Three-dimensional dispersive metallic photonic crystals with a bandgap and a high cutoff frequency.
The goal of this work is to analyze three-dimensional dispersive metallic photonic crystals (PCs) and to find a structure that can provide a bandgap and a high cutoff frequency. The determination of the band structure of a PC with dispersive materials is an expensive nonlinear eigenvalue problem; in this work we propose a rational-polynomial method to convert such a nonlinear eigenvalue problem into a linear eigenvalue problem. The spectral element method is extended to rapidly calculate the band structure of three-dimensional PCs consisting of realistic dispersive materials modeled by Drude and Drude-Lorentz models. Exponential convergence is observed in the numerical experiments. Numerical results show that, at the low frequency limit, metallic materials are similar to a perfect electric conductor, where the simulation results tend to be the same as perfect electric conductor PCs. Band structures of the scaffold structure and semi-woodpile structure metallic PCs are investigated. It is found that band structures of semi-woodpile PCs have a very high cutoff frequency as well as a bandgap between the lowest two bands and the higher bands.


Are Categorical Spatial Relations Encoded by Shifting Visual Attention between Objects?
Perceiving not just values, but relations between values, is critical to human cognition. We tested the predictions of a proposed mechanism for processing categorical spatial relations between two objects-the shift account of relation processing-which states that relations such as 'above' or 'below' are extracted by shifting visual attention upward or downward in space. If so, then shifts of attention should improve the representation of spatial relations, compared to a control condition of identity memory. Participants viewed a pair of briefly flashed objects and were then tested on either the relative spatial relation or identity of one of those objects. Using eye tracking to reveal participants' voluntary shifts of attention over time, we found that when initial fixation was on neither object, relational memory showed an absolute advantage for the object following an attention shift, while identity memory showed no advantage for either object. This result is consistent with the shift account of relation processing. When initial fixation began on one of the objects, identity memory strongly benefited this fixated object, while relational memory only showed a relative benefit for objects following an attention shift. This result is also consistent, although not as uniquely, with the shift account of relation processing. Taken together, we suggest that the attention shift account provides a mechanistic explanation for the overall results. This account can potentially serve as the common mechanism underlying both linguistic and perceptual representations of spatial relations.


Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival.
Tooth loss for 100 treated periodontal patients (2,509 teeth) under maintenance care was evaluated to determine the effectiveness of commonly taught clinical parameters utilized in the assignment of prognosis in accurately predicting tooth survival. Previous studies in this series evaluated prognosis as a surrogate variable representing the condition of the tooth at a particular point. In this study, survival analysis was used to evaluate the relationship of these common clinical parameters to an actual end point, tooth loss. Robust log rank tests indicated that initial probing depth, initial furcation involvement, initial mobility, initial crown-to-root ratio, and initial root form were all associated with tooth loss. In addition, smoking and increased initial bone loss were both found to be associated with increased risk of tooth loss while fixed abutment status was associated with a decreased risk of tooth loss. A Cox proportional hazards regression model showed that initial probing depth, initial furcation involvement, initial mobility, initial percent bone loss, presence of a parafunctional habit without a biteguard, and smoking were all associated with an increased risk of tooth loss. This model suggests that patients are twice as likely to loose their teeth if there is increasing mobility, if they have a parafunctional habit and do not wear a biteguard, or if they smoke. From these data there does appear to be a relationship between the assigned prognosis and tooth loss. Teeth with worse prognosis have a worse survival rate, but the commonly taught clinical parameters used in the traditional method of assignment of prognosis do not adequately explain that relationship. Furthermore, initial prognosis did not adequately explain the condition of the tooth or accurately predict the tooth's survival. These results seem to indicate that the effect of these clinical parameters on tooth survival is only partially reflected in the assigned prognosis initially, suggesting that perhaps some of the clinical parameters should be weighed more heavily than others when assigning prognosis. Further studies are needed to develop a more accurate method for the assignment of prognosis.


Emotion recognition and cognitive empathy deficits in adolescent offenders revealed by context-sensitive tasks.
Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs) but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI) and executive functions (EFs) in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables.


Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.
Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults. In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years). Studies limited to patients with chronic respiratory diseases or psychiatric disease, patients on extracorporeal life support, or patients treated with hyperbaric oxygen therapy or elective surgery were excluded. We screened studies and extracted summary estimates independently and in duplicate. We also extracted individual patient-level data from survival curves. The main outcomes were mortality (in-hospital, at 30 days, and at longest follow-up) and morbidity (disability at longest follow-up, risk of hospital-acquired pneumonia, any hospital-acquired infection, and length of hospital stay) assessed by random-effects meta-analyses. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation approach. This study is registered with PROSPERO, number CRD42017065697. 25 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery. Compared with a conservative oxygen strategy, a liberal oxygen strategy (median baseline saturation of peripheral oxygen [SpO2] across trials, 96% [range 94-99%, IQR 96-98]) increased mortality in-hospital (relative risk [RR] 1·21, 95% CI 1·03-1·43, I2=0%, high quality), at 30 days (RR 1·14, 95% CI 1·01-1·29, I2=0%, high quality), and at longest follow-up (RR 1·10, 95% CI 1·00-1·20, I2=0%, high quality). Morbidity outcomes were similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses. In acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. Supplemental oxygen might become unfavourable above an SpO2 range of 94-96%. These results support the conservative administration of oxygen therapy. None.


Genome diversification in phylogenetic lineages I and II of Listeria monocytogenes: identification of segments unique to lineage II populations.
Thirteen different serotypes of Listeria monocytogenes can be distinguished on the basis of variation in somatic and flagellar antigens. Although the known virulence genes are present in all serotypes, greater than 90% of human cases of listeriosis are caused by serotypes 1/2a, 1/2b, and 4b and nearly all outbreaks of food-borne listeriosis have been caused by serotype 4b strains. Phylogenetic analysis of these three common clinical serotypes places them into two different lineages, with serotypes 1/2b and 4b belonging to lineage I and 1/2a belonging to lineage II. To begin examining evolution of the genome in these serotypes, DNA microarray analysis was used to identify lineage-specific and serotype-specific differences in genome content. A set of 44 strains representing serotypes 1/2a, 1/2b, and 4b was probed with a shotgun DNA microarray constructed from the serotype 1/2a strain 10403s. Clones spanning 47 different genes in 16 different contiguous segments relative to the lineage II 1/2a genome were found to be absent in all lineage I strains tested (serotype 4b and 1/2b) and an additional nine were altered exclusively in 4b strains. Southern hybridization confirmed that conserved alterations were, in all but two loci, due to absence of the segments from the genome. Genes within these contiguous segments comprise five functional categories, including genes involved in synthesis of cell surface molecules and regulation of virulence gene expression. Phylogenetic reconstruction and examination of compositional bias in the regions of difference are consistent with a model in which the ancestor of the two lineages had the 1/2 somatic serotype and the regions absent in the lineage I genome arose by loss of ancestral sequences.


