Bioenergy potential of the United States constrained by satellite observations of existing productivity.
United States (U.S.) energy policy includes an expectation that bioenergy will be a substantial future energy source. In particular, the Energy Independence and Security Act of 2007 (EISA) aims to increase annual U.S. biofuel (secondary bioenergy) production by more than 3-fold, from 40 to 136 billion liters ethanol, which implies an even larger increase in biomass demand (primary energy), from roughly 2.9 to 7.4 EJ yr(-1). However, our understanding of many of the factors used to establish such energy targets is far from complete, introducing significgant uncertainty into the feasibility of current estimates of bioenergy potential. Here, we utilized satellite-derived net primary productivity (NPP) data-measured for every 1 km(2) of the 7.2 million km(2) of vegetated land in the conterminous U.S.-to estimate primary bioenergy potential (PBP). Our results indicate that PBP of the conterminous U.S. ranges from roughly 5.9 to 22.2 EJ yr(-1), depending on land use. The low end of this range represents the potential when harvesting residues only, while the high end would require an annual biomass harvest over an area more than three times current U.S. agricultural extent. While EISA energy targets are theoretically achievable, we show that meeting these targets utilizing current technology would require either an 80% displacement of current crop harvest or the conversion of 60% of rangeland productivity. Accordingly, realistically constrained estimates of bioenergy potential are critical for effective incorporation of bioenergy into the national energy portfolio.


Soliton self-frequency shift decelerated by self-steepening.
Self-steepening of ultrashort light pulses is shown to reduce the soliton self-frequency shift (SSFS) induced by the Raman effect in an optical fiber. We derive an analytical expression for the SSFS that conserves the number of photons and allows the SSFS to be calculated for arbitrary frequency profiles of fiber dispersion and Raman gain without a numerical solution of the pulse evolution equation. The accuracy of this analytical approach to SSFS calculation is tested by numerical simulations based on the generalized nonlinear Schrödinger equation.


Linkage mapping and physical localization of the major histocompatibility complex region of the marsupial Monodelphis domestica.
We used genetic linkage mapping and fluorescence in situ hybridization (FISH) to conduct the first analysis of genic organization and chromosome localization of the major histocompatibility complex (MHC) of a marsupial, the gray, short-tailed opossum Monodelphis domestica. Family based linkage analyses of two M. domestica MHC Class I genes (UA1, UG) and three MHC Class II genes (DAB, DMA, and DMB) revealed that these genes were tightly linked and positioned in the central region of linkage group 3 (LG3). This cluster of MHC genes was physically mapped to the centromeric region of chromosome 2q by FISH using a BAC clone containing the UA1 gene. An interesting finding from the linkage analyses is that sex-specific recombination rates were virtually identical within the MHC region. This stands in stark contrast to the genome-wide situation, wherein males exhibit approximately twice as much recombination as females, and could have evolutionary implications for maintaining equality between males and females in the ability to generate haplotype diversity in this region. These analyses also showed that three non-MHC genes that flank the MHC region on human chromosome 6, myelin oligodendrocyte glycoprotein (MOG), bone morphogenetic protein 6 (BMP6), and prolactin (PRL), are split among two separate linkage groups (chromosomes) in M. domestica. Comparative analysis with eight other vertebrate species suggests strong conservation of the BMP6-PRL synteny among birds and mammals, although the BMP6-PRL-MHC-ME1 synteny is not conserved.


Inter-trial effects in priming of pop-out: Comparison of computational updating models.
In visual search tasks, repeating features or the position of the target results in faster response times. Such inter-trial 'priming' effects occur not just for repetitions from the immediately preceding trial but also from trials further back. A paradigm known to produce particularly long-lasting inter-trial effects-of the target-defining feature, target position, and response (feature)-is the 'priming of pop-out' (PoP) paradigm, which typically uses sparse search displays and random swapping across trials of target- and distractor-defining features. However, the mechanisms underlying these inter-trial effects are still not well understood. To address this, we applied a modeling framework combining an evidence accumulation (EA) model with different computational updating rules of the model parameters (i.e., the drift rate and starting point of EA) for different aspects of stimulus history, to data from a (previously published) PoP study that had revealed significant inter-trial effects from several trials back for repetitions of the target color, the target position, and (response-critical) target feature. By performing a systematic model comparison, we aimed to determine which EA model parameter and which updating rule for that parameter best accounts for each inter-trial effect and the associated n-back temporal profile. We found that, in general, our modeling framework could accurately predict the n-back temporal profiles. Further, target color- and position-based inter-trial effects were best understood as arising from redistribution of a limited-capacity weight resource which determines the EA rate. In contrast, response-based inter-trial effects were best explained by a bias of the starting point towards the response associated with a previous target; this bias appeared largely tied to the position of the target. These findings elucidate how our cognitive system continually tracks, and updates an internal predictive model of, a number of separable stimulus and response parameters in order to optimize task performance.


A systematic review of measures of HIV/AIDS stigma in paediatric HIV-infected and HIV-affected populations.
HIV-related stigma impacts the quality of life and care management of HIV-infected and HIV-affected individuals, but how we measure stigma and its impact on children and adolescents has less often been described. We conducted a systematic review of studies that measured HIV-related stigma with a quantitative tool in paediatric HIV-infected and HIV-affected populations. Varying measures have been used to assess stigma in paediatric populations, with most studies utilizing the full or variant form of the HIV Stigma Scale that has been validated in adult populations and utilized with paediatric populations in Africa, Asia and the United States. Other common measures included the Perceived Public Stigma Against Children Affected by HIV, primarily utilized and validated in China. Few studies implored item validation techniques with the population of interest, although scales were used in a different cultural context from the origin of the scale. Many stigma measures have been used to assess HIV stigma in paediatric populations, globally, but few have implored methods for cultural adaptation and content validity.


Maternal super-obesity.
Pregnant women with a body-mass-index (BMI) above 50 are referred to as "super-obese". For these women adverse pregnancy outcome and a higher risk of fetal congenital defects are major issues. This report focuses on the ratio development of super-obesity in pregnant women, as well as on prenatal ultrasound and pregnancy outcome in the super-obese gravida. We reviewed data of all women with a BMI above 30 who delivered at our unit in a 15-year period between January 2000 and December 2014. Data of obese but not super-obese mothers were evaluated in comparison. Final evaluation comprised 69/20,711 pregnancies of super-obese mothers. Forty out of 69 women suffered from a preexisting condition requiring medical treatment. Fetal ultrasound evaluation revealed severe congenital defects in four cases. There were no missed and no false positive diagnoses. Elective cesarean section (c-section) took place in 26/69 cases, 21/69 had a secondary c-section. Twenty-two out of 69 women delivered vaginally. Mean gestational age at delivery was 38(+6) gestational weeks. Pregnancy was complicated by macrosomia in 17/69 pregnancies. Severe neonatal hypoglycemia occurred in 6/69 cases. The number of deliveries by super-obese mothers showed no marked variation during the study period. In contrast the rate of deliveries by obese, but not super-obese, mothers showed an increase. Maternal super-obesity poses a high-risk situation for mother and child which generally demands a higher amount of perinatal care. The number of deliveries by super-obese mothers remained stable over the study period. Primary c-section was the most frequent mode of delivery. Of the parturients who opted for vaginal delivery nearly half of the deliveries had to be completed by secondary c-section. Over-all peripartal maternal complications did not exceed average.


Vascular surgery collaboration during pancreaticoduodenectomy with vascular reconstruction.
Once thought to have unresectable disease, pancreatic cancer patients with portal venous involvement are now reported to have comparable survival after pancreaticoduodenectomy (PD) with vascular reconstruction (VR) as compared with patients without vascular involvement. We hypothesize that a multidisciplinary approach involving a vascular surgeon will minimize morbidity and improve patency of VRs. We identified 204 patients who underwent PD for pancreatic adenocarcinoma from 1997 to 2008. Patients who underwent PD with VR (N = 42) were compared with those who underwent standard PD (N = 162). VRs were performed by a vascular surgeon and involved primary repair (N = 8), vein patch (N = 25), or interposition grafting (N = 9) with femoral or other venous conduit. Patients undergoing PD with VR had larger tumors (3.0 cm vs. 2.5 cm, P < 0.01) but did not have different rates of tumor-free margins (73% vs. 72%, P = 0.84) or lymph nodes metastases (50% vs. 38%, P = 0.14). The VR group had higher median blood loss (875 mL vs. 550 mL, P = 0<0.01), but no differences in mortality, complication rates, length of stay, or readmission rates were found in a median follow-up of 29 months. Overall survival rates were similar. Predictors of mortality on multivariate analysis included increasing histological grade (P = 0.01), positive lymph nodes (P = 0.01), and increasing tumor size (P = 0.01), but not VR (P = 0.28). When evaluated by computed tomography scans within 6 months postoperatively, 97% of reconstructions remained patent. The need for VR is not a contraindication to potentially curative resection in patients with pancreatic adenocarcinoma. Assistance of a vascular surgeon during VR may allow moderate-volume centers to achieve outcomes comparable with high-volume centers.


