately 4-fold at approximately 1x10(5) cells/dish and 1.5-fold at 40-60x10(5) cells/dish. The magnitude of OC mRNA induction by T3 was approximately 40% lower than induction by 1,25 dihydroxyvitamin D3 (1,25D3) alone, and the combination of T3+1,25D3 did not further stimulate OC mRNA levels. T3 induction of OC mRNA was not affected by treatment with cycloheximide (10 microg/ml) for 5 h indicating that new protein synthesis is not required for the response. To study the half-life of OC mRNA, ROS 17/2.8 cells were incubated with actinomycin D. The basal half-life of OC mRNA (means+/-s.e.m.) was 6.4+/-0.2 h which was increased significantly with either T3 or 1,25D3 treatment to 10.9+/-0.6 h and 13.5+/-0.4 h respectively. T3 modestly up-regulated the rate of OC gene transcription (1.7+/-0.2-fold) as determined by run-off assay. T3 did not induce a reporter construct containing the rat OC gene (rOC) 5'-flanking region (to -1750 bp) or the previously described rOC vitamin D response element, when transfected into ROS 17/2.8 cells. In conclusion, T3 up-regulates the OC mRNA expression in ROS 17/2.8 cells in a dose-, time- and cell confluence-dependent fashion, and does so by transcriptional and post-transcriptional mechanisms. The greater T3 induction of OC expression in ROS 17/2.8 cells at low cell density is consistent with findings of thyroid hormone action on bone development.


Pulse wave transit time during exercise testing reflects the severity of heart disease in cardiac patients.
The pulse wave transit time (PWTT) is easily measured as the time from the R wave of an electrocardiogram to the arrival of the pulse wave measured by an oxygen saturation monitor at the earlobe. We investigated whether the change of PWTT during exercise testing reflects cardiopulmonary function. Eighty-nine cardiac patients who underwent cardiopulmonary exercise testing (CPX) were enrolled. We analyzed the change of PWTT during exercise and the relationship between the shortening of the PWTT and CPX parameters. PWTT was significantly shortened from rest to peak exercise (204.6 ± 33.6 vs. 145.6 ± 26.4 msec, p < 0.001) in all of the subjects. The patients with heart failure had significantly higher PWTT at peak exercise than the patients without heart failure (152.7 ± 27.1 vs. 140.4 ± 24.8 msec, p = 0.031). The shortening of PWTT from rest to peak exercise showed significant positive correlations with the peak O2 uptake (VO2) (r = 0.56, p < 0.001), anaerobic threshold (r = 0.40, p = 0.016), and % increase of systolic blood pressure during exercise (r = 0.75, p < 0.001), and a negative correlation with the slope of the increase in ventilation versus the increase in CO2 output (VE-VCO2 slope) (r = - 0.42, p = 0.010) in the patients with heart failure. PWTT was shortened during exercise as the exercise intensity increased. In the patients with heart failure, the shortening of PWTT from rest to peak exercise was smaller in those with lower exercise capacity and those with higher VE-VCO2 slope, an established index known to reflect the severity of heart failure.


Global health funding: how much, where it comes from and where it goes.
Global health funding has increased in recent years. This has been accompanied by a proliferation in the number of global health actors and initiatives. This paper describes the state of global heath finance, taking into account government and private sources of finance, and raises and discusses a number of policy issues related to global health governance. A schematic describing the different actors and three global health finance functions is used to organize the data presented, most of which are secondary data from the published literature and annual reports of relevant actors. In two cases, we also refer to currently unpublished primary data that have been collected by authors of this paper. Among the findings are that the volume of official development assistance for health is frequently inflated; and that data on private sources of global health finance are inadequate but indicate a large and important role of private actors. The fragmented, complicated, messy and inadequately tracked state of global health finance requires immediate attention. In particular it is necessary to track and monitor global health finance that is channelled by and through private sources, and to critically examine who benefits from the rise in global health spending.


Comparing Population-based Risk-stratification Model Performance Using Demographic, Diagnosis and Medication Data Extracted From Outpatient Electronic Health Records Versus Administrative Claims.
There is an increasing demand for electronic health record (EHR)-based risk stratification and predictive modeling tools at the population level. This trend is partly due to increased value-based payment policies and the increasing availability of EHRs at the provider level. Risk stratification models, however, have been traditionally derived from claims or encounter systems. This study evaluates the challenges and opportunities of using EHR data instead of or in addition to administrative claims for risk stratification. This study used the structured EHR records and administrative claims of 85,581 patients receiving outpatient care at a large integrated provider system. Common data elements for risk stratification (ie, age, sex, diagnosis, and medication) were extracted from outpatient EHR records and administrative claims. The performance of a validated risk-stratification model was assessed using data extracted from claims alone, EHR alone, and claims and EHR combined. EHR-derived metrics overlapped considerably with administrative claims (eg, number of chronic conditions). The accuracy of the model, when using EHR data alone, was acceptable with an area under the curve of ∼0.81 for hospitalization and ∼0.85 for identifying top 1% utilizers using the concurrent model. However, when using EHR data alone, the predictive model explained a lower amount of variation in utilization-based outcomes compared with administrative claims. The results show a promising performance of models predicting cost and hospitalization using outpatient EHR's diagnosis and medication data. More research is needed to evaluate the benefits of other EHR data types (eg, lab values and vital signs) for risk stratification.


Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome.
The genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Cardiac progenitor cells (CPCs) were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2 transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the NKX2-5 promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex transcriptional and epigenetic mechanisms, at least in part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that coordinately contribute to cardiac malformations in HLHS.


Assessment of nucleotide excision repair XPD polymorphisms in the peripheral blood of gemcitabine/cisplatin-treated advanced non-small-cell lung cancer patients.
Only about one third of non-small-cell lung cancer (NSCLC) patients respond to cisplatin-based chemotherapy. Cisplatin DNA adducts are commonly repaired through the nucleotide excision repair pathway. The study of rare inherited disorders such as xeroderma pigmentosum and Cockayne syndrome has disclosed that XP genes, including XPD, play an essential role in DNA repair, both in the global genomic repair and in the transcription-coupled repair pathways. XPD polymorphism and decreased expression of XP genes have both been linked to lower DNA repair capacity. ERCC1 overexpression has been associated with cisplatin resistance, and experimental evidence shows a close association between ERCC1 and XPD. In the present study, we have examined XPD polymorphisms at codons 751 and 312 in DNA isolated from peripheral blood in 39 patients with gemcitabine/cisplatin-treated locally advanced non-small-cell lung cancer Although no significant correlation was observed between XPD genotype and objective response, a trend toward better response was observed in patients with XPD polymorphism at codon 312. The map of the nucleotide excision repair pathway can be used to design translational research studies to identify and validate predictive markers of response to cisplatin, and the Spanish Lung Cancer Group has recently accrued 250 gemcitabine/cisplatin-treated NSCLC patients for a prospective assessment of XPD genotype


Herd turnover rate reexamined: a tool for improving profitability, welfare, and sustainability.
Longevity and herd turnover rate are becoming common topics of discussion as the dairy industry strives for continuous improvement in efficiency, profitability, animal welfare, and environmental sustainability. Having the most productive animal fill each slot on a dairy makes strategic replacement and the resulting herd turnover an important tool for producers. Dairy operations can be considered to have slots available to be occupied by cows. The number of slots available is governed by dairy characteristics including parlor size and facility design. With sustainability and profitability goals, producers should aim to fill each slot with the most productive animal. The advantages of a modest surplus of replacement heifers allowing for a higher herd turnover rate are examined and shown to improve herd profitability, enhance welfare, and reduce environmental impact. A model assuming constant demand for dairy foods is presented with increased herd turnover rate leading to more milk production per cow and reduced enteric methane emissions. This analysis demonstrates that all else being equal, raising more replacements (having a relatively higher herd turnover rate and decreased herd-level longevity) improves sustainability compared to management aimed at lower herd turnover rates. Understanding the drivers of herd turnover in dairy production has important implications for the components of one health: animal well-being, food production, and environmental stewardship. The present work examines one tool toward this goal, while the companion Currents in One Health by Nguyen et al, JAVMA, January 2023, takes a broader view of many aspects of dairy sustainability.