Interferometric measurement of visual acuity and the effect of ocular chromatic aberration.
Ocular chromatic aberration is expected on theoretical grounds to affect the quality of polychromatic interference fringes generated on the retina if the interferometer is not perfectly centered on the eye's visual axis. Of primary concern is a loss of contrast resulting from wavelength-dependent phase shifts of the fringes. By using an interferometer with just two wavelengths of light, we demonstrated this phase shift directly and measured its magnitude as a function of interferometer displacement. Then, using white-light fringes we measured visual acuity and found a threefold loss of acuity when the light from the interferometer entered the eye near the margin of the pupil. These results are consistent with predictions based on a simple optical model of ocular chromatic aberration.


Physician assistants in Texas.
Understanding the health requirements of a state begins with identifying the population at need and the workforce available to meet those needs. A descriptive study was undertaken to examine the physician assistant (PA) workforce in Texas as part of an ongoing effort to meet the health needs of Texas residents. In September 2000, Texas had 2237 licensed PAs practicing in 186 counties. Education for PAs in Texas began in 1970 and currently includes one private, one military, and six public programs. Most practicing PAs in Texas graduate from in-state programs and tend to locate within the state. Preparations are under way to shift the public undergraduate programs to graduate degree programs. Although barriers to health care access in Texas remain a substantial public health issue, PAs have helped reduce these barriers, especially in many rural communities. The supply of and demand for Texas PAs appear to be in equilibrium. Policy implications are discussed.


Vegetarian dietary patterns and mortality in Adventist Health Study 2.
Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. To evaluate the association between vegetarian dietary patterns and mortality. Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Adventist Health Study 2 (AHS-2), a large North American cohort. A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.


Clinical trials and approval of anti-cancer agents.
Nowadays, drug development requires large-scale studies to show the real clinical benefit for the patients, which means recruiting a sufficient number of patients, even internationally. As global studies enable simultaneous delivery of new drugs and sharing of safety information around the world, multinational studies now account for around 20% of Japanese clinical studies. Until recently, drug development has been centered in Western countries, but interest in Asian regions has increased. In this environment, one important factor in drug development is ethnicity. Various cancers show regional patterns in their incidence, and some (such as liver cancer and gastric cancer) show high incidences in Asian countries. Ethnic factors including genetic differences, such as the CYP drug-metabolizing enzymes in the liver and gene mutations, may result in different drug responses in terms of efficacy and safety. Examples of ethnic differences in drug responses were seen with gefitinib, which showed a different efficacy data, and with sunitinib, showing a clearly different toxicity profile between the West and Asia. Therefore, ethnic differences need to be taken into account in the early phase of drug development, and Asian countries need to be involved early in clinical development. Asian collaboration among physicians and networks of specialists is also important, and there is good potential for successful establishment of the infrastructure needed for collaborative clinical trials. Establishment of a so-called third development center in Asian countries that will complement the USA and European centers is highly desired.


Assessment of the chemical quality of drinking water in Cambodia.
Most water supply programmes in Cambodia have focused on providing access to bacteriologically safe water, an approach which has led to an increasing reliance on ground water, especially in rural areas. However, there have been very few data collected on the chemical quality of the nation's drinking water sources, and few water supply programmes have the capacity to assess chemical quality. The study was designed to address this data gap by conducting a low-cost, rapid assessment of drinking water sources nationwide to determine whether there were any chemicals of concern in Cambodian water supply sources. Results of the assessment confirm that there are several parameters of health and aesthetic concern; dissolved arsenic is the most significant. Elevated arsenic levels (some exceeding 500 microgl(-1)) were detected in aquifers of moderate depth in several highly populated areas, confirming that further investigation of the occurrence of arsenic contamination in Cambodia is warranted. Other chemicals of health concern include nitrate, nitrite, fluoride and manganese. Additionally, many ground water sources are negatively impacted by parameters of aesthetic concern, such as iron, manganese, hardness and total dissolved solids. Elevated levels of these parameters have caused consumers to reject newly installed water supplies, often in favour of surface water sources that are bacteriologically unsafe.


The DEXLIFE study methods: identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals.
The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.


Capsule endoscopy for the diagnosis and follow up of Crohn's disease: a comprehensive review of current status.
Capsule endoscopy (CE) has revolutionized the diagnosis and monitoring of small bowel Crohn's disease (CD). The procedure is patient friendly and noninvasive, and compared to cross-sectional imaging, CE allows a direct and detailed evaluation of the entire small bowel mucosa with a high sensitivity for the earliest lesions of CD. Today, CE is the leading modality for visualizing the small bowel in suspected CD, and validated activity indices are available for the follow up of patients with established CD. CE of the entire gastrointestinal tract (panenteric CE) was recently introduced as a new diagnostic approach in patients examined for CD, and preliminary results are promising. There are important limitations, involving mainly capsule retention. Furthermore, a diagnostic criterion for CD has never been validated, and lesions detected by CE are not specific for CD. Hence, concern has been raised about a low specificity compared to other diagnostic modalities. Important questions about the optimal bowel preparation, selection of patients for CE and the optimal reading protocol remain to be clarified. The aim of this review is to evaluate the performance of CE for diagnosing CD and assess disease activity in known CD; to compare the diagnostic accuracy of CE to that of cross-sectional imaging; to discuss limitations; and to define the place of CE in the diagnostic algorithm in suspected or known CD.


Human genetic differentiation across the Strait of Gibraltar.
The Strait of Gibraltar is a crucial area in the settlement history of modern humans because it represents a possible connection between Africa and Europe. So far, genetic data were inconclusive about the fact that this strait constitutes a barrier to gene flow, as previous results were highly variable depending on the genetic locus studied. The present study evaluates the impact of the Gibraltar region in reducing gene flow between populations from North-Western Africa and South-Western Europe, by comparing formally various genetic loci. First, we compute several statistics of population differentiation. Then, we use an original simulation approach in order to infer the most probable evolutionary scenario for the settlement of the area, taking into account the effects of both demography and natural selection at some loci. We show that the genetic patterns observed today in the region of the Strait of Gibraltar may reflect an ancient population genetic structure which has not been completely erased by more recent events such as Neolithic migrations. Moreover, the differences observed among the loci (i.e. a strong genetic boundary revealed by the Y-chromosome polymorphism and, at the other extreme, no genetic differentiation revealed by HLA-DRB1 variation) across the strait suggest specific evolutionary histories like sex-mediated migration and natural selection. By considering a model of balancing selection for HLA-DRB1, we here estimate a coefficient of selection of 2.2% for this locus (although weaker in Europe than in Africa), which is in line with what was estimated from synonymous versus non-synonymous substitution rates. Selection at this marker thus appears strong enough to leave a signature not only at the DNA level, but also at the population level where drift and migration processes were certainly relevant. Our multi-loci approach using both descriptive analyses and Bayesian inferences lead to better characterize the role of the Strait of Gibraltar in the evolution of modern humans. We show that gene flow across the Strait of Gibraltar occurred at relatively high rates since pre-Neolithic times and that natural selection and sex-bias migrations distorted the demographic signal at some specific loci of our genome.