Acoustic radiation force impulse elastography for the evaluation of focal solid hepatic lesions: preliminary findings.
This study was designed to investigate the potential usefulness of acoustic radiation force impulse (ARFI) elastography to evaluate focal solid hepatic lesions. In total, 51 patients with 60 focal hepatic lesions, which included 17 hemangiomas, 25 hepatocellular carcinomas (HCCs), 15 metastases and three cholangiocarcinomas, underwent ARFI elastography. The lesions were classified into three groups: Group I consisted of metastatic liver tumors and cholangiocarcinomas, group II consisted of HCCs and group III consisted of hemangiomas. The stiffness and conspicuity of the tumors as depicted on ARFI elastography and the echogenicity and conspicuity of the tumors on corresponding B-mode images were analyzed. Shear wave velocity was obtained to quantify stiffness for 36 focal hepatic lesions: 11 hemangiomas, 17 HCCs and eight other malignant lesions. On ARFI elastography images, group I tumors (n=18) appeared stiffer than the background liver for 13 lesions (72%), softer for two lesions and had identical stiffness in three lesions compared with the background liver. For group II tumors (n=25), 13 lesions (52%) appeared stiffer than the liver, six lesions appeared softer than the liver and the remaining six lesions showed the same stiffness as the liver. For group III tumors (n=17), six lesions (35%) appeared stiffer than the liver, seven lesions appeared softer and the remaining four lesions showed the same stiffness as the liver. There were no statistical differences among the three groups in terms of tumor stiffness as seen on ARFI elastography images (p>0.05). Of the 60 lesions, 41 (68%) displayed a clearer or equivalent margin on the ARFI elastography compared with that seen on B-mode images. The shear wave velocities were: Group I, 2.18+/-0.96 m/s (mean value+/-SD); group II, 2.45+/-0.81m/s; group III, 1.51+/-0.71 m/s (p=0.012). With a cut-off value of 2m/s for the shear wave velocity, the positive predictive value and specificity for malignancy were 89% and 81%, respectively. Images obtained with ARFI elastography provided additional qualitative information regarding the stiffness and tumor margin of liver tumors. By measuring shear wave velocity, quantification of stiffness was made possible and showed the potential to differentiate malignant hepatic tumors from hepatic hemangiomas.


Subcalcaneal bursitis as the initial manifestation of rheumatoid arthritis: ultrasonographic observation of two cases.
In early rheumatoid arthritis (RA), proliferative synovitis sometimes occurs earlier in the tenosynovium or bursal synovium than in the articular synovium. Here we report two patients who presented with subcalcaneal bursitis while progressing from undifferentiated arthritis with high-titer anti-CCP antibodies (ACPA) to a diagnosis of RA. They had initially presented with palindromic transient pain in the hands and the feet. They were strongly positive for ACPA and negative for rheumatoid factor (RF) at the onset of symptoms. A few years later, they developed persistent plantar heel pain and underwent musculoskeletal ultrasonography (MSUS). MSUS revealed subcalcaneal bursitis with synovial proliferation. At that time, they became positive for RF and they were clinically diagnosed and began receiving treatment for RA. They developed overt synovitis in their wrists and fingers several months later. To the best of our knowledge, this is the first report on MSUS-detection of subcalcaneal bursitis with synovial proliferation in patients in the very early phase of RA, although there have been many reports of forefoot bursitis. These cases suggest that MSUS scanning of the plantar surface of the heel may be useful for patients with plantar heel pain who are suspected of having a very early phase of RA, because proliferative synovitis can be detected as subcalcaneal bursitis.


Does CBT facilitate emotional processing?
Cognitive Behavioural Therapy (CBT) is not primarily conceptualized as operating via affective processes. However, there is growing recognition that emotional processing plays an important role during the course of therapy. The Emotional Processing Scale was developed as a clinical and research tool to measure emotional processing deficits and the process of emotional change during therapy. Fifty-five patients receiving CBT were given measures of emotional functioning (Toronto Alexithymia Scale [TAS-20]; Emotional Processing Scale [EPS-38]) and psychological symptoms (Brief Symptom Inventory [BSI]) pre- and post-therapy. In addition, the EPS-38 was administered to a sample of 173 healthy individuals. Initially, the patient group exhibited elevated emotional processing scores compared to the healthy group, but after therapy, these scores decreased and approached those of the healthy group. This suggests that therapy ostensibly designed to reduce psychiatric symptoms via cognitive processes may also facilitate emotional processing. The Emotional Processing Scale demonstrated sensitivity to changes in alexithymia and psychiatric symptom severity, and may provide a valid and reliable means of assessing change during therapy.


Chitosan gold nanoparticles for detection of amplified nucleic acids isolated from sputum.
A platform for nucleic acid detection employing chitosan and chitosan coated gold nanoparticles (AuNPs) was developed. Mycobacterium tuberculosis (MTB) was used as a model target. MTB DNA was extracted from sputum using simple total nucleic acid extraction. Following amplification of MTB DNA, chitosan and AuNPs were added to samples. Free chitosan conjugated non-target DNA in negative samples, avoiding AuNP-DNA interaction and hence negative samples remained red. In positive samples, amplified DNA was capable of saturating free chitosan leading to AuNP aggregation where positive samples turned blue. Via visual color detection 15/16 MTB positive samples and 3/3 negative samples were correctly identified. This test is a 1-tube, 1-step assay reducing the risk of contamination in molecular laboratories and is a proof of concept on how chitosan; a cheap polymer could increase the sensitivity of AuNPs towards specific detection of nucleic acids without using target specific oligotargeters or expensive extraction kits.


Antioxidant Property of Jobelyn as the Possible Mechanism Underlying its Anti-amnesic Activity in Rodents.
Amnesia or loss of memory is the cardinal hallmark of Alzheimer's disease (AD), a progressive neurodegenerative disorder associated with ageing process. Although, AD had been discovered over a century ago, drugs which could cure or halt the progression of the disease are yet to see the light of the day. However, there has been a growing interest in the use of phytomedicines with multipronged mechanisms of action that could target various aspects of the pathologies of AD. Jobelyn (JB) is a potent antioxidant African polyherbal formulation with active components that have been acclaimed to show neuroprotection. This investigation was carried out to evaluate whether JB has anti-amnesic and antioxidant activities. The alteration of alternation behavior in the Y-maze paradigm was utilized as the test for memory function in mice. The effect of JB on acetylcholinesterase (AChE) activity, malondialdehyde (MDA) level and the concentrations of glutathione (GSH) in the frontal cortex and hippocampus were assessed in rats as means of providing insight into the mechanism underlying its anti-amnesic activity. The animals were given JB (1, 2.5 or 5mg/kg, i.p.) daily for 7 days before the biochemical assays or test for memory functions were carried out. JB was found to produce a significant increase in the level of alternation behavior compared with the control, suggesting anti-amnesic activity. Also, JB reversed the memory impairment induced by scopolamine, which further indicates anti-amnesic property. Furthermore, JB demonstrated a significant inhibition of MDA formation in the frontal cortex and hippocampus of rats, indicating antioxidant property. In addition, it increased the defense armory of the brain tissues, as it significantly increased the concentrations of GSH in the frontal cortex and hippocampus of rats. However, JB did not demonstrate any inhibitory effect against AChE activity in the frontal cortex and hippocampus of rats in comparison with the control group. This investigation provides evidence that suggests that JB has anti-amnesic and antioxidant properties. Although the present data suggest that the anti-amnesic property of JB might be related to its antioxidant activity, more studies are necessary to clarify this observation.