Early prediction of response to chemotherapy and survival in malignant pleural mesothelioma using a novel semiautomated 3-dimensional volume-based analysis of serial 18F-FDG PET scans.
The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma. Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured. Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival. Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.


Predictive value of absolute CD4 cell count for disease progression in untreated HIV-1-infected children.
To describe the relationship between absolute CD4 cell count and the short-term risk of disease progression in HIV-1-infected children. A meta-analysis of individual longitudinal data on HIV-1-infected children enrolled in trials and cohort studies in Europe and the USA. The risks of progression to death and AIDS (or death) within 12 months, in terms of age and the most recent CD4 cell count, were estimated using parametric survival models. The analysis was restricted to measurements before the start of antiretroviral therapy except zidovudine monotherapy. The values of the absolute CD4 cell count and percentage predicting selected levels of disease progression risk were determined from this and previous models. A total of 566 deaths was observed over 9128 person-years of follow-up, and 992 children progressed to AIDS or death over 7309 person-years of follow-up. In children older than 4 or 5 years, the estimated risk of disease progression increased sharply when the CD4 cell count fell below 200-300 cells/microl. As with other immunological markers, CD4 cell count was less prognostic in younger children. The CD4 cell count values predicting a 12-month risk of death of 2-5% and of AIDS of 5-10% were much more strongly influenced by age than equivalent CD4 cell percentage values. This study suggests it may be appropriate to extend CD4 cell count criteria for initiating antiretroviral therapy in HIV-1-infected adults to children as young as 4 or 5 years. Monitoring by CD4 cell count in younger children is problematical because age is a highly influential variable.


Arginine N-methyltransferase 1 is required for early postimplantation mouse development, but cells deficient in the enzyme are viable.
Protein arginine N-methyltransferases have been implicated in a variety of processes, including cell proliferation, signal transduction, and protein trafficking. In this study, we have characterized essentially a null mutation induced by insertion of the U3betaGeo gene trap retrovirus into the second intron of the mouse protein arginine N-methyltransferase 1 gene (Prmt1). cDNAs encoding two forms of Prmt1 were characterized, and the predicted protein sequences were found to be highly conserved among vertebrates. Expression of the Prmt1-betageo fusion gene was greatest along the midline of the neural plate and in the forming head fold from embryonic day 7.5 (E7.5) to E8.5 and in the developing central nervous system from E8.5 to E13.5. Homozygous mutant embryos failed to develop beyond E6.5, a phenotype consistent with a fundamental role in cellular metabolism. However, Prmt1 was not required for cell viability, as the protein was not detected in embryonic stem (ES) cell lines established from mutant blastocysts. Low levels of Prmt1 transcripts (approximately 1% of the wild-type level) were detected as assessed by a quantitative reverse transcription-PCR assay. Total levels of arginine N-methyltransferase activity and asymmetric N(G), N(G)-dimethylarginine were reduced by 85 and 54%, respectively, while levels of hypomethylated substrates were increased 15-fold. Prmt1 appears to be a major type I enzyme in ES cells, and in wild-type cells, most substrates of the enzyme appear to be maintained in a fully methylated state.


The impact of routine infant immunization with Haemophilus influenzae type b conjugate vaccine in Malawi, a country with high human immunodeficiency virus prevalence.
Malawi has extreme poverty and a high-human immunodeficiency virus (HIV) prevalence. Following Haemophilus influenzae type b (Hib) conjugate vaccine introduction during 2002, we evaluated vaccine impact by reviewing hospital surveillance data for acute bacterial meningitis in Blantyre district among children age 1-59 months admitted during 1997-2005. Documented annual Hib meningitis incidence rates decreased from 20-40/100,000 to near zero among both rural and urban residents despite no change in pneumococcal meningitis incidence rates. Before vaccine introduction, an average of 10 children/year had Hib meningitis and HIV infection compared to 2/year during 2003-2004 and none during 2005. Vaccine effectiveness was high following two or more doses of vaccine. The most urgent future need is for a sustainable routine infant immunization program, including a less expensive vaccine that preferably is delivered in a multivalent form.


Extra-pair paternity in the long-tailed finch Poephila acuticauda.
Although the majority of passerine birds are socially monogamous, true genetic monogamy is rare, with extra-pair paternity (EPP) occurring in almost 90% of surveyed socially monogamous species. We present the first molecular data on the genetic breeding system of the long-tailed finch, Poephila acuticauda, a grass finch endemic to the tropical northern savannah of Australia. Although the species forms socially monogamous pair bonds during the breeding season, we found that extra-pair males sired 12.8% of 391 offspring, in 25.7% of 101 broods. Our findings provide only the second estimate of extra-pair paternity in the estrildid finch family.


Risk of urinary bladder cancer: a case-control analysis of industry and occupation.
Uncertainty remains about urinary bladder cancer (UBC) risk for many occupations. Here, we investigate the association between occupation, industry and UBC. Lifetime occupational history was collected by in-person interview for 604 newly diagnosed UBC patients and 604 cancer-free controls. Each job title was assigned a two-digit industry code and a three-digit occupation code. Odds ratios (ORs) for UBC associated with ever being employed in an industry or occupation were calculated by unconditional logistic regression adjusting for age, gender and smoking status. We also examined UBC risk by duration of employment (>0 to <10, >or=10 years) in industry or occupation. Significantly increased risk of UBC was observed among waiters and bartenders (OR 2.87; 95% CI 1.05 to 7.72) and occupations related to medicine and health (OR 2.17; 95% CI 1.21 to 3.92), agricultural production, livestock and animal specialties (OR 1.90; 95% CI 1.03 to 3.49), electrical assembly, installation and repair (OR 1.69; 95% CI 1.07 to 2.65), communications (OR 1.74; 95% CI 1.00 to 3.01), and health services (OR 1.58; 95% CI 1.02 to 2.44). For these occupations we also observed a significant excess risk of UBC for long-term work (i.e. >or=10 years), with the exception of waiters and bartenders. Employment for 10 years or more was associated with increased risk of UBC in general farmers (OR 9.58; 95% CI 2.18 to 42.05), agricultural production of crops (OR 3.36; 95% CI 1.10 to 10.27), occupations related to bench working (OR 4.76; 95% CI 1.74 to 13.01), agricultural, fishery, forestry & related (OR 4.58; 95% CI 1.97 to 10.65), transportation equipment (OR 2.68; 95% CI 1.03 to 6.97), and structural work (OR 1.85; 95% CI 1.16 to 2.95). This study provides evidence of increased risk of UBC for occupations that were previously reported as at-risk. Workers in several occupation and industry groups have a significantly higher risk of UBC, particularly when duration of employment is 10 years or more.