Heart beat classification from single-lead ECG using the synchrosqueezing transform.
The processing of ECG signal provides a wealth of information on cardiac function and overall cardiovascular health. While multi-lead ECG recordings are often necessary for a proper assessment of cardiac rhythms, they are not always available or practical, for example in fetal ECG applications. Moreover, a wide range of small non-obtrusive single-lead ECG ambulatory monitoring devices are now available, from which heart rate variability (HRV) and other health-related metrics are derived. Proper beat detection and classification of abnormal rhythms is important for reliable HRV assessment and can be challenging in single-lead ECG monitoring devices. In this manuscript, we modelled the heart rate signal as an adaptive non-harmonic model and used the newly developed synchrosqueezing transform (SST) to characterize ECG patterns. We show how the proposed model can be used to enhance heart beat detection and classification between normal and abnormal rhythms. In particular, using the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database and the Association for the Advancement of Medical Instrumentation (AAMI) beat classes, we trained and validated a support vector machine (SVM) classifier on a portion of the annotated beat database using the SST-derived instantaneous phase, the R-peak amplitudes and R-peak to R-peak interval durations, based on a single ECG lead. We obtained sentivities and positive predictive values comparable to other published algorithms using multiple leads and many more features.


Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans.
This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. Single-cell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT(1)), and western blotting was used to determine AT(1) protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT(1). These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels. Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). These data demonstrate that the AT(1) is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.


BCG-malaria co-Infection has paradoxical effects on C57BL/6 and A/J mouse strains.
Bacillus Calmette-Guérin (BCG) infection of the spleen is a potent modifier of splenic function. Prior to malaria infection, we infected two mouse strains of differing susceptibility to Plasmodium chabaudi AS (C57BL/6 and A/J) with this mycobacterium. We then evaluated aspects of spleen cell composition, architecture and cytokine expression, and correlated these with the outcome. BCG preinfection resulted in protection of the A/J mice but paradoxically resulted in mortality of the C57BL/6 mice. The latter developed higher parasitaemias that peaked earlier than the A/J mice rendered resistant by BCG. BCG infection induced remarkable changes to splenic histology examined by H&E staining, but there were no consistent differences between mouse strains. C57BL/6 mice had higher absolute numbers of all immune cell phenotypes than did A/J mice, and higher macrophage and dendritic cell proportions. BCG-induced resistance in A/J mice was associated with an increased CD4+ expression of IFN-gamma whilst induced death in C57BL/6 mice was associated with excessive IFN-gamma expression. A moderate TH1 response in the A/J model may have been responsible for the improved survival, and an excessive TH1 response in the C57BL/6 model may have contributed to their death.


A genome-wide association study of hypertension and blood pressure in African Americans.
The evidence for the existence of genetic susceptibility variants for the common form of hypertension ("essential hypertension") remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8 x 10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1 x 10(-7)). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments.


Dioxin levels in fertilizers from Belgium: determination and evaluation of the potential impact on soil contamination.
Dioxins are harmful persistent organic pollutants (POPs) to which humans are exposed mostly via the consumption of animal products. They can enter the food chain at any stage, including crop fertilization. Fertilizers belong to several categories: synthetic chemicals providing the essential elements (mostly N, P and K) that are required by the crops but also organic fertilizers or amendments, liming materials, etc. Ninety-seven samples of fertilizers were taken in Belgium during the year 2011 and analyzed after a soft extraction procedure for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) using GC-IDHRMS. Only small qualitative differences could be observed between the main fertilizer categories since the PCDD:PCDF:DL-PCB average ratio obtained with the results expressed in TEQ was often close to 30:30:40 (typically for sewage sludge) or 40:30:30 (typically for compost). The median dioxin levels determined were generally lower than recorded previously and were the highest for sewage sludge and compost (5.6 and 5.5 ng TEQ/kg dry weight (dw), respectively). The levels in other fertilizers were lower including manure for which the median value was only 0.2 ng TEQ/kg dw. Several fertilization scenarios relying on the use of those fertilizers were assessed taking into consideration the application conditions prevailing in Belgium. From this assessment it could be concluded that the contribution of fertilizers to the overall soil contamination will be low by comparison of other sources of contamination such as atmospheric depositions. At the field scale, intensive use of compost and sewage sludge will increase dramatically the dioxin inputs compared with other fertilization practices but this kind of emission to the soil will still be relatively low compared to the dioxin atmospheric depositions.


Bridging the childhood epilepsy treatment gap in northern Nigeria (BRIDGE): Rationale and design of pre-clinical trial studies.
Epilepsy is the most common serious childhood neurological disorder. In the low- and middle-income countries (LMICs) of Africa, children with epilepsy suffer increased morbidity and mortality compared to their counterparts in high-income countries, and the majority do not receive treatment - the childhood epilepsy treatment gap. Reports of the childhood epilepsy treatment gap in Africa are likely underestimates; most surveys do not include several common childhood seizure types, including most types of non-convulsive epilepsy. Efforts to scale up childhood epilepsy care services in the LMICs of Africa must contend with a shortage of physicians and diagnostic technology [e.g., electroencephalograms (EEGs)]. One pragmatic solution is to integrate epilepsy care into primary care by task-shifting to community health extension workers. The aims of this project (BRIDGE) are to: 1) train, develop, and pilot task-shifted epilepsy care teams; 2) develop and pilot innovative childhood epilepsy screening and diagnostic paradigms adapted to the local Hausa language/culture in Kano, northern Nigeria; and, 3) quantify and map the childhood epilepsy treatment gap, using geographic information systems (GIS), to target limited resources to areas of greatest need. Task-shifted teams will diagnose and manage childhood epilepsy using an innovative epilepsy screening tools and diagnostic and management paradigms in environments with limited EEG access. If validated and demonstrated efficacious in clinical trials, this project can be taken to scale across broader areas of west Africa's LMICs that share language and culture. BRIDGE has the potential to enhance access to basic childhood epilepsy care and establish the foundation for childhood epilepsy clinical trials in west Africa.


Differential combinatorial coding of pheromones in two olfactory subsystems of the honey bee brain.
Neural coding of pheromones has been intensively studied in insects with a particular focus on sex pheromones. These studies favored the view that pheromone compounds are processed within specific antennal lobe glomeruli following a specialized labeled-line system. However, pheromones play crucial roles in an insect's life beyond sexual attraction, and some species use many different pheromones making such a labeled-line organization unrealistic. A combinatorial coding scheme, in which each component activates a set of broadly tuned units, appears more adapted in this case. However, this idea has not been tested thoroughly. We focused here on the honey bee Apis mellifera, a social insect that relies on a wide range of pheromones to ensure colony cohesion. Interestingly, the honey bee olfactory system harbors two central parallel pathways, whose functions remain largely unknown. Using optophysiological recordings of projection neurons, we compared the responses of these two pathways to 27 known honey bee pheromonal compounds emitted by the brood, the workers, and the queen. We show that while queen mandibular pheromone is processed by l-ALT (lateral antennal lobe tract) neurons and brood pheromone is mainly processed by m-ALT (median antennal lobe tract) neurons, worker pheromones induce redundant activity in both pathways. Moreover, all tested pheromonal compounds induce combinatorial activity from several AL glomeruli. These findings support the combinatorial coding scheme and suggest that higher-order brain centers reading out these combinatorial activity patterns may eventually classify olfactory signals according to their biological meaning.