Endonasal endoscopic reoperation for residual or recurrent craniopharyngiomas.
OBJECTIVE Craniopharyngiomas can be difficult to remove completely based on their intimate relationship with surrounding visual and endocrine structures. Reoperations are not uncommon but have been associated with higher rates of complications and lower extents of resection. So radiation is often offered as an alternative to reoperation. The endonasal endoscopic transsphenoidal approach has been used in recent years for craniopharyngiomas previously removed with craniotomy. The impact of this approach on reoperations has not been widely investigated. METHODS The authors reviewed a prospectively acquired database of endonasal endoscopic resections of craniopharyngiomas over 11 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, performed by the senior authors. Reoperations were separated from first operations. Pre- and postoperative visual and endocrine function, tumor size, body mass index (BMI), quality of life (QOL), extent of resection (EOR), impact of prior radiation, and complications were compared between groups. EOR was divided into gross-total resection (GTR, 100%), near-total resection (NTR, > 95%), and subtotal resection (STR, < 95%). Univariate and multivariate analyses were performed. RESULTS Of the total 57 endonasal surgical procedures, 22 (39%) were reoperations. First-time operations and reoperations did not differ in tumor volume, radiological configuration, or patients' BMI. Hypopituitarism and diabetes insipidus (DI) were more common before reoperations (82% and 55%, respectively) compared with first operations (60% and 8.6%, respectively; p < 0.001). For the 46 patients in whom GTR was intended, rates of GTR and GTR+NTR were not significantly different between first operations (90% and 97%, respectively) and reoperations (80% and 100%, respectively). For reoperations, prior radiation and larger tumor volume had lower rates of GTR. Vision improved equally in first operations (80%) compared with reoperations (73%). New anterior pituitary deficits were more common in first operations compared with reoperations (51% vs 23%, respectively; p = 0.08), while new DI was more common in reoperations compared with first-time operations (80% vs 47%, respectively; p = 0.08). Nonendocrine complications occurred in 2 (3.6%) first-time operations and no reoperations. Tumor regrowth occurred in 6 patients (11%) over a median follow-up of 46 months and was not different between first versus reoperations, but was associated with STR (33%) compared with GTR+NTR (4%; p = 0.02) and with not receiving radiation after STR (67% vs 22%; p = 0.08). The overall BMI increased significantly from 28.7 to 34.8 kg/m2 over 10 years. Six months after surgery, there was a significant improvement in QOL, which was similar between first-time operations and reoperations, and negatively correlated with STR. CONCLUSIONS Endonasal endoscopic transsphenoidal reoperation results in similar EOR, visual outcome, and improvement in QOL as first-time operations, with no significant increase in complications. EOR is more impacted by tumor volume and prior radiation. Reoperations should be offered to patients with recurrent craniopharyngiomas and may be preferable to radiation in patients in whom GTR or NTR can be achieved.


1,4-phenylenebis(methylene)selenocyanate exerts exceptional chemopreventive activity in rat tongue carcinogenesis.
Among the organoselenium compounds, 1,4-phenylenebis(methylene) selenocyanate (p-XSC) is reported to exert the most effective chemopreventive effect on chemically induced carcinogenesis in the mammary glands, colon, and lung of laboratory animals. This study was designed to test the inhibitory effects of dietary p-XSC (5 and 15 ppm as selenium) during the initiation phase (1 week before, during, and up to 1 week after the carcinogen exposure) and the postinitiation phase (1 week after carcinogen administration until termination) on the formation of neoplasms of the tongue induced in male F344 rats by 4-nitroquinoline-1-oxide (4-NQO). The doses of p-XSC were 20% (5 ppm selenium) and 60% (15 ppm selenium) of maximum tolerated dose levels. At 6 weeks of age, all rats except those given p-XSC alone and those in untreated groups were treated with 4-NQO (20 ppm in the drinking water for 8 weeks). Dietary p-XSC, administered at selenium levels of 5 and 15 ppm during either the initiation or postinitiation phases, significantly reduced the incidence of carcinoma of the tongue. p-XSC was especially effective when it was administered at 15 ppm selenium during the postinitiation phase, in which case it completely inhibited the development of tongue carcinoma (from 47% in the dietary control to 0%). Glutathione S-transferase activities in the liver and tongue of rats treated with 4-NQO and p-XSC were significantly elevated compared to those in rats treated with 4-NQO alone. Similarly, quinone reductase activity was significantly elevated in the liver but decreased in the tongue (posterior portion). Such modulation by p-XSC in the phase II enzyme activities of the liver and tongue might be related to inhibition of the initiation. In addition, the expression of cell proliferation biomarkers, such as polyamine level, ornithine decarboxylase activity, 5-bromodeoxyuridin-labeling index, and argyrophilic nucleolar organizer's protein number, in the epithelium of the tongue was significantly reduced in rats that were fed thep-XSC diets compared to those who were fed the basal diet. Such alteration in cell proliferation through modulation of ornithine decarboxylase activity and polyamine biosynthesis in the tongue epithelium might be related to inhibition occurring in the postinitiation phase of carcinogenesis. The dose levels of p-XSC used induced no toxicity or alteration in body weight gain. Although the precise mechanisms of p-XSC-induced inhibition of tongue carcinogenesis remains to be elucidated, it is evident that p-XSC has powerful chemopreventive efficacy against tongue carcinogenesis.


Osteoporotic fractures in patients with systemic lupus erythematosus and end stage renal disease.
Background The incidence of end stage renal disease (ESRD) in patients with systemic lupus erythematosus (SLE) is rising. However, the relationship between osteoporotic fractures and SLE in the setting of ESRD remains uninvestigated. The purpose of this study was to compare the frequency of incident osteoporotic fractures in patients with ESRD with and without SLE, to identify risk factors for fractures in patients with SLE and ESRD, and to examine the contribution of these fractures to mortality. Methods Retrospective cohort study of patients with SLE ( n = 716) and a 5% random sample of controls without SLE ( n = 4176) in the United States Renal Data System (USRDS) from years 2006-2008 enrolled in Medicare Part D. Results Fractures occurred in 10.6% ( n = 76) of patients with SLE and ESRD and 12.1% ( n = 507) of patients with ESRD without SLE ( p = 0.24). Older age (adjusted relative risk 1.02, 95% confidence interval 1.01-1.04) was associated with an increased risk for fracture in patients with SLE and ESRD. In multivariable analyses, vertebral and hip fractures more than doubled the risk for mortality. Conclusions The frequency of osteoporotic fractures in patients with SLE and ESRD is similar to the general population of patients with ESRD. Vertebral and hip fractures are significant contributors to mortality in patients with SLE and ESRD. Fracture prevention, in particular, for elderly patients with SLE and ESRD, should be considered. Summary SLE is not an independent risk factor for fractures in patients with ESRD. However, among patients with SLE and ESRD, vertebral and hip fractures are significant contributors to mortality.


Presence of nanobacteria in psammoma bodies of ovarian cancer: evidence for pathogenetic role in intratumoral biomineralization.
The presence of laminated, calcified extracellular debris known as psammoma bodies is a well-known histomorphological feature of ovarian adenocarcinomas and other human malignancies. Biomineralization has recently been found to be associated with a group of extremely small Gram-negative bacteria capable of precipitating calcium salts. The aim of the present study was to evaluate a possible pathogenic link between the development of psammoma bodies and nanobacteria infection. Immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to analyse nanobacterial protein and gene expression in eight psammona body-containing adenocarcinomas and in 10 malignant ovarian tumours without signs of biomineralization. Nanobacterial proteins were detected in eight out of eight (100%) psammoma-positive tumour samples. Conversely, none of the 10 psammoma-negative tissues (0%) was positive for nanobacterial antigens. Furthermore, nanobacterial mRNA was detectable in all of the four tissues (100%) that contained psammoma bodies, but was absent in all 10 ovarian cystadenocarcinomas (0%) that were psammoma negative. We found a 100% concordance between the expression of nanobacteria and the presence of psammoma bodies in malignant ovarian tumours. Several lines of evidence suggest the involvement of these organisms in the process of biomineralization. We therefore conclude that nanobacterial infection of malignant ovarian tissue contributes to mechanisms leading to the formation of calcified deposits known as psammoma bodies.


World Antimalarial Resistance Network I: clinical efficacy of antimalarial drugs.
The proliferation of antimalarial drug trials in the last ten years provides the opportunity to launch a concerted global surveillance effort to monitor antimalarial drug efficacy. The diversity of clinical study designs and analytical methods undermines the current ability to achieve this. The proposed World Antimalarial Resistance Network (WARN) aims to establish a comprehensive clinical database from which standardised estimates of antimalarial efficacy can be derived and monitored over time from diverse geographical and endemic regions. The emphasis of this initiative is on five key variables which define the therapeutic response. Ensuring that these data are collected at the individual patient level in a consistent format will facilitate better data management and analytical practices, and ensure that clinical data can be readily collated and made amenable for pooled analyses. Such an approach, if widely adopted will permit accurate and timely recognition of trends in drug efficacy. This will guide not only appropriate interventions to deal with established multidrug resistant strains of malaria, but also facilitate prompt action when new strains of drug resistant plasmodia first emerge. A comprehensive global database incorporating the key determinants of the clinical response with in vitro, molecular and pharmacokinetic parameters will bring together relevant data on host, drug and parasite factors that are fundamental contributors to treatment efficacy. This resource will help guide rational drug policies that optimize antimalarial drug use, in the hope that the emergence and spread of resistance to new drugs can be, if not prevented, at least delayed.


A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter injection in the infarcted myocardium.
Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.