Acupuncture Reduces Pain and Autonomic Distress During Injection of Local Anesthetic in Children: A Pragmatic Crossover Investigation.
Stimulation of acupoint LI4 has been shown to result in analgesic effects in patients experiencing acute pain. We aimed to study the effectiveness of LI4 stimulation for pain relief in children receiving an injection of a local anesthetic (LA). Children scheduled for dental treatment using LA received bilateral acupuncture at LI4 using indwelling fixed needles. During the treatment, the parents of the patients stimulated the needles by massage. Two different treatment regimes were compared: a standardized LA injection given 5 minutes after acupuncture, and an LA injection without acupuncture. The order of treatment was randomized, with the 2 treatments performed in a crossover manner on different days. Pain intensity during LA injection, assessed by the patient with the Verbal Rating Scale or Faces Pain Scale (0 to 10), was used as the primary endpoint. Parent-assessed and dentist-assessed pain intensity and agitation, heart rate, and the patients' satisfaction with the therapy were also recorded. Data were obtained from 49 patients (22 female; mean age 10 y). Patients reported less pain when acupuncture was used: mean 2.3 (95% confidence interval, 1.5-3.1) versus 3.9 (95% confidence interval, 3.0-4.7); P<0.001. The patients' heart rate remained low throughout the dental treatment after LI4 stimulation, when compared with treatment without acupuncture (P<0.05). LI4 stimulation was safe and increased satisfaction levels in both the patients and their parents, when compared with LA injection alone (P<0.05). Stimulation of acupoint LI4 reduces pain and autonomic distress in children during LA injection in dental procedures.


Signalling ballet in space and time.
Although we have amassed extensive catalogues of signalling network components, our understanding of the spatiotemporal control of emergent network structures has lagged behind. Dynamic behaviour is starting to be explored throughout the genome, but analysis of spatial behaviours is still confined to individual proteins. The challenge is to reveal how cells integrate temporal and spatial information to determine specific biological functions. Key findings are the discovery of molecular signalling machines such as Ras nanoclusters, spatial activity gradients and flexible network circuitries that involve transcriptional feedback. They reveal design principles of spatiotemporal organization that are crucial for network function and cell fate decisions.


The dilemma of re-licensing DWI offenders: The offenders' point of view.
In many jurisdictions, drivers convicted for the first-time of driving while impaired by alcohol undertake a risk assessment that will determine the severity of sanctions and the remedial measures they must follow as requisites for re-licensing. There is uncertainty inherent in the assessment of risk for recidivism, however, many offenders feel unfairly assessed and discommoded by the decision-making process and its consequences. The objective of this qualitative study was to gain insight into the perspectives of offenders regarding re-licensing decision making and sanctioning. Specifically, in focus groups first-time offenders and recidivists were probed as to whether they favoured erring on the side of road safety in decision making, with its consequent greater risk of false positive assessments, or erring on the side of maintaining driving privileges, with its consequent greater risk of false negative assessments. In general, participants preferred a higher probability of false negative vs. false positive assessments. Most cited the consequences of sanctions and remedial measures as too severe to impose them on potentially low-risk drivers, as the assessment and monitoring protocols' limitations could lead to non-equitable treatment. At the same time, recidivists evoked a greater preference for a higher probability of false positive assessments compared to first-time offenders, as they believed that recidivism was more likely to follow a first conviction than did first-time offenders. This information can be useful for a more comprehensive and societally coherent exercise of DWI prevention policies.


Evidence of concurrent local adaptation and high phenotypic plasticity in a polar microeukaryote.
Here we investigated whether there is evidence of local adaptation in strains of an ancestrally marine dinoflagellate to the lacustrine environment they now inhabit (optimal genotypes) and/or if they have evolved phenotypic plasticity (a range of phenotypes). Eleven strains of Polarella glacialis were isolated and cultured from three different environments: the polar seas, a hyposaline and a hypersaline Antarctic lake. Local adaptation was tested by comparing growth rates of lacustrine and marine strains at their own and reciprocal site conditions. To determine phenotypic plasticity, we measured the reaction norm for salinity. We found evidence of both, limited local adaptation and higher phenotypic plasticity in lacustrine strains when compared with marine ancestors. At extreme high salinities, local lake strains outperformed other strains, and at extreme low salinities, strains from the hyposaline lake outperformed all other strains. The data suggest that lake populations may have evolved higher phenotypic plasticity in the lake habitats compared with the sea, presumably due to the high temporal variability in salinity in the lacustrine systems. Moreover, the interval of salinity tolerance differed between strains from the hyposaline and hypersaline lakes, indicating local adaptation promoted by different salinity.


An in vitro assay to study regulated mRNA stability.
The examination of posttranscriptional regulation of mRNA in mammalian cells is critical to discovering the role that mRNA plays in the initiation and maintenance of cellular processes. The complexity of the system defies a holistic approach and, therefore, we have devised an in vitro mRNA turnover assay that enables us to elucidate the factors involved in mRNA deadenylation and degradation. Our system, using an S100 HeLa extract and in vitro transcribed RNAs, accurately mimics the end products of mRNA turnover, which have been previously described using in vivo studies and, in addition, allows for the detailed study of factors that may play a role in regulated deadenylation and degradation. Another important aspect of our system is the ease with which it can be manipulated. We can provide any synthetic RNA molecule to the assay to test for specific sequence activity. Furthermore, the results are clear and accurately interpretable. We have demonstrated that our in vitro system accurately deadenylates and decays a capped and polyadenylated RNA molecule in a processive manner without nonspecific nuclease activity. Finally, we have demonstrated regulated instability in vitro using the AU-rich elements (AREs) from tumor necrosis factor-alpha (TNF-alpha) and granulocyte macrophage colony stimulating factor (GM-CSF) embedded within the RNA molecule. The presence of the AREs increased the deadenylation and the decay rates seen in vivo. We feel that this system can be expanded and adapted to examine a variety of mRNA regulatory events in mammalian cells.


Usual populations, unusual individuals: insights into the behavior and management of Asian elephants in fragmented landscapes.
A dearth in understanding the behavior of Asian elephants (Elephas maximus) at the scale of populations and individuals has left important management issues, particularly related to human-elephant conflict (HEC), unresolved. Evaluation of differences in behavior and decision-making among individual elephants across groups in response to changing local ecological settings is essential to fill this gap in knowledge and to improve our approaches towards the management and conservation of elephants. We hypothesized certain behavioral decisions that would be made by Asian elephants as reflected in their residence time and movement rates, time-activity budgets, social interactions and group dynamics in response to resource availability and human disturbance in their habitat. This study is based on 200 h of behavioral observations on 60 individually identified elephants and a 184-km(2) grid-based survey of their natural and anthropogenic habitats within and outside the Bannerghatta National Park, southern India during the dry season. At a general population level, the behavioral decisions appeared to be guided by the gender, age and group-type of the elephants. At the individual level, the observed variation could be explained only by the idiosyncratic behaviors of individuals and that of their associating conspecific individuals. Recursive partitioning classification trees for residence time of individual elephants indicated that the primary decisions were taken by individuals, independently of their above-mentioned biological and ecological attributes. Decision-making by Asian elephants thus appears to be determined at two levels, that of the population and, more importantly, the individual. Models based on decision-making by individual elephants have the potential to predict conflict in fragmented landscapes that, in turn, could aid in mitigating HEC. Thus, we must target individuals, in addition to populations, in our efforts to manage and conserve this threatened species, particularly in human-dominated landscapes.