Effects of optical feedback in a birefringence-Zeeman dual frequency laser at high optical feedback levels.
Optical feedback effects are studied in a birefringence-Zeeman dual frequency laser at high optical feedback levels. The intensity modulation features of the two orthogonally polarized lights are investigated in both isotropic optical feedback (IOF) and polarized optical feedback (POF). In IOF, the intensities of both beams are modulated simultaneously, and four zones, i.e., the e-light zone, the o-light and e-light zone, the o-light zone, and the no-light zone, are formed in a period corresponding to a half laser wavelength displacement of the feedback mirror. In POF, the two orthogonally polarized lights will oscillate alternately. Strong mode competition can be observed, and it affects the phase difference between the two beams greatly. The theoretical analysis is presented, which is in good agreement with the experimental results. The potential use of the experimental results is also discussed.


Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number.
Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum-in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues-incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.


Postnatal weight and height growth modeling and prediction of body mass index as a function of time for the study of growth determinants.
Weight, height and body mass index (BMI) growth trajectories have been associated with several chronic diseases in later life. Our aim was to describe a method to model individual weight and height growth curves during infancy and to show how it can be used to study their determinants and relationships with later health outcomes as well as to predict BMI trajectories. In the EDEN mother-child cohort, we collected 17 measurements of weight and 16 of length/height per child between birth and 3 years of age in 1,900 infants from their health care booklet and during the study clinical examinations at 1 and 3 years; 1,436 (76%) had at least 1 measurement between 2 and 3 years. We fitted individual weight and height growth trajectories using the Jenss nonlinear model including random effects using the 'SAEMIX' package (R software). We studied whether individual growth model parameters were associated with gender in one- and two-step approaches. We indirectly calculated BMI increase against time from both weight and height growth models combined and compared the fit with a direct multilevel spline model. By modeling observed growth data, we homogenized the data in terms of number and age of measurements and were able to calculate other specific parameters as growth velocities.


Photic injury to cultured RPE varies among individual cells in proportion to their endogenous lipofuscin content as modulated by their melanosome content.
We determined whether photic stress differentially impairs organelle motility of RPE lipofuscin and melanin granules, whether lethal photic stress kills cells in proportion to lipofuscin abundance, and whether killing is modulated by melanosome content. Motility of endogenous lipofuscin and melanosome granules within the same human RPE cells in primary culture was quantified by real-time imaging during sublethal blue light irradiation. Cell death during lethal irradiation was quantified by dynamic imaging of the onset of nuclear propidium iodide fluorescence. Analyzed were individual cells containing different amounts of autofluorescent lipofuscin, or similar amounts of lipofuscin and a varying content of phagocytized porcine melanosomes, or phagocytized black latex beads (control for light absorbance). Lipofuscin granules and melanosomes showed motility slowing with mild irradiation, but slowing was greater for lipofuscin. On lethal irradiation, cell death was earlier in cells with higher lipofuscin content, but delayed by the copresence of melanosomes. Delayed death did not occur with black beads, suggesting that melanosome protection was due to properties of the biological granule, not simple screening. Greater organelle motility slowing of the more photoreactive lipofuscin granule compared to melanosomes suggests that lipofuscin mediates mild photic injury within RPE cells. With lethal light stress endogenous lipofuscin mediates killing, but the effect is cell autonomous and modulated by coincident melanosome content. Developing methods to quantify the frequency of individual cells with combined high lipofuscin and low melanosome content may have value for predicting the photic stress susceptibility of the RPE monolayer in situ.


Three-dimensional microstructural imaging methods for energy materials.
Advances in the design of materials for energy storage and conversion (i.e., "energy materials") increasingly rely on understanding the dependence of a material's performance and longevity on three-dimensional characteristics of its microstructure. Three-dimensional imaging techniques permit the direct measurement of microstructural properties that significantly influence material function and durability, such as interface area, tortuosity, triple phase boundary length and local curvature. Furthermore, digital representations of imaged microstructures offer realistic domains for modeling. This article reviews state-of-the-art methods, across a spectrum of length scales ranging from atomic to micron, for three-dimensional microstructural imaging of energy materials. The review concludes with an assessment of the continuing role of three-dimensional imaging in the development of novel materials for energy applications.


Nutrition therapy for liver diseases based on the status of nutritional intake.
The dietary intake of patients with nonalcoholic fatty liver disease (NAFLD) is generally characterized by high levels of carbohydrate, fat, and/or cholesterol, and these dietary patterns influence hepatic lipid metabolism in the patients. Therefore, careful investigation of dietary habits could lead to better nutrition therapy in NAFLD patients. The main treatment for chronic hepatitis C (CHC) is interferon-based antiviral therapy, which often causes a decrease in appetite and energy intake; hence, nutritional support is also required during therapy to prevent undernourishment, treatment interruption, and a reduction in quality of life. Moreover, addition of some nutrients that act to suppress viral proliferation is recommended. As a substitutive treatment, low-iron diet therapy, which is relatively safe and effective for preventing hepatocellular carcinoma, is also recommended for CHC patients. Some patients with liver cirrhosis (LC) have decreased dietary energy and protein intake, while the number of LC patients with overeating and obesity is increasing, indicating that the nutritional state of LC patients has a broad spectrum. Therefore, nutrition therapy for LC patients should be planned on an assessment of their complications, nutritional state, and dietary intake. Late evening snacks, branched-chain amino acids, zinc, and probiotics are considered for effective nutritional utilization.


Strategies for reducing potentially avoidable hospitalizations for ambulatory care-sensitive conditions.
Hospitalizations for ambulatory care-sensitive conditions (ACSCs) are seen as potentially avoidable with optimal primary care. Little is known, however, about how primary care physicians rate these hospitalizations and whether and how they could be avoided. This study explores the complex causality of such hospitalizations from the perspective of primary care physicians. We conducted semistructured interviews with 12 primary care physicians from 10 primary care clinics in Germany regarding 104 hospitalizations of 81 patients with ACSCs at high risk of rehospitalization. Participating physicians rated 43 (41%) of the 104 hospitalizations to be potentially avoidable. During the interviews the cause of hospitalization fell into 5 principal categories: system related (eg, unavailability of ambulatory services), physician related (eg, suboptimal monitoring), medical (eg, medication side effects), patient related (eg, delayed help-seeking), and social (eg, lack of social support). Subcategories frequently associated with physicians' rating of hospitalizations for ACSCs as potentially avoidable were after-hours absence of the treating physician, failure to use ambulatory services, suboptimal monitoring, patients' fearfulness, cultural background and insufficient language skills of patients, medication errors, medication nonadherence, and overprotective caregivers. Comorbidities and medical emergencies were frequent causes attributed to ACSC-based hospitalizations that were rated as being unavoidable. Primary care physicians rated a significant proportion of hospitalizations for ACSCs to be potentially avoidable. Strategies to avoid these hospitalizations may target after-hours care, optimal use of ambulatory services, intensified monitoring of high-risk patients, and initiatives to improve patients' willingness and ability to seek timely help, as well as patients' medication adherence.