'Virus Carriers' and HIV testing: navigating Ukraine's HIV policies and programming for female sex workers.
There are an estimated 80,100 female sex workers (FSWs) in Ukraine, of whom 7% are living with HIV. Early HIV diagnosis continues to be a public health priority in Ukraine as only approximately 54% of people living with HIV are diagnosed nationwide. This study aims to analyse the content, context and discourse of HIV testing policies among female sex workers in Ukraine and how these policies are understood and implemented in practice. To analyse past and current national policies, we searched the database of the Ukrainian Parliament and the Ministry of Health for relevant policy documents (e.g. legislation and orders). To analyse the day-to-day practice of those involved in the implementation of these HIV programmes, we conducted face-to-face semi-structured interviews with key stakeholders. All data were coded using deductive thematic analysis initially guided by the Policy Triangle, a framework which addresses policy content, the process of policy-making, the health policy context, actors involved in policy formulation and implementation. HIV testing policies are formed and implemented in the post-Soviet context through a vertical system of AIDS clinics, resulting in the separation of key affected populations from the rest of the health system. Successive testing policies have been strongly influenced by international donors and non-governmental organisations. Furthermore, a lack of government funding for HIV prevention created a gap that international donors and local non-governmental organisations covered to ensure the implementation of testing policies. Their role, however, had limited influence on the Ukrainian government to increase funding for prevention, including testing of FSWs. Since the early 1990s, when stigmatising and discriminatory forced/mandatory HIV testing was applied, these approaches were slowly replaced with voluntary testing, self-testing and assisted HIV testing, yet stigma was found to be a barrier among FSWs to access testing. Poor governance and the fragmentation of the health system, ongoing health sector reforms, shrinking international funding, and persisting stigma towards people living with HIV and sex workers might impede the continuity and sustainability of HIV testing programmes. Local civil society may now have the opportunity to contribute to the development and further implementation of HIV testing policies in Ukraine.


Chronotype is associated with the timing of the circadian clock and sleep in toddlers.
Chronotype is a construct reflecting individual differences in diurnal preference. Although chronotype has been studied extensively in school-age children, adolescents and adults, data on young children are scarce. This study describes chronotype and its relationship to the timing of the circadian clock and sleep in 48 healthy children aged 30-36 months (33.4 ± 2.1 months; 24 males). Parents completed the Children's Chronotype Questionnaire (CCTQ) ~2 weeks before the start of the study. The CCTQ provides three measures of chronotype: midsleep time on free days, a multi-item morningness/eveningness score and a single item chronotype score. After 5 days of sleeping on their habitual schedule (assessed with actigraphy and sleep diaries), children participated in an in-home salivary dim light melatonin onset assessment. Average midsleep time on free days was 1:47 ± 0:35, and the average morningness/eveningness score was 26.8 ± 4.3. Most toddlers (58.4%) were rated as 'definitely a morning type' or 'rather morning than evening type', while none (0%) were rated as 'definitely evening type'. More morning types (midsleep time on free days and morningness/eveningness score, respectively) had earlier melatonin onset times (r = 0.45, r = 0.26), earlier habitual bedtimes (r = 0.78, r = 0.54), sleep onset times (r = 0.80, r = 0.52), sleep midpoint times (r = 0.90, r = 0.53) and wake times (r = 0.74, r = 0.34). Parent ratings using the single-item chronotype score were associated with melatonin onset (r = 0.32) and habitual bedtimes (r = 0.27), sleep onset times (r = 0.33) and sleep midpoint times (r = 0.27). Morningness may best characterize circadian preference in early childhood. Associations between chronotype and circadian physiology and sleep timing suggest adequate validity for the CCTQ in this age group. These findings have important implications for understanding the marked variability in sleep timing during the early years of life.


Differences in transcription between free-living and CO2-activated third-stage larvae of Haemonchus contortus.
The disease caused by Haemonchus contortus, a blood-feeding nematode of small ruminants, is of major economic importance worldwide. The infective third-stage larva (L3) of this gastric nematode is enclosed in a cuticle (sheath) and, once ingested with herbage by the host, undergoes an exsheathment process that marks the transition from the free-living (L3) to the parasitic (xL3) stage. This study explored changes in gene transcription associated with this transition and predicted, based on comparative analysis, functional roles for key transcripts in the metabolic pathways linked to larval development. Totals of 101,305 (L3) and 105,553 (xL3) expressed sequence tags (ESTs) were determined using 454 sequencing technology, and then assembled and annotated; the most abundant transcripts encoded transthyretin-like, calcium-binding EF-hand, NAD(P)-binding and nucleotide-binding proteins as well as homologues of Ancylostoma-secreted proteins (ASPs). Using an in silico-subtractive analysis, 560 and 685 sequences were shown to be uniquely represented in the L3 and xL3 stages, respectively; the transcripts encoded ribosomal proteins, collagens and elongation factors (in L3), and mainly peptidases and other enzymes of amino acid catabolism (in xL3). Caenorhabditis elegans orthologues of transcripts that were uniquely transcribed in each L3 and xL3 were predicted to interact with a total of 535 other genes, all of which were involved in embryonic development. The present study indicated that some key transcriptional alterations taking place during the transition from the L3 to the xL3 stage of H. contortus involve genes predicted to be linked to the development of neuronal tissue (L3 and xL3), formation of the cuticle (L3) and digestion of host haemoglobin (xL3). Future efforts using next-generation sequencing and bioinformatic technologies should provide the efficiency and depth of coverage required for the determination of the complete transcriptomes of different developmental stages and/or tissues of H. contortus as well as the genome of this important parasitic nematode. Such advances should lead to a significantly improved understanding of the molecular biology of H. contortus and, from an applied perspective, to novel methods of intervention.


Vocal emotion processing in Parkinson's disease: reduced sensitivity to negative emotions.
To document the impact of Parkinson's disease (PD) on communication and to further clarify the role of the basal ganglia in the processing of emotional speech prosody, this investigation compared how PD patients identify basic emotions from prosody and judge specific affective properties of the same vocal stimuli, such as valence or intensity. Sixteen non-demented adults with PD and 17 healthy control (HC) participants listened to semantically-anomalous pseudo-utterances spoken in seven emotional intonations (anger, disgust, fear, sadness, happiness, pleasant surprise, neutral) and two distinct levels of perceived emotional intensity (high, low). On three separate occasions, participants classified the emotional meaning of the prosody for each utterance (identification task), rated how positive or negative the stimulus sounded (valence rating task), or rated how intense the emotion was expressed by the speaker (intensity rating task). Results indicated that the PD group was significantly impaired relative to the HC group for categorizing emotional prosody and showed a reduced sensitivity to valence, but not intensity, attributes of emotional expressions conveying anger, disgust, and fear. The findings are discussed in light of the possible role of the basal ganglia in the processing of discrete emotions, particularly those associated with negative vigilance, and of how PD may impact on the sequential processing of prosodic expressions.


Self-organization of the human embryo in the absence of maternal tissues.
Remodelling of the human embryo at implantation is indispensable for successful pregnancy. Yet it has remained mysterious because of the experimental hurdles that beset the study of this developmental phase. Here, we establish an in vitro system to culture human embryos through implantation stages in the absence of maternal tissues and reveal the key events of early human morphogenesis. These include segregation of the pluripotent embryonic and extra-embryonic lineages, and morphogenetic rearrangements leading to generation of a bilaminar disc, formation of a pro-amniotic cavity within the embryonic lineage, appearance of the prospective yolk sac, and trophoblast differentiation. Using human embryos and human pluripotent stem cells, we show that the reorganization of the embryonic lineage is mediated by cellular polarization leading to cavity formation. Together, our results indicate that the critical remodelling events at this stage of human development are embryo-autonomous, highlighting the remarkable and unanticipated self-organizing properties of human embryos.


A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease.
We reviewed case-control studies of diffusion tensor imaging (DTI) in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI), in order to establish the relative severity and location of white matter microstructural changes. EMBASE and MEDLINE were searched using the keywords, (["diffusion tensor"] and ["Alzheimer*" or "mild cognitive impairment"]), as were reference lists of relevant papers. Forty-one diffusion tensor imaging studies contained data that were suitable for inclusion. Group means and standard deviations for fractional anisotropy and mean diffusivity, or p values from 2-sample tests, were extracted and pooled, using standard methods of meta-analysis and metaregression. Fractional anisotropy was decreased in AD in all regions except parietal white matter and internal capsule, while patients with MCI had lower values in all white matter regions except parietally and occipitally. Mean diffusivity was increased in AD in all regions, and in MCI in all but occipital and frontal regions.


Effects of holistic nursing course: a paradigm shift for holistic health practices.
A study of an undergraduate course in holistic nursing was conducted to determine its impact on personal and professional health care practices. A mixed method design was used to examine responses on a sample of 200 participants. Results indicated a positive personal impact with continued application of concepts into professional health practices. Personal and professional nursing practices were influenced from 1 to 7 years after completing the holistic nursing course. After introduction of the concepts of self-care and holistic approaches to health, students and graduates experienced a shift in values and beliefs related to their own health practices. Continued exposure to holistic practices creates a pattern of awareness toward health that affects future personal and professional nursing practice, creating a paradigm shift for emerging nursing students and graduates from the course. This affects the manner in which nurses meet the needs of their clients in a variety of settings.


Non-toxic agarose/gelatin-based microencapsulation system containing gallic acid for antifungal application.
Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.