Association Between Primary Care Practitioner Empathy and Risk of Cardiovascular Events and All-Cause Mortality Among Patients With Type 2 Diabetes: A Population-Based Prospective Cohort Study.
To examine the association between primary care practitioner (physician and nurse) empathy and incidence of cardiovascular disease (CVD) events and all-cause mortality among patients with type 2 diabetes. This was a population-based prospective cohort study of 49 general practices in East Anglia (United Kingdom). The study population included 867 individuals with screen-detected type 2 diabetes who were followed up for an average of 10 years until December 31, 2014 in the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care (ADDITION)-Cambridge trial. Twelve months after diagnosis, patients assessed practitioner empathy and their experiences of diabetes care during the preceding year using the consultation and relational empathy (CARE) measure questionnaire. CARE scores were grouped into tertiles. The main outcome measures were first recorded CVD event (a composite of myocardial infarction, revascularization, nontraumatic amputation, stroke, and fatal CVD event) and all-cause mortality, obtained from electronic searches of the general practitioner record, national registries, and hospital records. Hazard ratios (HRs) were estimated using Cox models adjusted for relevant confounders. The ADDITION-Cambridge trial is registered as ISRCTN86769081. Of the 628 participants with a completed CARE score, 120 (19%) experienced a CVD event, and 132 (21%) died during follow up. In the multivariable model, compared with the lowest tertile, higher empathy scores were associated with a lower risk of CVD events (although this did not achieve statistical significance) and a lower risk of all-cause mortality (HRs for the middle and highest tertiles, respectively: 0.49; 95% CI, 0.27-0.88, P = .01 and 0.60; 95% CI, 0.35-1.04, P = .05). Positive patient experiences of practitioner empathy in the year after diagnosis of type 2 diabetes may be associated with beneficial long-term clinical outcomes. Further work is needed to understand which aspects of patient perceptions of empathy might influence health outcomes and how to incorporate this understanding into the education and training of practitioners.


Investigation of Multisequence Magnetic Resonance Imaging for Detection of Recurrent Tumor After Transurethral Resection for Bladder Cancer.
The aim of this study was to evaluate multisequence magnetic resonance imaging (MRI) in detecting local recurrence after transurethral resection for bladder cancer. Thirty-six patients with bladder cancer with previous transurethral resection underwent bladder MRI incorporating T2-weighted imaging, diffusion-weighted imaging, and delayed contrast-enhanced T1-weighted imaging, followed by cystoscopy. Two radiologists (R1 and R2) evaluated examinations for suspicious findings. Forty-seven percent of patients had recurrent tumor at cystoscopy and biopsy. Using multisequence MRI, sensitivity and specificity were 67% and 81% for R1 and 73% and 62% for R2. Both readers missed 1 high-grade pathologic stage T1 recurrent tumor; otherwise, all missed tumors were low-grade pathologic stage Ta lesions. All false positives for R1 and 7 of 9 false positives for R2 were in patients receiving previous bacillus Calmette-Guerin therapy. Furthermore, 40% to 50% of solitary abnormalities and 83% to 100% of multifocal abnormalities were tumor recurrences; 12% to 20% of smooth wall thickening, 50% to 75% of irregular wall thickening, and 88% to 100% of papillary masses were tumor recurrences. Although multisequence MRI exhibited moderate performance for detecting recurrent tumor, nearly all missed tumors were low grade and noninvasive.


Evolving Gaussian Mixture Models with Splitting and Merging Mutation Operators.
This paper describes the evolutionary split and merge for expectation maximization (ESM-EM) algorithm and eight of its variants, which are based on the use of split and merge operations to evolve Gaussian mixture models. Asymptotic time complexity analysis shows that the proposed algorithms are competitive with the state-of-the-art genetic-based expectation maximization (GA-EM) algorithm. Experiments performed in 35 data sets showed that ESM-EM can be computationally more efficient than the widely used multiple runs of EM (for different numbers of components and initializations). Moreover, a variant of ESM-EM free from critical parameters was shown to be able to provide competitive results with GA-EM, even when GA-EM parameters were fine-tuned a priori.


Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment.
The effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight are not well characterized. Also unknown is whether different agents have differential effects. To examine these questions, we assessed weight changes in patients randomly assigned to long-term treatment with fluoxetine, sertraline, or paroxetine. Patients (N = 284) with major depressive disorder (DSM-IV) were randomly assigned to double-blind treatment with fluoxetine (N = 92), sertraline, (N = 96), or paroxetine (N = 96) for a total of 26 to 32 weeks. The mean percent change in weight was compared for each group, as was the number of patients who had > or = 7% weight increase from baseline. Patients (fluoxetine, N = 44; sertraline, N = 48; paroxetine, N = 47) who completed the trial were included in these analyses. Paroxetine-treated patients experienced a significant weight increase, fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest but nonsignificant weight increase. The number of patients whose weight increased > 7% from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients. Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used.


Advances in the management of spinal cord injury.
Historically, clinical outcomes following spinal cord injury have been dismal. Over the past 20 years, the survival rate and long-term outcome of patients with spinal cord injury have improved with advances in both medical and surgical treatment. However, the efficacy and timing of these adjuvant treatments remain controversial. There has been a tremendous increase in the number of basic science and clinical studies on spinal cord injury. Current areas of investigation include early acute management, including early surgical intervention, as well as new pharmacotherapy and cellular transplantation strategies. It is unlikely that a single approach can uniformly address all of the issues associated with spinal cord injury. Thus, a multidisciplinary approach will be needed.


Nicotine, carbon monoxide, and carcinogen exposure after a single use of a water pipe.
Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world, including the United States, where it is especially popular among young people. Many perceive water pipe smoking to be less hazardous than cigarette smoking. We studied systemic absorption of nicotine, carbon monoxide, and carcinogens from one water pipe smoking session. Sixteen subjects smoked a water pipe on a clinical research ward. Expired carbon monoxide and carboxyhemoglobin were measured, plasma samples were analyzed for nicotine concentrations, and urine samples were analyzed for the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and polycyclic aromatic hydrocarbon (PAH) metabolite biomarker concentrations. We found substantial increases in plasma nicotine concentrations, comparable to cigarette smoking, and increases in carbon monoxide levels that are much higher than those typically observed from cigarette smoking, as previously published. Urinary excretion of NNAL and PAH biomarkers increased significantly following water pipe smoking. Absorption of nicotine in amounts comparable to cigarette smoking indicates a potential for addiction, and absorption of significant amounts of carcinogens raise concerns of cancer risk in people who smoke tobacco products in water pipes. Our data contribute to an understanding of the health impact of water pipe use.


Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications.
Vitamin D deficiency is common in the elderly, especially in the housebound and in geriatric patients. The establishment of strict diagnostic criteria is hampered by differences in assay methods for 25-hydroxyvitamin D. The synthesis of vitamin D3 in the skin under influence of UV light decreases with aging due to insufficient sunlight exposure, and a decreased functional capacity of the skin. The diet contains a minor part of the vitamin D requirement. Vitamin D deficiency in the elderly is less common in the United States than elsewhere due to the fortification of milk and use of supplements. Deficiency in vitamin D causes secondary hyperparathyroidism, high bone turnover, bone loss, mineralization defects, and hip and other fractures. Less certain consequences include myopathy and falls. A diet low in calcium may cause an increased turnover of vitamin D metabolites and thereby aggravate vitamin D deficiency. Prevention is feasible by UV light exposure, food fortification, and supplements. Vitamin D3 supplementation causes a decrease of the serum PTH concentration, a decrease of bone turnover, and an increase of bone mineral density. Vitamin D3 and calcium may decrease the incidence of hip and other peripheral fractures in nursing home residents. Vitamin D3 is recommended in housebound elderly, and it may be cost-effective in hip fracture prevention in selected risk groups.


Genomic dynamics of species and mobile genetic elements in a prolonged blaIMP-4-associated carbapenemase outbreak in an Australian hospital.
Hospital outbreaks of carbapenemase-producing organisms, such as blaIMP-4-containing organisms, are an increasing threat to patient safety. To investigate the genomic dynamics of a 10 year (2006-15) outbreak of blaIMP-4-containing organisms in a burns unit in a hospital in Sydney, Australia. All carbapenem-non-susceptible or MDR clinical isolates (2006-15) and a random selection of equivalent or ESBL-producing environmental isolates (2012-15) were sequenced [short-read (Illumina), long-read (Oxford Nanopore Technology)]. Sequence data were used to assess genetic relatedness of isolates (Mash; mapping and recombination-adjusted phylogenies), perform in silico typing (MLST, resistance genes and plasmid replicons) and reconstruct a subset of blaIMP plasmids for comparative plasmid genomics. A total of 46/58 clinical and 67/96 environmental isolates contained blaIMP-4. All blaIMP-4-positive organisms contained five or more other resistance genes. Enterobacter cloacae was the predominant organism, with 12 other species mainly found in either the environment or patients, some persisting despite several cleaning methods. On phylogenetic analysis there were three genetic clusters of E. cloacae containing both clinical and environmental isolates, and an additional four clusters restricted to either reservoir. blaIMP-4 was mostly found as part of a cassette array (blaIMP-4-qacG2-aacA4-catB3) in a class 1 integron within a previously described IncM2 plasmid (pEl1573), with almost complete conservation of this cassette across the species over the 10 years. Several other plasmids were also implicated, including an IncF plasmid backbone not previously widely described in association with blaIMP-4. Genetic backgrounds disseminating blaIMP-4 can persist, diversify and evolve amongst both human and environmental reservoirs during a prolonged outbreak despite intensive prevention efforts.


Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.
To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.


Suppression of intensity noise of a laser-diode-pumped single-frequency Nd:YVO4 laser by optoelectronic control.
The intensity-noise reduction of a laser-diode-pumped single-frequency ring Nd:YVO4 laser when different optoelectronic control systems are used is theoretically and experimentally investigated. It has been demonstrated that combining two techniques, optoelectronic feedback control of the drive current of the pump laser diode and feed-forward control of the output laser beam, is a good way to significantly suppress the intensity noise of a laser at low frequency.


Decussation patterns of the platysma in Koreans.
The importance of the platysma muscle in plastic surgery is well known. During surgery, we have observed that the platysmal fibres do not merely decussate and interlace from each side but that sometimes one side of the muscle overlaps and covers the other side. The aim of this study was to clarify the precise anatomical variations in the decussation and overlapping patterns of the platysma muscle in 70 Korean cadavers. We defined three groups (types I--III) and four patterns (types A--D) according to the length of decussation and the pattern of overlapping, respectively. In 60 specimens (85.7%) we observed decussation and in 10 (14.3%) we did not. In type I there was 0--20 mm of decussating fibres below the mandibular border (43% of specimens). In type II, the decussation of fibres extended over more than 20 mm (43% of specimens). Type III had no decussation (14% of specimens). The proportions of type A (interlacing pattern), type B (right dominant), type C (left dominant) and type D (no decussation) were 41%, 29%, 16% and 14%, respectively. In 45% of the specimens, one side of the platysma covered and overlapped the other side. This is relevant to the removal of the subplatysmal fat in corset platysmaplasty, submental Z-plasty and vertical myectomy of the platysma muscle.


Isomerization mechanisms of stereolabile tris- and bis-bidentate octahedral cobalt(II) complexes: X-ray structure and variable temperature and pressure NMR kinetic investigations.
The isomerization dynamics of five labile octahedral Co(II) compounds have been investigated by variable temperature and pressure (1)H and (19)F NMR spectroscopy in dichloromethane solution. The X-ray crystal structure of the two tris-chelates, [Co(HFA)(2)bpic] (1) and [Co(TTFA)(2)bpy] (2), show a distorted octahedral arrangement of the 4 oxygen and 2 nitrogen donor atoms, with bidentate ligand bite angles smaller than 90 degrees. On the other hand, in the three bis-chelates, trans(N)-[Co(HFA)(2)(CH(3)py)(2)](3), cis(N)-cis(CF(3))-trans(S)-[Co(TTFA)(2)(CH(3)py)(2)](4), and trans(N)-trans(CF(3))-[Co(TTFA)(2)(CF(3)py)(2)](5), the replacement of the bidentate nitrogen donor ligands by two monodentate Rpy ligands leads to relaxed structures with almost regular octahedral arrangements of the donor atoms (HFA = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionato anion; TTFA = 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedionato anion; bpy = 2,2'-bipyridine; bpic = 4,4'-dimethyl-2,2'-bipyridine). In solution the five complexes are stereolabile and all possible isomers are formed: from one for 1 up to five for 4 and 5. All cis-N isomers form pairs of enantiomers, whereas the trans-N isomers are achiral. A solid state structure/isomerization mechanism/rate correlation has been established for the isomerization dynamics of these Co(II) tris- and bis-chelates. The two tris-chelate complexes 1 and 2, with a distorted octahedral solid state structure, show one and three isomers in solution and isomerize/tautomerize very rapidly according to Bailar twist mechanisms. The three bis-chelate complexes 3, 4, and 5, with a close to octahedral symmetry in the solid state, show two, five, and five isomers, respectively. They isomerize/tautomerize 3 orders of magnitude slower as the tris-chelates, by an intramolecular dissociative mechanism involving a ring-opening of an arm of a bidentate ligand to form a TBP intermediate with a dangling bidentate ligand. The results of this first systematic investigation of the isomerization mechanisms of highly labile Co(II) complexes are supported by the NMR observed exchange paths (up to five for complexes for 4 and 5), the variable temperature (185 to 312 K) and pressure (up to 200 MPa) activation parameters, and a detailed analysis of the solid state structures.