Transurethral electrovapor resection versus standard transurethral resection treatment for a large prostate: a 2-year follow-up study conducted in Taiwan.
Those patients featuring a large prostate and undergoing transurethral resection typically face a longer duration of surgery, they have a higher degree of hemorrhage and a higher irrigant volume required for the procedure, and they tend to reflect a higher incidence of morbidity than is the case for a small prostate. We report on the relative safety and efficacy of transurethral electrovapor resection of the prostate (TUVRP) as compared with standard transurethral resection of the prostate (TURP) for Taiwanese patients having a prostate size >50 ml. Seventy-six symptomatic benign prostatic hyperplasia patients featuring a prostate size >50 ml were randomized and underwent either TUVRP using wedge loop or standard TURP. Perioperative parameters, treatment outcome, and adverse events associated with the surgical procedure are assessed herein. Mean operation time, changes in hemoglobin levels, resected prostate weight, perioperative irrigant volume needed, and incidences of recatheterizations and readmissions, all differed significantly when the two surgical procedures were compared. The average expense differences for the two procedures were impressive (p < 0.0001). No postoperative intergroup sexual dysfunction differences were noted. Clinical improvements following either TUVRP or TURP were significant and sustained for at least a period of 2 years. Intergroup comparison of International Prostate Symptom Score, quality of life, peak flow rate, and postvoid residual volume revealed no significant differences at 2 years (p = 0.45, 0.48, 0.12, and 0.29, respectively). The need for postoperative medical retreatment and/or reoperation did not differ significantly between the two groups (p = 0.62 and p = 0.56, respectively, at 6 months and p = 0.47 and p = 0.48, respectively, at 2 years). The TUVRP procedure offers advantages as regards a number of perioperative parameters when compared with the TURP procedure, and it seems that TUVRP might provide at least an equivalent treatment outcome as is the case for TURP.


The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.
Murine studies have shown that apolipoprotein E modulates pulmonary function during development, aging, and allergen-induced airway disease. It is not known whether the polymorphic human APOE gene influences pulmonary function. We assessed whether an association exists between the polymorphic human APOE ε2, ε3, and ε4 alleles and pulmonary function among participants in the Long Life Family Study. Data from 4,468 Caucasian subjects who had genotyping performed for the APOE ε2, ε3, and ε4 alleles were analyzed, with and without stratification by sex. Statistical models were fitted considering the effects of the ε2 allele, defined as ε2/2 or ε2/3 genotypes, and the ε4 allele, defined as ε3/4 or ε4/4 genotypes, which were compared to the ε3/3 genotype. The mean FEV1/FVC ratio (the forced expiratory volume in one second divided by the forced vital capacity) was lower among women with the ε4 allele as compared to women with the ε3/3 genotype or the ε2 allele. Carriage of the APOE ε4 allele was associated with FEV1/FVC, which implied lower values. Further analysis showed that the association primarily reflected women without lung disease who were older than 70 years. The association was not mediated by lipid levels, smoking status, body mass index, or cardiovascular disease. This study for the first time identifies that the APOE gene is associated with modified lung physiology in women. This suggests that a link may exist between the APOE ε4 allele, female sex, and a reduction in the FEV1/FVC ratio in older individuals.


Enhancing emotional experiences to dance through music: the role of valence and arousal in the cross-modal bias.
It is well established that emotional responses to stimuli presented to one perceptive modality (e.g., visual) are modulated by the concurrent presentation of affective information to another modality (e.g., auditory)-an effect known as the cross-modal bias. However, the affective mechanisms mediating this effect are still not fully understood. It remains unclear what role different dimensions of stimulus valence and arousal play in mediating the effect, and to what extent cross-modal influences impact not only our perception and conscious affective experiences, but also our psychophysiological emotional response. We addressed these issues by measuring participants' subjective emotion ratings and their Galvanic Skin Responses (GSR) in a cross-modal affect perception paradigm employing videos of ballet dance movements and instrumental classical music as the stimuli. We chose these stimuli to explore the cross-modal bias in a context of stimuli (ballet dance movements) that most participants would have relatively little prior experience with. Results showed (i) that the cross-modal bias was more pronounced for sad than for happy movements, whereas it was equivalent when contrasting high vs. low arousal movements; and (ii) that movement valence did not modulate participants' GSR, while movement arousal did, such that GSR was potentiated in the case of low arousal movements with sad music and when high arousal movements were paired with happy music. Results are discussed in the context of the affective dimension of neuroentrainment and with regards to implications for the art community.


Bridging all oral DAA therapy from wait time to post-liver transplant to improve HCV eradication?
Recurrence of hepatitis C is a major cause of graft loss and shortened survival in patients receiving a liver transplant (LT) for end-stage hepatitis C virus (HCV) infection. The only way to improve graft and patient outcomes is a successful eradication of HCV infection by antiviral therapy either before or after transplant. This was achievable in a small proportion of recipients by IFN-based regimens, but could be obtained in the majority of them by using DAA IFN-free regimens before/after transplant. We describe a patient with decompensated cirrhosis because of severe recurrent hepatitis C, who had a retransplant following treatment with a combination of sofosbuvir and riba virin that started during the waiting time and was carried over during both the transplant and post-transplant phases for an overall period of 24 weeks. The patient gave a written consent to receive Sofosbuvir plus Rbv therapy pre and post-transplant. Post-transplant serum HCV-RNA remains undetectable 24 weeks after discontinuing sofosbuvir and ribavirin (SVR24). Waiting for direct antiviral agents combinations, our findings not only support the use of sofosbuvir plus ribavirin as the first-line treatment in all patients on the LT waiting list, but also suggest to bridge treatment to the post-transplant period in case HCV RNA undetectability for at least 30 days has not been achieved at the time of LT.


Vibrational Sum Frequency Spectroscopy on Polyelectrolyte Multilayers: Effect of Molecular Surface Structure on Macroscopic Wetting Properties.
Adsorption of a single layer of molecules on a surface, or even a reorientation of already present molecules, can significantly affect the surface properties of a material. In this study, vibrational sum frequency spectroscopy (VSFS) has been used to study the change in molecular structure at the solid-air interface following thermal curing of polyelectrolyte multilayers of poly(allylamine hydrochloride) and poly(acrylic acid). Significant changes in the VSF spectra were observed after curing. These changes were accompanied by a distinct increase in the static water contact angle, showing how the properties of the layer-by-layer molecular structure are controlled not just by the polyelectrolyte in the outermost layer but ultimately by the orientation of the chemical constituents in the outermost layers.


Re-mapping the molecular features of the human immunodeficiency virus type 1 and human T-cell lymphotropic virus type 1 Brazilian sequences using a bioinformatics unit established in Salvador, Bahia, Brazil, to give support to the viral epidemiology studies.
The analysis of genetic data for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1) is essential to improve treatment and public health strategies as well as to select strains for vaccine programs. However, the analysis of large quantities of genetic data requires collaborative efforts in bioinformatics, computer biology, molecular biology, evolution, and medical science. The objective of this study was to review and improve the molecular epidemiology of HIV-1 and HTLV-1 viruses isolated in Brazil using bioinformatic tools available in the Laboratório Avançado de Sáude Pública (Lasp) bioinformatics unit. The analysis of HIV-1 isolates confirmed a heterogeneous distribution of the viral genotypes circulating in the country. The Brazilian HIV-1 epidemic is characterized by the presence of multiple subtypes (B, F1, C) and B/F1 recombinant virus while, on the other hand, most of the HTLV-1 sequences were classified as Transcontinental subgroup of the Cosmopolitan subtype. Despite the high variation among HIV-1 subtypes, protein glycosylation and phosphorylation domains were conserved in the pol, gag, and env genes of the Brazilian HIV-1 strains suggesting constraints in the HIV-1 evolution process. As expected, the functional protein sites were highly conservative in the HTLV-1 env gene sequences. Furthermore, the presence of these functional sites in HIV-1 and HTLV-1 strains could help in the development of vaccines that pre-empt the viral escape process.