Regulation by IL-5 of expression of functional platelet-activating factor receptors on human eosinophils.
Platelet-activating factor (PAF) and IL-5 are both important mediators of various allergic reactions, although the relationship between these mediators in allergic responses has not yet been fully elucidated. In this study, we investigated the effects of human rIL-5 on the expression of the PAF receptor (PAF-R) on eosinophils from healthy human volunteers. The specific binding of [3H]WEB 2086, a specific ligand for PAF-R, to eosinophils treated with 5 ng/ml of IL-5 for 12 h was significantly higher than that to untreated cells. The Bmax value for IL-5-treated eosinophils was 1.8-fold higher than that for untreated cells, while the Kd values remained unchanged. This clearly indicates that surface expression of PAF-R on eosinophils is enhanced by IL-5. The enhancement was first observed at 6 h and reached a plateau at 12 to 18 h. The effect of IL-5 was abolished in the presence of cycloheximide or actinomycin D. When the relative amount of PAF-R mRNA was determined by reverse transcription PCR, the message was found to be increased through activation of transcription of transcript 1 on exposure to IL-5. Furthermore, we found that the PAF-induced increase in intracellular calcium ion concentration in eosinophils was markedly augmented by exposure to IL-5 for 12 h. Several lines of data suggest that the enhanced expression of PAF-R on eosinophils due to IL-5 is the cause of the augmented response to PAF. These findings will be of value for understanding the mechanisms of selective infiltration and activation of eosinophils in allergic diseases in which PAF and IL-5 are crucially involved.


Agreement in the classification and treatment of the superior labrum.
The Snyder classification scheme is the most commonly used system for classifying superior labral injuries. Although this scheme is intended to be used for arthroscopic visual classification only, it is thought that other nonarthroscopic historical variables also influence the classification. This study was conducted to evaluate the intrasurgeon and intersurgeon agreement in classifying variable presentations of the superior labrum and to evaluate the influence of clinical variables on the classification and treatment choices of surgeons. Cohort study (diagnosis); Level of evidence, 3. A group of arthroscopic shoulder surgeons were asked to rank in order of importance clinical variables considered in diagnosing and treating the superior labrum. The surgeons then watched 50 arthroscopic videos of the superior labrum, ranging from normal to pathologic, on 3 different occasions. The first and third viewings were accompanied by no clinical information. The second viewing was accompanied by a detailed clinical vignette for each video. The surgeons selected a classification and treatment for each video. A patient's job/sport, age, and physical examination findings were considered the most important clinical variables surgeons consider during management of the superior labrum. Comparing the 2 viewings without clinical information, surgeons selected a different classification 28.5% of the time from the first to the second time. A different classification was chosen 71.5% of the time when the surgeon was supplied a clinical vignette at the subsequent viewing. Similarly, the treatment selected changed in 36% and 69.1% of cases when viewed again without vignettes and with vignettes, respectively. Intersurgeon agreement was moderate without clinical vignettes and fair with vignettes. Historical, physical examination, and surgical observations were found to influence the odds of change of classification. There is significant intrasurgeon and intersurgeon variability in classification and treatment of the superior labrum. Clinical historical, examination, and surgical findings influence classification and treatment choices.


Prevalence of psychiatric disorders in children and adolescents with and without intellectual disability.
There have been very few population-based studies of the prevalence of psychiatric disorders among children and adolescents with and without intellectual disability (ID). Secondary analysis of the 1999 Office for National Statistics survey of the Mental Health of Children and Adolescents in Great Britain was performed. This survey collected information on a multistage, stratified, random sample of 10 438 children between 5 and 15 years of age across 475 postcode sectors in England, Scotland and Wales. The prevalence of any diagnosed ICD-10 disorder, conduct disorder, anxiety disorder, hyperkinesis and pervasive developmental disorders were significantly greater among children with ID than among their non-ID peers. There were no statistically significant differences between children with and without ID with regard to the prevalence of depressive disorders, eating disorders or psychosis. Factors associated with an increased risk of psychopathology among children and adolescents with ID included age, gender, social deprivation, family composition, number of potentially stressful life events, the mental health of the child's primary carer, family functioning and child management practices. Children and adolescents with ID are at significantly increased risk of certain forms of psychiatric disorder. Careful consideration of the social and economic adversity facing such families will be necessary to ensure that support services are responsive to both the needs of child as well as the needs of the family in which they are living.


Cryptoanalysis on optical image encryption systems based on the vector decomposition technique in the Fourier domain.
In this paper, the security of optical cryptosystems based on the vector decomposition technique in the Fourier domain is analyzed. Compared to the conventional cryptosystem based on the equal modulus decomposition (EMD) technique, an additional EMD structure is introduced in the cascaded EMD-based cryptosystem; hence, the mask including the phase information of the Fourier spectrum is further encoded in the second EMD structure to enhance the security level. However, it is shown that the number of the private keys has not been increased in the cascaded EMD-based cryptosystem, which makes it possible to crack the cascaded EMD-based cryptosystem. Therefore, a chosen-plaintext attack (CPA) and a special attack with an arbitrarily given private key are proposed to retrieve information from encoded images obtained by the cascaded EMD-based cryptosystem. In addition, the security of the cryptosystem based on the random modulus decomposition (RMD) technique is also analyzed. Compared to the EMD-based cryptosystem in which the Fourier spectrum is decomposed into two vectors with equal moduli, the security level of the cryptosystem has been improved by using the RMD technique to decompose the spectrum into vectors with unequal moduli to decrease the number of the amplitude constraints. However, it is found that the arbitrarily given ciphertext provides the attackers enough information to retrieve the precise information of the plaintext without any knowledge of the private keys. A special attack is proposed to crack the RMD-based cryptosystem. This is the first time to report that these two cryptosystems based on the vector decomposition technique are attacked successfully. Numerical simulation is conducted to validate the feasibility and effectiveness of the proposed attacks.


Three-dimensional left ventricular segmentation from magnetic resonance imaging for patient-specific modelling purposes.
To propose a nearly automated left ventricular (LV) three-dimensional (3D) surface segmentation procedure, based on active shape modelling (ASM) and built on a database of 3D echocardiographic (3DE) LV surfaces, for cardiac magnetic resonance (CMR) images, and to test its accuracy for LV volumes computation compared with 'gold standard' manual tracings and discs-summation method. The ASM was created based on segmented LV surfaces (4D LV analysis, Tomtec) from 3DE datasets of 205 patients. Then, it was applied to the cardiac magnetic resonance imaging short-axis (SAX) images stack of 12 consecutive patients. After proper realignment using two- and four-chambers CMR long-axis views both as reference and for initializing LV apex and base (six points in total), the ASM was iteratively and automatically updated to match the information of all the SAX planes contemporaneously, resulting in an endocardial LV 3D mesh from which volume was directly derived. The same CMR images were analysed by an experienced cardiologist to derive end-diastolic and end-systolic volumes. Linear correlation and Bland-Altman analyses were applied vs. the manual 'gold standard'. Active shape modelling results showed high correlations with manual values both for LV volumes (r(2) > 0.98) and ejection fraction (EF) (r(2) > 0.90), non-significant biases and narrow limits of agreement. The proposed method resulted in accurate detection of 3D LV endocardial surfaces, which lead to fast and reliable measurements of LV volumes and EF when compared with manual tracing of CMR SAX images. The segmented 3D mesh, including a realistic LV apex and base, could constitute a novel starting point for more realistic patient-specific finite element modelling.


Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.
Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).


An extended grammar system for learning and recognizing complex visual events.
For a grammar-based approach to the recognition of visual events, there are two major limitations that prevent it from real application. One is that the event rules are predefined by domain experts, which means huge manual cost. The other is that the commonly used grammar can only handle sequential relations between subevents, which is inadequate to recognize more complex events involving parallel subevents. To solve these problems, we propose an extended grammar approach to modeling and recognizing complex visual events. First, motion trajectories as original features are transformed into a set of basic motion patterns of a single moving object, namely, primitives (terminals) in the grammar system. Then, a Minimum Description Length (MDL) based rule induction algorithm is performed to discover the hidden temporal structures in primitive stream, where Stochastic Context-Free Grammar (SCFG) is extended by Allen's temporal logic to model the complex temporal relations between subevents. Finally, a Multithread Parsing (MTP) algorithm is adopted to recognize interesting complex events in a given primitive stream, where a Viterbi-like error recovery strategy is also proposed to handle large-scale errors, e.g., insertion and deletion errors. Extensive experiments, including gymnastic exercises, traffic light events, and multi-agent interactions, have been executed to validate the effectiveness of the proposed approach.