Wide tunability of magnetoplasmonic crystals due to excitation of multiple waveguide and plasmon modes.
Magnetoplasmonic crystals (MPC) composed of a 1D gold grating on top of a magnetic garnet layer made by a combined ion-beam etching technique are studied. We demonstrate that this method allows to make high-quality MPC. It is shown that MPC with a 30-40 nm thick perforated gold layer provides an effective excitation of two surface plasmon-polariton modes and several numbers of waveguide modes in the garnet layer. An enhancement of the transversal magneto-optical effect up to the value of 10(-2) is observed for all types of resonant modes, that propagate in the magnetic layer, due to magnetic-field control over the mode excitation which is promising for future photonic devices.


Relationship between local atrial fibrillation interval and refractory period in the isolated canine atrium.
Atrial refractory periods and their spatial distribution are important determinants of atrial reentrant arrhythmias. The objective of this study was to demonstrate a correlation between the local atrial fibrillation interval (AFI) and local effective refractory period (ERP). To measure the local ERP and local AFI under stable conditions without hemodynamic, autonomic, or reflex influences, isolated perfused canine whole atria were used (n = 8). The isolated atria were mounted on two endocardial electrodes. Bipolar electrograms were simultaneously recorded from 253 endocardial sites, and 16 to 20 randomly distributed electrodes were used to measure the local ERP by the extrastimulus technique. In all studies, several episodes of AF were induced by a single extrastimulus. The ERP and minimum AFI converged with increasing duration of AF. The convergence was more rapid if the total duration of AF analyzed came from multiple episodes of AF. The correlation coefficient between the local ERP and minimum local AFI was .92 (n = 119, P < .001). The minimum AFI was used to construct AFI distribution maps at all 253 sites. Activation block during premature stimulation correlated with regions of long AFI. The minimum local AFI measured from at least 10 seconds of AF approximates the local ERP. Construction of a minimum local AFI map during AF can be used to predict the distribution of refractoriness and can be used to predict sites of functional block. Contrary to studies done in intact animals and patients, the AFI were longer than the ERPs, suggesting that reflex changes may shorten ERP in the intact heart.


Cultural and Personality Predictors of Facebook Intrusion: A Cross-Cultural Study.
The increase in the number of users of social networking sites (SNS) has inspired intense efforts to determine intercultural differences between them. The main aim of the study was to investigate the cultural and personal predictors of Facebook intrusion. A total of 2628 Facebook users from eight countries took part in the study. The Facebook Intrusion Questionnaire, the Ten-Item Personality Inventory, and the Singelis Scale were used. We found that two variables related to Country were significantly related to Facebook intrusion: uniqueness (negatively) and low context (positively); of the personality variables, conscientiousness, and emotional stability were negatively related to the dependent variable of Facebook intrusion across different countries, which may indicate the universal pattern of Facebook intrusion. The results of the study will contribute to the international debate on the phenomenon of SNS.


Molecular and isotopic biogeochemistry on recently-formed soils on King George Island (Maritime Antarctica) after glacier retreat upon warming climate.
Maritime Antarctica is a climate-sensitive region that has experienced a continuous increase of temperature over the last 50 years. This phenomenon accelerates glacier retreat and promotes the exposure of ice-covered surfaces, triggering physico-chemical alteration of the ground and subsequent soil formation. Here, we studied the biogeochemical composition and evolution extent of soil on three recently exposed peninsulas (Fildes, Barton and Potter) on Southwest (SW) King George Island (KGI). Nine soil samples were analyzed for their lipid biomarkers, stable isotope composition, bulk geochemistry and mineralogy. Their biomarkers profiles were compared to those of local fresh biomass of microbial mats (n = 3) and vegetation (1 moss, 1 grass, and 3 lichens) to assess their contribution to the soil organic matter (SOM). The molecular and isotopic distribution of lipids in the soil samples revealed contributions to the SOM dominated by biogenic sources, mostly vegetal (i.e. odd HMW n-alkanes distributions and generally depleted δ13C ratios). Microbial sources were also present to a lesser extent (i.e. even LMW n-alkanes and n-alkanoic acids, heptadecane, 1-alkenes, 9-octadecenoic acid, or iso/anteiso 15: 0 and 17:0 alkanoic acids). Additional contribution from petrogenic sources (bedrock erosion-derived hydrocarbons) was also considered although found to be minor. Results from mineralogy (relative abundance of plagioclases and virtual absence of clay minerals) and bulk geochemistry (low chemical weathering indexes) suggested little chemical alteration of the original geology. This together with the low content of total nitrogen and organic carbon, as well as moderate microbial activity in the soils, confirmed little edaphological development on the recently-exposed KGI surfaces. This study provides molecular and isotopic fingerprints of SOM composition in young Antarctic soils, and contributes to the understanding of soil formation and biogeochemistry in this unexplored region which is currently being affected by thermal destabilization.


An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation.
Because of suboptimal therapeutic strategies, restoration of sinus rhythm in symptomatic atrial fibrillation (AF) often requires in-hospital delivery of high-voltage shocks, thereby precluding ambulatory AF termination. Continuous, rapid restoration of sinus rhythm is desired given the recurring and progressive nature of AF. Here, we present an automated hybrid bioelectronic system for shock-free termination of AF that enables the heart to act as an electric current generator for autogenous restoration of sinus rhythm. We show that local, right atrial delivery of adenoassociated virus vectors encoding a light-gated depolarizing ion channel results in efficient and spatially confined transgene expression. Activation of an implanted intrathoracic light-emitting diode device allows for termination of AF by illuminating part of the atria. Combining this newly obtained antiarrhythmic effector function of the heart with the arrhythmia detector function of a machine-based cardiac rhythm monitor in the closed chest of adult rats allowed automated and rapid arrhythmia detection and termination in a safe, effective, repetitive, yet shock-free manner. These findings hold translational potential for the development of shock-free antiarrhythmic device therapy for ambulatory treatment of AF.


Atomistic Insight into Tetraalkylphosphonium-Bis(oxalato)borate Ionic Liquid/Water Mixtures. I. Local Microscopic Structure.
Atomistic simulations have been performed to investigate the microscopic structural organization of aqueous solutions of trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL). The evolution of the microscopic liquid structure and the local ionic organization of IL/water mixtures as a function of the water concentration is visualized and systematically analyzed via radial and spatial distribution functions, coordination numbers, hydrogen bond network, and water clustering analysis. The microscopic liquid structure in neat IL is characterized by a connected apolar network composed of the alkyl chains of [P6,6,6,14] cations and isolated polar domains consisting of the central segments of [P6,6,6,14] cations and [BOB] anions, and the corresponding local ionic environment is described by direct contact ion pairs. In IL/water mixtures with lower water mole fractions, the added water molecules are dispersed and embedded in cavities between neighboring ionic species and the local ionic structure is characterized by solvent-shared ion pairs through cation-water-anion triple complexes. With a gradual increase in the water concentration in IL/water mixtures, the added water molecules tend to aggregate and form small clusters, intermediate chain-like structures, large aggregates, and eventually a water network in water concentrated simulation systems. A further progressive dilution of IL/water mixtures leads to the formation of self-organized micelle-like aggregates characterized by a hydrophobic core and hydrophilic shell consisting of the central polar segments in [P6,6,6,14] cations and [BOB] anions in a highly branched water network. The striking structural evolution of the [P6,6,6,14][BOB] IL/water mixtures is rationalized by the competition between favorable hydrogen bonded interactions and strong electrostatic interactions between the polar segments in ionic species and the dispersion interactions between the hydrophobic alkyl chains in [P6,6,6,14] cations.