Role of input self-sufficiency in the economic and environmental sustainability of specialised dairy farms.
Increasing input self-sufficiency is often viewed as a target to improve sustainability of dairy farms. However, few studies have specifically analysed input self-sufficiency, by including several technical inputs and without only focussing on animal feeding, in order to explore its impact on farm sustainability. To address this gap, our work has three objectives as follows: (1) identifying the structural characteristics required by specialised dairy farms located in the grassland area to be self-sufficient; (2) analysing the relationships between input self-sufficiency, environmental and economic sustainability; and (3) studying how the farms react to a decrease in milk price according to their self-sufficiency degree. Based on farm accounting databases, we categorised 335 Walloon specialised conventional dairy farms into four classes according to their level of input self-sufficiency. To this end, we used as proxy the indicator of economic autonomy - that is, the ratio between costs of inputs related to animal production, crop production and energy use and the total gross product. Classes were then compared using multiple comparison tests and canonical discriminant analysis. A total of 30 organic farms - among which 63% had a high level of economic autonomy - were considered separately and compared with the most autonomous class. We showed that a high degree of economic autonomy is associated, in conventional farms, with a high proportion of permanent grassland in the agricultural area. The most autonomous farms used less input - especially animal feeding - for a same output level, and therefore combined good environmental and economic performances. Our results also underlined that, in a situation of decrease in milk price, the least autonomous farms had more latitude to decrease their input-related costs without decreasing milk production. Their incomes per work unit were, therefore, less impacted by falling prices, but remained lower than those of more autonomous farms. In such a situation, organic farms kept stable incomes, because of a slighter decrease in organic milk price. Our results pave the way to study the role of increasing input self-sufficiency in the transition of dairy farming systems towards sustainability. Further research is required to study a wide range of systems and agro-ecological contexts, as well as to consider the evolution of farm sustainability in the long term.


The beta-human chorionic gonadotropin-related peptide LQGV exerts anti-inflammatory effects through activation of the adrenal gland and glucocorticoid receptor in C57BL/6 mice.
The systemic inflammatory response syndrome is a complex host response to a variety of clinical insults, generally leading to severe pathology. The human chorionic gonadotropin β-chain-related tetrapeptide leucine-glutamine-glycine-valine (LQGV) reduces hemorrhagic and LPS-induced systemic inflammatory response syndrome, but its mechanisms of action are not yet fully understood. Through the combination of in vivo, in vitro, and ex vivo approaches, we demonstrate that LQGV actively stimulates corticosterone production in mice and thereby suppresses in vivo TLR4-directed inflammation upon LPS administration. Blocking in vivo glucocorticosteroid receptor signaling reduced the prosurvival effect of LQGV. Also, upon multiple TLR activation by heat-killed Listeria monocytogenes, splenocytes from LQGV-treated mice produced significantly less TNF-α and IL-6, which was absent after in vitro blockage of the glucocorticosteroid receptor. Using adrenal gland and adrenal cell line cultures, we show that LQGV stimulates corticosterone production. Moreover, by using specific pharmacological inhibitors of the adrenocorticotropic hormone (ACTH) and luteinizing hormone receptors as well as of cAMP signaling, we demonstrate that LQGV stimulates the ACTH receptor. These data show that the β-human chorionic gonadotropin-related tetrapeptide LQGV stimulates adrenal glucocorticosteroid production through activation of the ACTH receptor with consequent glucocorticoid receptor activation and immunosuppression in C57BL/6 mice.


[Cost and cost-effectiveness in the treatment of peripheral arterial occlusion disease - what is proven?].
This overview comments on the health-care relevance of peripheral arterial occlusive disease (PAOD) in patients with intermittent claudication (IC) and critical limb ischaemia (CLI). We evaluated different treatment modalities in terms of cost-effectiveness. For the literature review, the Medline database (PubMed) was searched under the key words "critical limb ischemia AND cost", "critical limb ischemia AND economy", "peripheral arterial disease AND cost", "peripheral arterial disease AND economy". In the years 2005 to 2009, the hospitalisations of patients with PAOD rose disproportionately in Germany by 20 %, to 483,961 hospital admissions. By comparison, hospital admissions altogether increased by only 8 %. The average in-patient costs were estimated to be approximately € 5000 per PAOD-patient - a rather conservative estimate. For the patient with IC the economic data position is clear, supervised exercise training is by far the most cost-effective treatment option, followed by percutaneous transluminal angioplasty (PTA) and finally the peripheral bypass. In accordance with the guidelines of the UK, the latter is therefore indicated only if PTA fails or is technically not possible. In patients with CLI, the situation is not obvious. Indeed, a short-term economic advantage can be calculated for the PTA, the long-term comparison of both methods, however, is impossible due to insufficient data. In addition, the risk factors for the patient have to be included in the calculation. This was indeed demonstrated in the short-term, but could not be analysed in the long-term follow-up. The issue of greater cost-effectiveness of open or endovascular treatment in patients with CLI is uncertain, the studies and patient populations are too heterogeneous. Further studies are urgently needed to structure the sequence of the various treatment options in guidelines and clinical pathways.


Patient selection and improved technical factors in small-vessel bypass procedures of the lower extremity.
Thirty-two small-vessel bypasses were constructed as limb-salvage procedures. The one month patency rate was 72 percent and the one year cumulative patency rate was 55 percent. Preoperative, intraoperative, and postoperative angiography was performed in most cases and the results correlated with the ultimate fate of the graft. Preoperative angiography is critical in determining the location of a suitable small vessel, including the peroneal artery, and the quality of the runoff. Intraoperative angiography is required to delineate correctable intraoperative defects usually appearing at the distal anastomotic area. Additionally, failure to demonstrate runoff or a pedal arch can help support a decision not to re-explore a graft should early closure occur. Postoperative angiography is essential to validate clinical success with graft patency and function. It also serves to discover potential graft defects that might otherwise lead to closure and potential limb loss. Selected cases of failed small-vessel bypass grafts may be salvaged by thrombectomy with or without graft revision. Small-vessel bypass is generally contraindicated if there is extensive tissue necrosis and infection extending into the proximal foot. In cases where the necrotizing infection is localized, particularly to the forefoot, then open drainage, debridement, or amputation should be performed together with small-vessel bypass. Finally, the risks indigenous to small-vessel bypass procedures demand optimal patient selection and exquisite operative technique.