Aberrant energy metabolism and redox balance in seizure onset zones of epileptic patients.
Epilepsy is a disorder that affects around 1% of the population. Approximately one third of patients do not respond to anti-convulsant drugs treatment. To understand the underlying biological processes involved in drug resistant epilepsy (DRE), a combination of proteomics strategies was used to compare molecular differences and enzymatic activities in tissue implicated in seizure onset to tissue with no abnormal activity within patients. Label free quantitation identified 17 proteins with altered abundance in the seizure onset zone as compared to tissue with normal activity. Assessment of oxidative protein damage by protein carbonylation identified additional 11 proteins with potentially altered function in the seizure onset zone. Pathway analysis revealed that most of the affected proteins are involved in energy metabolism and redox balance. Further, enzymatic assays showed significantly decreased activity of transketolase indicating a disruption of the Pentose Phosphate Pathway and diversion of intermediates into purine metabolic pathway, resulting in the generation of the potentially pro-convulsant metabolites. Altogether, these findings suggest that imbalance in energy metabolism and redox balance, pathways critical to proper neuronal function, play important roles in neuronal network hyperexcitability and can be used as a primary target for potential therapeutic strategies to combat DRE. SIGNIFICANCE: Epileptic seizures are some of the most difficult to treat neurological disorders. Up to 40% of patients with epilepsy are resistant to first- and second-line anticonvulsant therapy, a condition that has been classified as refractory epilepsy. One potential therapy for this patient population is the ketogenic diet (KD), which has been proven effective against multiple refractory seizure types However, compliance with the KD is extremely difficult, and carries severe risks, including ketoacidosis, renal failure, and dangerous electrolyte imbalances. Therefore, identification of pathways disruptions or shortages can potentially uncover cellular targets for anticonvulsants, leading to a personalized treatment approach depending on a patient's individual metabolic signature.


Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis.
Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots. Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01). The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research. None.


The origin of mean arterial and jugular venous blood pressures in giraffes.
Using a mechanical model of the giraffe neck and head circulation consisting of a rigid, ascending, 'carotid' limb, a 'cranial' circulation that could be rigid or collapsible, and a descending, 'jugular' limb that also could be rigid or collapsible, we have analyzed the origin of the high arterial and venous pressures in giraffe, and whether blood flow is assisted by a siphon. When the tubes were rigid and the 'jugular' limb exit was lower than the 'carotid' limb entrance a siphon operated, 'carotid' hydrostatic pressures became more negative, and flow was 3.3 l min(-1) but ceased when the 'cranial' and 'jugular' limbs were collapsible or when the 'jugular' limb was opened to the atmosphere. Pumping water through the model produced positive pressures in the 'carotid' limb similar to those found in giraffe. Applying an external 'tissue' pressure to the 'jugular' tube during pump flow produced the typical pressures found in the jugular vein in giraffe. Constriction of the lowest, 'jugular cuff', portion of the 'jugular' limb showed that the cuff may augment the orthostatic reflex during head raising. Except when all tubes were rigid, pressures were unaffected by a siphon. We conclude that mean arterial blood pressure in giraffes is a consequence of the hydrostatic pressure generated by the column of blood in the neck, that tissue pressure around the collapsible jugular vein produces the known jugular pressures, and that a siphon does not assist flow through the cranial circulation.


Elimination of Hepatitis C in Liver Transplant Recipients.
Background and Aims: Recurrent hepatitis C (HCV) disease in liver transplant (LT) recipients is associated with significant morbidity and mortality. With the availability of noninterferon-based therapy, eliminating HCV may be achievable in LT recipients. Methods: We studied all consecutive recipients who underwent LT at the University of California Los Angeles between January 2005 and June 2017. We collected data on date of transplant and last follow-up, as well as laboratory values. We also recorded type and timing of antiviral therapy relative to LT. Analyses were performed to assess the proportion of LT recipients who are viremic after transplant. Results: Six hundred thirty-four patients underwent LT with a diagnosis of HCV. There was a statistically significant trend for patients to be cured before (p < 0.001) and after liver transplantation (p < 0.001) for the study period of 2014 to 2016 relative to 2005 and 2013, respectively. Of the 634 recipients eligible for therapy, 8% and 74% were treated within 12 months of transplant for the study periods 2005 to 2013 and 2014 to 2016, respectively. There was a significant decrease between the two study periods in the proportion of patients undergoing re-LT 1 year after the original LT: 5.5% (n = 28/510) and 1.5% (n = 2/124) respectively for study periods 2005 to 2013 and 2014 to 2016 respectively (p = 0.011). Conclusions: The proportion of LT recipients who are viremic has decreased over time. Eliminating HCV in LT recipients is feasible after the introduction of direct-acting agents. Curing HCV should translate to improved clinical outcomes in LT recipients who were transplanted for HCV infection with longer follow-up. Preliminary results suggest the decreased need for transplant in the direct-acting agents era.


Lack of infection with XMRV or other MLV-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals.
Autistic spectrum disorder (ASD) is characterized by impaired language, communication and social skills, as well as by repetitive and stereotypic patterns of behavior. Many autistic subjects display a dysregulation of the immune system which is compatible with an unresolved viral infection with prenatal onset, potentially due to vertical viral transmission. Recently, the xenotropic murine leukemia virus-related virus (XMRV) has been implicated in chronic fatigue syndrome (CFS) and in prostate cancer by several, though not all studies. We assessed whether XMRV or other murine leukemia virus (MLV)-related viruses are involved in autistic disorder. Using nested PCR targeted to gag genomic sequences, we screened DNA samples from: (i) peripheral blood of 102 ASD patients and 97 controls, (ii) post-mortem brain samples of 20 ASD patients and 17 sex- and age-matched controls, (iii) semen samples of 11 fathers of ASD children, 25 infertile individuals and 7 fertile controls. No XMRV gag DNA sequences were detected, whereas peripheral blood samples of 3/97 (3.1%) controls were positive for MLV. CONCLUSIONS| No MLV-related virus was detected in blood, brain, and semen samples of ASD patients or fathers. Hence infection with XMRV or other MLV-related viruses is unlikely to contribute to autism pathogenesis.


Child deaths due to injury in the four UK countries: a time trends study from 1980 to 2010.
Injuries are an increasingly important cause of death in children worldwide, yet injury mortality is highly preventable. Determining patterns and trends in child injury mortality can identify groups at particularly high risk. We compare trends in child deaths due to injury in four UK countries, between 1980 and 2010. We obtained information from death certificates on all deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and resident in England, Scotland, Wales or Northern Ireland. Injury deaths were defined by an external cause code recorded as the underlying cause of death. Injury mortality rates were analysed by type of injury, country of residence, age group, sex and time period. Child mortality due to injury has declined in all countries of the UK. England consistently experienced the lowest mortality rate throughout the study period. For children aged 10 to 18 years, differences between countries in mortality rates increased during the study period. Inter-country differences were largest for boys aged 10 to 18 years with mortality rate ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91) for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England (the baseline) in 2006-10. The decline in mortality due to injury was accounted for by a decline in unintentional injuries. For older children, no declines were observed for deaths caused by self-harm, by assault or from undetermined intent in any UK country. Whilst child deaths from injury have declined in all four UK countries, substantial differences in mortality rates remain between countries, particularly for older boys. This group stands to gain most from policy interventions to reduce deaths from injury in children.


Development of diabetogenic T cells from NOD/Lt marrow is blocked when an allo-H-2 haplotype is expressed on cells of hemopoietic origin, but not on thymic epithelium.
Diabetes is a T cell-mediated process in NOD/Lt mice, with a major genetically recessive component of susceptibility linked to homozygous expression of the unique H-2g7 MHC haplotype. Heterozygous expression of the H-2nb1 haplotype derived from the NON/Lt strain confers diabetes resistance both in (NOD x NON)F1 hybrids and in NOD mice congenic for the H-2nb1 haplotype. However, diabetes resistance is abrogated in F1 hybrids by NOD/Lt bone marrow reconstitution. To establish whether the generation of beta cell autoreactive T cells from NOD/Lt bone marrow-derived precursors required at least heterozygous expression of the H-2g7 haplotype on thymic epithelium, adolescent thymectomized (NOD x NON)F1 mice were implanted with neonatal NON/Lt thymus grafts before lethal radiation and reconstitution with NOD/Lt bone marrow. Peripheral T cells maturing through this ectopic thymic implant exclusively expressed the NOD H-2g7 haplotype and were tolerant to H-2nb1 skin grafts. Nevertheless, diabetes developed in 32% of the NON/Lt thymus-grafted chimeras vs 38% of the sham-thymectomized NOD bone marrow chimeras. Thus, homozygous expression of the diabetes-resistant H-2nb1 haplotype on thymic epithelium failed to block development of a diabetogenic T cell repertoire. To examine if expression of H-2nb1 on hemopoietically derived APC could alter the diabetogenic potential of NOD/Lt marrow, diabetes-resistant NOD.NON-H-2nb1 congenic mice were mated with NOD/Lt mice to produce NOD-H-2g7/H-2nb1 heterozygous recipients. These were lethally irradiated and reconstituted with either NOD/Lt marrow alone, NOD.H-2nb1 homozygous congenic marrow alone, or a 1:1 mixture of the two marrow populations. By 25 wk of age, all of the MHC heterozygous recipients of NOD.NON-H-2nb1 marrow remained diabetes-free whereas 75% of the MHC heterozygous recipients of NOD/Lt marrow developed diabetes. A striking decrease in diabetes was observed when T cell precursors derived from NOD/Lt marrow interacted with H-2nb1 gene products on hemopoietically derived APC, inasmuch as only 7% of the MHC heterozygous recipients reconstituted with a 1:1 mixture of NOD/Lt and NOD.NON-H-2nb1 marrow developed diabetes. Peripheral leukocytes in all reconstitution classes expressed the MHC phenotype(s) of the marrow donor(s). Skin grafting confirmed that all reconstitution classes of MHC heterozygous recipients were tolerant to the H-2nb1 haplotype.(ABSTRACT TRUNCATED AT 400 WORDS)


Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.
Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering.