Transmission of SARS-CoV-2 Associated with Cruise Ship Travel: A Systematic Review.
Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose−response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21−39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed.


Neural circuitry coordinating male copulation.
Copulation is the goal of the courtship process, crucial to reproductive success and evolutionary fitness. Identifying the circuitry underlying copulation is a necessary step towards understanding universal principles of circuit operation, and how circuit elements are recruited into the production of ordered action sequences. Here, we identify key sex-specific neurons that mediate copulation in Drosophila, and define a sexually dimorphic motor circuit in the male abdominal ganglion that mediates the action sequence of initiating and terminating copulation. This sexually dimorphic circuit composed of three neuronal classes - motor neurons, interneurons and mechanosensory neurons - controls the mechanics of copulation. By correlating the connectivity, function and activity of these neurons we have determined the logic for how this circuitry is coordinated to generate this male-specific behavior, and sets the stage for a circuit-level dissection of active sensing and modulation of copulatory behavior.


The relationship between job satisfaction and health: a meta-analysis.
A vast number of published studies have suggested a link between job satisfaction levels and health. The sizes of the relationships reported vary widely. Narrative overviews of this relationship have been published, but no systematic meta-analysis review has been conducted. A systematic review and meta-analysis of 485 studies with a combined sample size of 267 995 individuals was conducted, evaluating the research evidence linking self-report measures of job satisfaction to measures of physical and mental wellbeing. The overall correlation combined across all health measures was r = 0.312 (0.370 after Schmidt-Hunter adjustment). Job satisfaction was most strongly associated with mental/psychological problems; strongest relationships were found for burnout (corrected r = 0.478), self-esteem(r = 0.429), depression (r = 0.428), and anxiety(r = 0.420). The correlation with subjective physical illness was more modest (r = 0.287). Correlations in excess of 0.3 are rare in this context. The relationships found suggest that job satisfaction level is an important factor influencing the health of workers. Organisations should include the development of stress management policies to identify and eradicate work practices that cause most job dissatisfaction as part of any exercise aimed at improving employee health. Occupational health clinicians should consider counselling employees diagnosed as having psychological problems to critically evaluate their work-and help them to explore ways of gaining greater satisfaction from this important aspect of their life.


Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression.
Rapid accumulation and availability of gene expression datasets in public repositories have enabled large-scale meta-analyses of combined data. The richness of cross-experiment data has provided new biological insights, including identification of new cancer genes. In this study, we compiled a human gene expression dataset from ∼40,000 publicly available Affymetrix HG-U133Plus2 arrays. After strict quality control and data normalisation the data was quantified in an expression matrix of ∼20,000 genes and ∼28,000 samples. To enable different ways of sample grouping, existing annotations where subjected to systematic ontology assisted categorisation and manual curation. Groups like normal tissues, neoplasmic tissues, cell lines, homoeotic cells and incompletely differentiated cells were created. Unsupervised analysis of the data confirmed global structure of expression consistent with earlier analysis but with more details revealed due to increased resolution. A suitable mixed-effects linear model was used to further investigate gene expression in solid tissue tumours, and to compare these with the respective healthy solid tissues. The analysis identified 1,285 genes with systematic expression change in cancer. The list is significantly enriched with known cancer genes from large, public, peer-reviewed databases, whereas the remaining ones are proposed as new cancer gene candidates. The compiled dataset is publicly available in the ArrayExpress Archive. It contains the most diverse collection of biological samples, making it the largest systematically annotated gene expression dataset of its kind in the public domain.


Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p'-dde levels in a population-based sample.
Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p,p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied. Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472ng/g lipid, while the corresponding level for those being homozygote for the T allele was 192ng/g lipid (p=1.5×10-31). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19:41520351; p=2.2×10-8). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p=6.2×10-9) located 7kb downstream the CYP2B6 gene (cg27089200, position chr19:41531976). This CpG-site was also related to the lead SNP (p=3.8×10-35), but mediated only 4% of the effect of the lead SNP on p,p'-DDE levels. Circulating levels of p,p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p,p'-DDE levels.


Role of Solvent Water in the Temperature-Induced Self-Assembly of a Triblock Copolymer.
Water-soluble triblock copolymers have received much attention in industrial applications and scientific fields. We here show that femtosecond mid-IR pump-probe spectroscopy is useful to study the role of water in the temperature-induced self-assembly of triblock copolymers. Our experimental results suggest two distinct subpopulations of water molecules: those that interact with other water molecules and those involved in the hydration of a triblock copolymer surface. We find that the vibrational dynamics of bulk-like water is not affected by either micellation or gelation of triblock copolymers. The increased population of water interacting with ether oxygen atoms of the copolymer during the unimer to micelle phase transition is important evidence for the entropic role of water in temperature-induced micelle formation at a low copolymer concentration. In contrast, at the critical gelation temperature and beyond, the population of surface-associated water molecules interacting with ether oxygen atoms decreases, which indicates important enthalpic control by water. The present study on the roles of water in the two different phase transitions of triblock copolymers sheds new light on the underlying mechanisms of temperature-induced self-aggregation behaviors of amphiphiles that are ubiquitous in nature.


The military and the transition to adulthood.
Ryan Kelty, Meredith Kleykamp, and David Segal examine the effect of military service on the transition to adulthood. They highlight changes since World War II in the role of the military in the lives of young adults, focusing especially on how the move from a conscription to an all-volunteer military has changed the way military service affects youths' approach to adult responsibilities. The authors note that today's all-volunteer military is both career-oriented and family-oriented, and they show how the material and social support the military provides to young servicemen and women promotes responsible membership in family relationships and the wider community. As a result, they argue, the transition to adulthood, including economic independence from parents, is more stable and orderly for military personnel than for their civilian peers. At the same time, they stress that serving in the military in a time of war holds dangers for young adults. The authors examine four broad areas of military service, focusing in each on how men and women in uniform today make the transition to adulthood. They begin by looking at the social characteristics of those who serve, especially at differences in access to the military and its benefits by socio-demographic characteristics, such as age, gender, race and ethnicity, social class, and sexual orientation. Military service also has important effects on family formation, including the timing of marriage and parenthood, family structure, and the influence of military culture on families. Family formation among servicemen and women, the authors observe, is earlier and more stable than among civilians of the same age. The authors then consider the educational and employment consequences of service. Finally, they scrutinize the dangers of military service during times of war and examine the physical and psychological effects of wartime military service. They also note the sexual trauma endured both by male and female military personnel and the physical and symbolic violence women can experience in a male-dominated institution. Kelty, Kleykamp, and Segal conclude by seeking policy lessons from the military's success in facilitating the transition to adulthood for young men and women in uniform.


Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.
Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041). Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.