Nanoscale Surface Modifications of Orthopaedic Implants: State of the Art and Perspectives.
Orthopaedic implants such as the total hip or total knee replacement are examples of surgical interventions with postoperative success rates of over 90% at 10 years. Implant failure is associated with wear particles and pain that requires surgical revision. Improving the implant - bone surface interface is a key area for biomaterial research for future clinical applications. Current implants utilise mechanical, chemical or physical methods for surface modification. A review of all literature concerning the nanoscale surface modification of orthopaedic implant technology was conducted. The techniques and fabrication methods of nanoscale surface modifications are discussed in detail, including benefits and potential pitfalls. Future directions for nanoscale surface technology are explored. Future understanding of the role of mechanical cues and protein adsorption will enable greater flexibility in surface control. The aim of this review is to investigate and summarise the current concepts and future directions for controlling the implant nanosurface to improve interactions.


Targeted 25-hydroxyvitamin D concentration measurements and vitamin D3 supplementation can have important patient and public health benefits.
Over the past two decades, many studies reported the benefits of higher 25-hydroxyvitamin D [25(OH)D] concentrations for nonskeletal effects. Researchers found significant benefits in reducing risk of acute respiratory tract infections, many types of cancer, type 2 diabetes mellitus, premature death, and adverse pregnancy and birth outcomes. In addition, 25(OH)D concentrations are low for various reasons in several categories of people, including the obese, those with dark skin living at higher latitudes, the elderly, and those who do not eat much eggs, fish, meat, or vitamin D fortified milk. Measuring 25(OH)D concentrations is one way to both increase the awareness of vitamin D's importance in maintaining good health and to encourage vitamin D supplementation or increased solar ultraviolet-B exposure to sustain well-being throughout life by reducing disease incidence. Although 20 ng/ml seems adequate to reduce risk of skeletal problems and acute respiratory tract infections, concentrations above 30 ng/ml have been associated with reduced risk of cancer, type 2 diabetes mellitus, and adverse pregnancy and birth outcomes. Thus, judicious testing of 25(OH)D concentrations could reduce disease incidence and make treatment expenditures more cost-effective.


Predicting the duration of sickness absence for patients with common mental disorders in occupational health care.
This study attempted to determine the factors that best predict the duration of absence from work among employees with common mental disorders. A cohort of 188 employees, of whom 102 were teachers, on sick leave with common mental disorders was followed for 1 year. Only information potentially available to the occupational physician during a first consultation was included in the predictive model. The predictive power of the variables was tested using Cox's regression analysis with a stepwise backward selection procedure. The hazard ratios (HR) from the final model were used to deduce a simple prediction rule. The resulting prognostic scores were then used to predict the probability of not returning to work after 3, 6, and 12 months. Calculating the area under the curve from the ROC (receiver operating characteristic) curve tested the discriminative ability of the prediction rule. The final Cox's regression model produced the following four predictors of a longer time until return to work: age older than 50 years [HR 0.5, 95% confidence interval (95% CI) 0.3-0.8], expectation of duration absence longer than 3 months (HR 0.5, 95% CI 0.3-0.8), higher educational level (HR 0.5, 95% CI 0.3-0.8), and diagnosis depression or anxiety disorder (HR 0.7, 95% CI 0.4-0.9). The resulting prognostic score yielded areas under the curves ranging from 0.68 to 0.73, which represent acceptable discrimination of the rule. A prediction rule based on four simple variables can be used by occupational physicians to identify unfavorable cases and to predict the duration of sickness absence.


Finite size effects of ionic species sensitively determine load bearing capacities of lubricated systems under combined influence of electrokinetics and surface compliance.
The behaviour and health of lubricated systems in various natural and artificial settings are often characterized by their load bearing capacity. This capacity stemming from the lift force associated with confined fluid flow can be significantly altered due to surface compliance and electrokinetic effects. Here, we highlight the influence of finite size of the ionic species participating in electrokinetic transport with substrate compliance in determining the electromechanical characteristics of lubricated systems. With these new considerations, anomalous trends previously observed for the load bearing capacity corresponding to high values of zeta potential are corrected. Simultaneously, trends associated with the finite ionic size are also found to be reversed, but fall in line with the consistent theory. Importantly, despite an intricate interplay among the various influences - electrokinetic, hydrodynamic, geometric, and elastic - previously established trends due to geometric (non-parallel slider geometry) and elastic effects are found to persist. Specifically, in the presence of electrokinetic effects, an increase in the obliqueness of the slider geometry results in lower values of load bearing capacity while an increase in the stiffness leads to higher values. These results point to a certain robustness in the overall theory and it is hoped that they can contribute to better practical designs of slider bearings and an improved understanding of lubricated sliding surfaces in biological settings.


Eicosapentaenoic acid triggers Ca2+ release and Ca2+ influx in mouse cerebral cortex endothelial bEND.3 cells.
Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca2+. Although EPA has been shown to cause human EC cytosolic Ca2+ elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca2+ concentration. EPA was shown to cause intracellular Ca2+ release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca2+ pool(s) appeared to encompass and was larger than the Ca2+ pool mobilized by sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition by cyclopiazonic acid. EPA also opened a Ca2+ influx pathway pharmacologically distinct from store-operated Ca2+ influx. Surprisingly, EPA-triggered Ca2+ influx was Ni2+-insensitive; and EPA did not trigger Mn2+ influx. Further, EPA-triggered Ca2+ influx did not involve Na+-Ca2+ exchangers. Thus, our results suggest EPA triggered unusual mechanisms of Ca2+ release and Ca2+ influx in EC.


Treating complicated grief.
The death of a loved one is one of life's greatest, universal stressors to which most bereaved individuals successfully adapt without clinical intervention. For a minority of bereaved individuals, grief is complicated by superimposed problems and healing does not occur. The resulting syndrome of complicated grief causes substantial distress and functional impairment even years after a loss, yet knowing when and how to intervene can be a challenge. To discuss the differential diagnosis, risk factors for and management of complicated grief based on available evidence and clinical observations. MEDLINE was searched from January 1990 to October 2012. Additional citations were procured from references of select research and review articles. Available treatment studies targeting complicated grief were included. A strong research literature led to inclusion of complicated grief in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (termed persistent complex bereavement disorder as a subtype of other specified trauma and stressor-related disorders), although it is a condition for which more research is formally recommended, and there is still ongoing discussion about the optimal name and diagnostic criteria for the disorder. Reliable screening instruments are available, and the estimated prevalence rate is 7% of bereaved people. Randomized controlled data support the efficacy of a targeted psychotherapy including elements that foster resolution of complicating problems and facilitate the natural healing process. Preliminary studies suggest antidepressant medications may be helpful. Individuals with complicated grief have greater risk of adverse health outcomes, should be diagnosed and assessed for suicide risk and comorbid conditions such as depression and posttraumatic stress disorder, and should be considered for treatment.


Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS).
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease affecting spinal cord motoneurons (MN) with an associative connection to Frontotemporal Lobar Dementia (FTLD). The endoplasmic reticulum (ER) bound Sigma-1 Receptor (S1R) chaperone protein localizes to specialized ER cisternae within 10 nm of the plasma membrane in spinal cord ventral horn cholinergic post synaptic C-terminals. Removal of the S1R gene in the Superoxide Dismutase-1 (SOD-1) mouse model of ALS exacerbated the neurodegenerative condition and resulted in a significantly reduced longevity when compared to the SOD-1/S1R wild type (WT) mouse. The proposed amelioration of the ALS phenotype by the S1R is likely due to a "brake" on excitation of the MN as evidenced by a reduction in action potential generation in the MN of the WT when compared to the S1R KO mouse MN. Although the precise signal transduction pathway(s) regulated by the S1R in the MN has/have not been elucidated at present, it is likely that direct or indirect functional interactions occur between the S1R in the ER cisternae with voltage gated potassium channels and/or with muscarinic M2 receptor signaling in the post synaptic plasma membrane. Possible mechanisms for regulation of MN excitability by S1R are discussed.