Eosinophil percentage as a new prognostic marker in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.
In addition to proinflammatory properties, eosinophils can stimulate platelet activation and enhance prothrombotic pathways. In this study, we aimed to investigate the association between the eosinophil percentage (EOS%) and major adverse cardiac events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI). This study enrolled a total of 1,909 patients who were diagnosed with STEMI. Ventricular arrhythmia, reinfarction, the need for cardiopulmonary resuscitation, target vessel revascularization, congestive heart failure, and cardiovascular mortality during index hospitalization were defined as MACE. Three hundred and eighty patients (19.7%) reached the combined endpoint with MACE. The rates of inhospital mortality and MACE were significantly higher in low EOS% group as compared to high EOS% group (4% vs. 1.1%, p < 0.01 and 32.8% vs. 11.3%, p < 0.01, respectively). On multivariate logistic regression analyses, EOS% (OR = 0.44, p < 0.01) was found to be one of the independent predictors of MACE. The EOS% lower than 0.60 on admission predicted inhospital MACE with a sensitivity of 68% and a specificity of 72% (AUC: 0.684, p < 0.01). Low EOS% on admission may be associated with high inhospital MACE in STEMI patients. EOS% may be used as a novel biomarker for risk stratification of these patients.


A retrospective study to assess clinical characteristics and time to initiation of open-triple therapy among patients with chronic obstructive pulmonary disease, newly established on long-acting mono- or combination therapy.
An incremental approach using open-triple therapy may improve outcomes in patients with chronic obstructive pulmonary disease (COPD). However, there is little sufficient, real-world evidence available identifying time to open-triple initiation. This retrospective study of patients with COPD, newly initiated on long-acting muscarinic antagonist (LAMA) monotherapy or inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination therapy, assessed baseline demographics, clinical characteristics, and exacerbations during 12 months prior to first LAMA or ICS/LABA use. Time to initiation of open-triple therapy was assessed for 12 months post-index date. Post hoc analyses were performed to assess the subsets of patients with pulmonary-function test (PFT) information and patients with and without comorbid asthma. Demographics and clinical characteristics were similar between cohorts in the pre-specified and post hoc analyses. In total, 283 (19.3%) and 160 (10.9%) patients had moderate and severe exacerbations at baseline, respectively, in the LAMA cohort, compared with 482 (21.3%) and 289 (12.8%) patients in the ICS/LABA cohort. Significantly more patients initiated open-triple therapy in the LAMA cohort compared with the ICS/LABA cohort (226 [15.4%] versus 174 [7.7%]; P<0.001); results were similar in the post hoc analyses. Mean (standard deviation) time to open-triple therapy was 79.8 (89.0) days in the LAMA cohort and 122.9 (105.4) days in the ICS/LABA cohort (P<0.001). This trend was also observed in the post hoc analyses, though the difference between cohorts was nonsignificant in the subset of patients with PFT information. In this population, patients with COPD are more likely to initiate open-triple therapy following LAMA therapy, compared with ICS/LABA therapy. Further research is required to identify factors associated with the need for treatment augmentation among patients with COPD.


Risk reduction of adverse effects due to di-(2-ethylhexyl) phthalate (DEHP) by utilizing microbial degradation.
Di-(2-ethylhexyl) phthalate (DEHP), one of the major phthalates, was reported to be a suspected endocrine-disrupting chemical (EDC) that might produce developmental or reproductive toxicities. Therefore, much effort was undertaken to reduce the potential risk of adverse effects of DEHP on humans by diminishing environmental exposure to this chemical. A bacterium was isolated from soil contaminated with DEHP at a poly(vinyl chloride) (PVC) manufacturing site. Biodegradation kinetic experiments on DEHP-contaminated soil samples were performed in a slurry phase system. The DEHP concentration was decreased to a concentration of 0.5 g/kg by the addition of 1% culture medium to the soil. The microorganism degraded DEHP through the formation of a mono-2-ethylhexyl phthalate (MEHP), which was subsequently metabolized to phthalic acid (PA), as detected by GC-MS analysis. Micrococcus luteus was able to degrade almost 90% of the initial DEHP within 12 d. In addition, the microbial toxicity study of DEHP and its degradation products MEHP or PA, using recombinant bioluminescent bacteria, showed that PA or the mixture produced protein or DNA damage. Data thus suggest that a new strain of Micrococcus luteus with a strong ability to degrade DEHP into nontoxic metabolites may contribute to decontamination of environmental phthalates and consequently risk reduction of human exposure to DEHP.


Intracellular traffic and fate of protein transduction domains HIV-1 TAT peptide and octaarginine. Implications for their utilization as drug delivery vectors.
Transduction domains such as those derived from the HIV-TAT protein are candidate vectors for intracellular delivery of therapeutic macromolecules such as DNA and proteins. The mechanism by which they enter cells is controversial, and very little spatial information regarding the downstream fate of these peptides from the plasma membrane is available. We studied endocytic traffic of fluorescent conjugates of HIV-TAT peptide and octaarginine in human hematopoietic cell lines K562 (CD34-) and KG1a (CD34+) and substantiated our findings in epithelia cells. Both peptides were efficiently internalized to endocytic pathways of both hematopoietic cell lines; however, comparative analysis of the intracellular location of the peptides with endocytic probes revealed major differences in spatial organization of their endocytic organelles and their interaction with the peptides at low temperatures. Double labeling confocal microscopy demonstrates that prelabeled lysosomes of all the tested cells are accessible to internalized peptides within 60 min of endocytic uptake. Incubation of cells with nocodazole and cytochalasin D inhibited peptide traffic from early to late endosomal structures, demonstrating a cytoskeletal requirement for lysosomal delivery. Disruption of Golgi and endoplasmic reticulum dynamics was without effect on peptide localization, suggesting that endosomes and lysosomes rather than these organelles are the major acceptor compartments for these molecules.


Chronobiologic quantification of nocturnal low-dose dopamine effect on circadian rhythms of thyroid-related hormones and prolactin (PRL).
Six clinically-healthy young men provided plasma samples every 30 min for 24 h (from 09:00-09:00 on 2 occasions. TSH, free T3 and free T4 were determined in the 30-min samples, while prolactin was determined in samples 1-3h apart. During the first test span, each man received an infusion of physiologic saline between 21(00)-01(00). Upon re-sampling several weeks later, 3 men received a low dose of dopamine (0.1 microgram/kg/min) and 3 men received a high dose (1.0 microgram) over the same hours (21:00-01:00). The least-squares fit of a 24-h cosine to each data series described a statistically-significant circadian rhythm (p less than 0.01) for each subject on each day of study. While overall group comparisons revealed no significant difference in mesor for any hormone studied, some intra-individual differences in rhythm parameters between saline and dopamine infusion were found. Dopamine Rx produced a statistically-significant increase in amplitude for PRL and T4 and an advance in acrophase for TSH, T3 and T4, but a delay for PRL. Studies measuring hormones of interest for the 24th immediately preceding and the 24th immediately following dopamine infusion at varying circadian stages (rather than only between 21:00-01:00) are warranted and have to be individualized--one of the points of this paper. The other main point is that data reduction to a mean and a standard deviation entails loss of information that can be recovered by chronobiologic methods, here used only as a model, in view of the limitations of the sampling design on hand.


Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.
Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.


Intraoperative use of mitomycin C in fibrous atresia of the external auditory canal.
The ability of mitomycin C to inhibit fibroblasts in vitro has prompted its use during standard surgical procedures as a means of preventing the development of adhesions and stenosis. We conducted a prospective study to evaluate the effectiveness of topical mitomycin C in maintaining an open external auditory canal in 6 ears of 4 patients with aural fibrotic atresia who were undergoing meatoplasty. During the procedure, we applied 1 ml of mitomycin C (0.4 mg/ml) for 4 minutes to the external auditory canal (in 1 case, mitomycin C was reapplied to an ear 1 month later). Between 3 and 14 months postoperatively, the patency of the ear canal was assessed visually and hearing was evaluated audiometrically. Adequate patency was achieved in 5 of the 6 ears (83.3%), and the air-bone gap in these 5 ears had improved to 10 dB or less. No postoperative complications or sensorineural hearing loss was observed. In this very limited number of cases, we found that the intraoperative use of mitomycin C appeared to have been helpful in preventing scarring in both congenital and secondary fibrotic atresias of the external auditory canal. These preliminary results are encouraging, and a prospective, placebo-controlled study appears to be warranted.