MR evaluation of synovial injury in shoulder trauma.
The purpose of this study was to determine magnetic resonance imaging (MRI) findings relevant to synovial injury of the shoulder in patients with and without acute shoulder trauma. Three hundred and nine consecutive shoulder MRI studies (185-male, 124-female, 50 ± 15 years old) were retrospectively evaluated for findings suggestive of synovial injury including rupture and/or diverticulum of the joint capsule, bursa, and biceps tendon sheath (BTS), ganglion/synovial cyst, geyser phenomenon, and sequel of previous shoulder dislocation (Hill-Sachs deformity). Patients with one or more of these findings were included in the MR-positive group, whereas the remaining subjects were used as MR negatives. Based on their medical records, patients were also divided into trauma and non-trauma groups, and statistical analysis was performed to evaluate the association between the aforementioned MRI findings and history of shoulder trauma. Fifty-six patients were included in the MR-positive group and 253 in the MR-negative group. In MR-positive group, the incidence of capsular rupture (CR) and subacromial/subdeltoid (SASD) bursal rupture was higher in trauma patients, whereas the incidence of BTS diverticulum and ganglion cyst was higher in subjects without trauma. Significant association was found between the history of acute trauma and CR, SASD bursal rupture, BTS rupture, and Hill-Sachs deformity. In shoulder MR examination, presence of CR and/or SASD bursal rupture is strongly suggestive of acute shoulder trauma. In addition, BTS rupture and Hill-Sachs deformity are more prevalent in patients with acute shoulder trauma. The presence of these features should alert MRI readers to assess for additional trauma-related internal derangements, if a respective history has not been provided.


The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome.
The volitional impairments of alien limb and apraxia are a defining feature of the corticobasal syndrome, but a limited understanding of their neurocognitive aetiology has hampered progress towards effective treatments. Here we combined several key methods to investigate the mechanism of impairments in voluntary action in corticobasal syndrome. We used a quantitative measure of awareness of action that is based on well-defined processes of motor control; structural and functional anatomical information; and evaluation against the clinical volitional disorders of corticobasal syndrome. In patients and healthy adults we measured 'intentional binding', the perceived temporal attraction between voluntary actions and their sensory effects. Patients showed increased binding of the perceived time of actions towards their effects. This increase correlated with the severity of alien limb and apraxia, which we suggest share a core deficit in motor control processes, through reduced precision in voluntary action signals. Structural neuroimaging analyses showed the behavioural variability in patients was related to changes in grey matter volume in pre-supplementary motor area, and changes in its underlying white matter tracts to prefrontal cortex. Moreover, changes in functional connectivity at rest between the pre-supplementary motor area and prefrontal cortex were proportional to changes in binding. These behavioural, structural and functional results converge to reveal the frontal network for altered awareness and control of voluntary action in corticobasal syndrome, and provide candidate markers to evaluate new therapies.


High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential.
Current musculoskeletal imaging techniques usually target the macro-morphology of articular cartilage or use histological analysis. These techniques are able to reveal advanced osteoarthritic changes in articular cartilage but fail to give detailed information to distinguish early osteoarthritis from healthy cartilage, and this necessitates high-resolution imaging techniques measuring cells and the extracellular matrix within the multilayer structure of articular cartilage. This review provides a comprehensive exploration of the cellular components and extracellular matrix of articular cartilage as well as high-resolution imaging techniques, including magnetic resonance image, electron microscopy, confocal laser scanning microscopy, second harmonic generation microscopy, and laser scanning confocal arthroscopy, in the measurement of multilayer ultra-structures of articular cartilage. This review also provides an overview for micro-structural analysis of the main components of normal or osteoarthritic cartilage and discusses the potential and challenges associated with developing non-invasive high-resolution imaging techniques for both research and clinical diagnosis of early to late osteoarthritis.


Assessing prenatal depression in the rural developing world: a comparison of two screening measures.
Significant levels of prenatal depression are reported from the Indian subcontinent (25–45%). A wide variety of measures have been used to screen for prenatal depression in western research. However, little evidence exists on the use of such measures in the context of the developing world. The objective of this study was to assess the validity of the Edinburgh Postnatal Depression Scale (EPDS) and the Kessler 10 Scale of Psychological Distress (K10) as screening measures for prenatal depression in rural South India. One hundred ninety-four women in their third trimester of pregnancy were assessed at a rural prenatal clinic in Karnataka, South India, using the EPDS, the K10 (scored 0–40) and a structured diagnostic psychiatric interview to establish a DSM-IV diagnosis of depression. Depressed women scored significantly higher on the EPDS and K-10 than controls. A receiver-operating characteristic analyses showed both scales to be good screening instruments for prenatal depression in rural South India at a cut-off of ≥13 on the EPDS (sensitivity = 100%, specificity = 84.90%, and area under the curve = 0.95) and ≥6 on the K10 (sensitivity = 100%, specificity = 81.30%, and area under the curve = 0.95). The EPDS and K10 have thus been shown to have equally good sensitivity and specificity in rural settings in the developing world at a cut-off score of ≥13 and ≥6, respectively. This study demonstrates the validity of the EPDS and K10 in screening pregnant women for depression during their prenatal check-ups.


Risk factors for sexually transmitted diseases among women attending family planning clinics in Dar-es-Salaam, Tanzania.
Identification of risk factors for sexually transmitted diseases (STDs) assists in development of treatment algorithms, which are potentially important components of STD control when microbiologic facilities are limited. A cross-sectional study was performed to assess STD and HIV risk factors of 2285 women attending three family planning clinics in Dar-es-Salaam, Tanzania during 1991-92. Women were interviewed and examined for signs of STDs. Specimens were taken for laboratory diagnosis of HIV, other sexually transmitted organisms, and Candida albicans. The prevalence of gonorrhoea was found to be 4.2%, prevalence of trichomoniasis was 14.3%, and positive syphilis serology was found in 2.5% of women. Unmarried women were at increased risk of trichomoniasis (age-adjusted OR = 1.48 95% CI [1.12, 1.95]), gonorrhoea (age-adjusted OR = 1.81 95% CI [1.14, 2.86]) and syphilis (age-adjusted OR 1.5 [0.84, 2.68]). An increasing number of sexual partners in the past five years was associated with an increased risk of all STDs. Current use of the oral contraceptive pill was positively associated with gonorrhoea, multivariate OR = 1.75 95% CI [1.05, 2.93]. The prevalence of candidiasis was 11.5% and was not associated with any of the demographic or behavioural risk factors examined. Clinical diagnostic algorithms for STDs in this study population had relatively low sensitivity and low positive predictive value. Being unmarried and having a higher number of sexual partners were consistently associated with each STD, while the associations for other risk factors varied between STDs, emphasising the complexity of STD distribution. Further development of diagnostic algorithms and other methods for screening women for STDs are needed to reduce the impact of STDs and HIV in developing countries.


Identifying older patients with acute myeloid leukemia who may be candidates for reduced-intensity hematopoietic cell transplantation.
Recent studies show that with reduced-intensity and nonmyeloablative conditioning regimens, allogeneic hematopoietic cell transplantation can now be performed with relative safety in patients with acute myeloid leukemia up to 75 years of age, and therefore chronologic age itself should no longer be considered a contraindication for this procedure. Best results are generally seen in patients undergoing transplant during first remission. Results appear superior to what might be expected with conventional chemotherapy but prospective randomized trials have not been completed. If a decision is made to delay transplant until first relapse, a careful monitoring plan should be established.