[Sociodemographic factors associated with symptoms of depression in a sample women held at two prisons in Mexico].
To determine the prevalence of depressive symptoms among a sample of women held in two Mexican prisons and to identify the sociodemographic factors associated with these symptoms. An exploratory, descriptive study was conducted of women 18-50 years of age in two prisons in the state of Veracruz, Mexico: the Pacho Viejo (PV) facility and Fortaleza San Carlos (FSC) facility. The Hamilton scale for depressive illness was applied and relationships were found between the participants' scores and their sociodemographic traits (age, marital status, number of children, jail work assignment, and number/frequency of visitors), legal status, type of crime committed, and length of sentence. The analysis employed Student's T test, Chi-squared test, and Student-Newman-Keuls' post hoc test, depending on the variable. All of the women studied at both facilities presented with symptoms of depression. Women at the PV facility had a lower score for depressive symptoms than those at FSC (20.8 +/- 0.8 versus 25.2 +/- 0.9; P <0.001). A higher score was found among women with children than among those without children (25.3 +/- 0.9 versus 21.8 +/- 1.3; P < 0.05); the group of women receiving weekly visits scored (15.0 +/- 1.3) significantly lower than the other groups (F[4.46] = 30.7; P < 0.0001). No significant differences were found to be related to marital status, work assignment, age, type of crime, or the length of sentence. Symptoms of depression were prevalent among the study sample, and were most powerfully related to having children and infrequent visits. Social adaptation programs should encourage continuous contact between women and their children, family, and friends.


Immunological detection of UV induced cyclobutane pyrimidine dimers and (6-4) photoproducts in DNA from reference bacteria and natural aquatic populations.
UV light-caused DNA damage is a widespread field of study. As UV light has the biological effect of inactivating or killing bacteria, it is used for water disinfection. Due to this application, it is important to study the DNA damage efficiencies and regeneration capacities in bacteria after UV irradiation. Two monoclonal antibodies, anti-CPD and anti-(6-4) PP, were applied for an immunoassay of UV-induced DNA modifications. Cyclobutane pyrimidine dimer (CPD) and 6-4 photoproduct (6-4 PP) were detected in the reference bacteria Pseudomonas aeruginosa and Enterococcus faecium, and in natural water communities. The antibody-mediated detection signals increased with the UV doses from 100-400J/m(2). Here, the CPD-specific signals were stronger than the (6-4) PP-specific signals. These immunological results were in accordance with parallel cultivation experiments. All UV-irradiated bacteria showed a reduction of their growth rate depending on UV application by several orders of magnitudes. The immunoassay was also applied to three types of natural aquatic habitats with different cell densities. Besides artificial UV irradiation, it was possible to visualize natural sunlight effects on these natural bacterial communities. Light-dependent and dark repair processes were distinguished using the established immunological assays. The antibody-mediated analyses presented are fast methods to detect UV-induced DNA lesions and repair capacities in selected bacterial species as well as in entire natural mixed populations.


A Comparative Evaluation of Animation and Small Multiples for Trend Visualization on Mobile Phones.
We compare the efficacy of animated and small multiples variants of scatterplots on mobile phones for comparing trends in multivariate datasets. Visualization is increasingly prevalent in mobile applications and mobile-first websites, yet there is little prior visualization research dedicated to small displays. In this paper, we build upon previous experimental research carried out on larger displays that assessed animated and non-animated variants of scatterplots. Incorporating similar experimental stimuli and tasks, we conducted an experiment where 96 crowdworker participants performed nine trend comparison tasks using their mobile phones. We found that those using a small multiples design consistently completed tasks in less time, albeit with slightly less confidence than those using an animated design. The accuracy results were more task-dependent, and we further interpret our results according to the characteristics of the individual tasks, with a specific focus on the trajectories of target and distractor data items in each task. We identify cases that appear to favor either animation or small multiples, providing new questions for further experimental research and implications for visualization design on mobile devices. Lastly, we provide a reflection on our evaluation methodology.


Disentangling the complexity of permafrost soil by using high resolution profiling of microbial community composition, key functions and respiration rates.
Thawing permafrost can stimulate microbial activity, leading to faster decomposition of formerly preserved organic matter and CO2 release. Detailed knowledge about the vertical distribution of the responsible microbial community that is changing with increasing soil depth is limited. In this study, we determined the microbial community composition from cores sampled in a high Arctic heath at Svalbard, Norway; spanning from the active layer (AL) into the permafrost layer (PL). A special aim has been on identifying a layer of recently thawed soil, the transition zone (TZ), which might provide new insights into the fate of thawing permafrost. A unique sampling strategy allowed us to observe a diverse and gradually shifting microbial community in the AL, a Bacteroidetes dominated community in the TZ and throughout the PL, a community strongly dominated by a single Actinobacteria family (Intrasporangiaceae). The contrasting abundances of these two taxa caused a community difference of about 60%, just within 3 cm from TZ to PL. We incubated subsamples at about 5°C and measured highest CO2 production rates under aerobic incubations, yet contrasting for five different layers and correlating to the microbial community composition. This high resolution strategy provides new insights on how microbial communities are structured in permafrost and a better understanding of how they respond to thaw.


Enrichment of Hard Sweeps on the X Chromosome in Drosophila melanogaster.
The characteristic properties of the X chromosome, such as male hemizygosity and its unique inheritance pattern, expose it to natural selection in a way that can be different from the autosomes. Here, we investigate the differences in the tempo and mode of adaptation on the X chromosome and autosomes in a population of Drosophila melanogaster. Specifically, we test the hypothesis that due to hemizygosity and a lower effective population size on the X, the relative proportion of hard sweeps, which are expected when adaptation is gradual, compared with soft sweeps, which are expected when adaptation is rapid, is greater on the X than on the autosomes. We quantify the incidence of hard versus soft sweeps in North American D. melanogaster population genomic data with haplotype homozygosity statistics and find an enrichment of the proportion of hard versus soft sweeps on the X chromosome compared with the autosomes, confirming predictions we make from simulations. Understanding these differences may enable a deeper understanding of how important phenotypes arise as well as the impact of fundamental evolutionary parameters on adaptation, such as dominance, sex-specific selection, and sex-biased demography.


How Research Evidence is Defined, Acquired, and Shared Across Systems That Address Intimate Partner Violence.
This exploratory study examined the flow of research evidence through systems that address intimate partner violence (IPV), including victim services, law enforcement, and criminal justice organizations. Qualitative interviews with representatives of these disciplines assessed how respondents define, acquire, and share research evidence. Findings suggest that research evidence is defined more broadly in the field than in academic settings, and is accessed primarily from trusted intermediaries within professional networks. State IPV coalitions and victim service providers are key intermediaries across sectors. Findings suggest the need for more tangible supports to support sharing of research information within and across service sectors.


Epidemiology of fungal keratitis in Queensland, Australia.
Fungal keratitis is a rare but sight-threatening ocular infection. The epidemiology varies with geography, in particular climate and demography. We present descriptive epidemiology of fungal keratitis in Queensland, a large, geographically heterogenous Australian state. Descriptive ecological study. Queensland residents in the period 1996 to January 2016. We searched the state-wide pathology database for positive fungal cultures from corneal scrapings, aqueous humour, vitreous humour or contact lens specimens. Data were analysed by age, sex, climate and location. Cumulative incidence rates were estimated. Episodes of fungal keratitis, from which the abovementioned positive fungal cultures were assumed to originate. Two hundred and twenty-one episodes of fungal keratitis in 215 Queensland residents were identified (140 males and 75 females). The median age was 48 years and the modal age range was 25-50 years. Seasonal variation was seen in tropical Queensland. Fusarium (33%) and Aspergillus (13%) were the commonest pathogens. The cumulative incidence per 100 000 population was 4.7, but was significantly higher in rural/regional (5.4) and tropical Queensland (7.9). In Queensland, fungal keratitis occurs most frequently in males under 50 with increased case identification associated with the hot dry season in tropical Queensland. The sex and age distribution may reflect increased environmental exposure to fungi related to occupation. The higher cumulative incidence in tropical Queensland is in keeping with the rates observed in other tropical regions of the world. Knowledge of the epidemiology of the condition is essential in formulating empirical antifungal regimens in suspected fungal keratitis.


Merging the departments of psychiatry of a private and state university: the Nebraska experience.
Medical colleges throughout the nation are being pressured to decrease the costs of medical education. In some of our smaller cities, the duplication of faculty expertise and costly technological resources at distinct but neighboring campuses has led to training costs far beyond what can be comfortably supported by either the institutions or their students. While the trend toward collaboration or mergers between identical medical departments on adjacent campuses is gaining ground, the methods required to achieve success in these ventures remain relatively uncharted. This paper provides an overview of the creation of successful merger between the departments of Psychiatry of Creighton University School of Medicine and the University of Nebraska College of Medicine. The development of the merger from conception to completion, along with the lessons learned along the way, are offered in the hope that other medical departments may benefit.