Changes in joint coupling and variability during walking following tibialis posterior muscle fatigue.
The tibialis posterior muscle is believed to play a key role in controlling foot mechanics during the stance phase of gait. However, an experiment involving localised tibialis posterior muscle fatigue, and analysis of discrete rearfoot and forefoot kinematic variables, indicated that reduced force output of the tibialis posterior muscle did not alter rearfoot and forefoot motion during gait. Thus, to better understand how muscle fatigue affects foot kinematics and injury potential, the purpose of this study was to reanalyze the data and investigate shank, rearfoot and forefoot joint coupling and coupling variability during walking. Twenty-nine participants underwent an exercise fatigue protocol aimed at reducing the force output of tibialis posterior. An eight camera motion analysis system was used to evaluate 3 D shank and foot joint coupling and coupling variability during treadmill walking both pre- and post-fatigue. The fatigue protocol was successful in reducing the maximal isometric force by over 30% and a concomitant increase in coupling motion of the shank in the transverse plane and forefoot in the sagittal and transverse planes relative to frontal plane motion of the rearfoot. In addition, an increase in joint coupling variability was measured between the shank and rearfoot and between the rearfoot and forefoot during the fatigue condition. The reduced function of the tibialis posterior muscle following fatigue resulted in a disruption in typical shank and foot joint coupling patterns and an increased variability in joint coupling. These results could help explain tibialis posterior injury aetiology.


Gas-phase kinetics of chlorosilylene reactions II. ClSiH + C2H4: absolute rate measurements and quantum chemical and RRKM calculations for the prototype pi addition reaction.
Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, are carried out to obtain rate constants for its bimolecular reaction with ethene, C(2)H(4), in the gas-phase. The reaction is studied over the pressure range 0.13-13.3 kPa (with added SF(6)) at five temperatures in the range 296-562 K. The second order rate constants, obtained by extrapolation to the high pressure limits at each temperature, fitted the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1)) = (-10.55+/-0.10) + (3.86 +/- 0.70) kJ mol(-1)/RT ln10. The Arrhenius parameters correspond to a loose transition state and the rate constant at room temperature is 43% of that for SiH(2) + C(2)H(4), showing that the deactivating effect of Cl-for-H substitution in the silylene is not large. Quantum chemical calculations of the potential energy surface for this reaction at the G3MP2//B3LYP level show that, as well as 1-chlorosilirane, ethylchlorosilylene is a viable product. The calculations reveal how the added effect of the Cl atom on the divalent state stabilisation of ClSiH influences the course of this reaction. RRKM calculations of the reaction pressure dependence suggest that ethylchlorosilylene should be the main product. The results are compared and contrasted with those of SiH(2) and SiCl(2) with C(2)H(4).


Death by Suicide Within 1 Week of Hospital Discharge: A Retrospective Study of Root Cause Analysis Reports.
There is a high risk for death by suicide after discharge from an inpatient mental health unit. To better understand system and organizational factors associated with postdischarge suicide, we reviewed root cause analysis reports of suicide within 7 days of discharge from across all Veterans Health Administration inpatient mental health units between 2002 and 2015. There were 141 reports of suicide within 7 days of discharge, and a large proportion (43.3%, n = 61) followed an unplanned discharge. Root causes fell into three major themes including challenges for clinicians and patients after the established process of care, awareness and communication of suicide risk, and flaws in the established process of care. Flaws in the design and execution of processes of care as well as deficits in communication may contribute to postdischarge suicide. Inpatient teams should be aware of the potentially heightened risk for suicide among patients with unplanned discharges.


Nucleation landscape of biomolecular condensates.
All structures within living cells must form at the right time and place. This includes condensates such as the nucleolus, Cajal bodies and stress granules, which form via liquid-liquid phase separation of biomolecules, particularly proteins enriched in intrinsically disordered regions (IDRs)1,2. In non-living systems, the initial stages of nucleated phase separation arise when thermal fluctuations overcome an energy barrier due to surface tension. This phenomenon can be modelled by classical nucleation theory (CNT), which describes how the rate of droplet nucleation depends on the degree of supersaturation, whereas the location at which droplets appear is controlled by interfacial heterogeneities3,4. However, it remains unknown whether this framework applies in living cells, owing to the multicomponent and highly complex nature of the intracellular environment, including the presence of diverse IDRs, whose specificity of biomolecular interactions is unclear5-8. Here we show that despite this complexity, nucleation in living cells occurs through a physical process similar to that in inanimate materials, but the efficacy of nucleation sites can be tuned by their biomolecular features. By quantitatively characterizing the nucleation kinetics of endogenous and biomimetic condensates in living cells, we find that key features of condensate nucleation can be quantitatively understood through a CNT-like theoretical framework. Nucleation rates can be substantially enhanced by compatible biomolecular (IDR) seeds, and the kinetics of cellular processes can impact condensate nucleation rates and specificity of location. This quantitative framework sheds light on the intracellular nucleation landscape, and paves the way for engineering synthetic condensates precisely positioned in space and time.


Lack of taxonomic differentiation in an apparently widespread freshwater isopod morphotype (Phreatoicidea: Mesamphisopidae: Mesamphisopus) from South Africa.
The unambiguous identification of phreatoicidean isopods occurring in the mountainous southwestern region of South Africa is problematic, as the most recent key is based on morphological characters showing continuous variation among two species: Mesamphisopus abbreviatus and M. depressus. This study uses variation at 12 allozyme loci, phylogenetic analyses of 600 bp of a COI (cytochrome c oxidase subunit I) mtDNA fragment and morphometric comparisons to determine whether 15 populations are conspecific, and, if not, to elucidate their evolutionary relationships. Molecular evidence suggested that the most easterly population, collected from the Tsitsikamma Forest, was representative of a yet undescribed species. Patterns of differentiation and evolutionary relationships among the remaining populations were unrelated to geographic proximity or drainage system. Patterns of isolation by distance were also absent. An apparent disparity among the extent of genetic differentiation was also revealed by the two molecular marker sets. Mitochondrial sequence divergences among individuals were comparable to currently recognized intraspecific divergences. Surprisingly, nuclear markers revealed more extensive differentiation, more characteristic of interspecific divergences. This disparity and the mosaic pattern of differentiation may be driven by stochastic population crashes and genetic bottlenecks (caused by seasonal habitat fluctuations), coupled with genetic drift.


A Type III restriction-modification system in Mycoplasma mycoides subsp. capri.
The sequenced genome of Mycoplasma mycoides subsp. capri revealed the presence of a Type III restriction-modification system (MmyCI). The methyltransferase (modification) subunit of MmyCI (M.MmyCI) was shown to recognize the sequence 5'-TGAG-3' and methylate the adenine. The coding region of the methyltransferase gene contains 12 consecutive AG dinucleotide repeats that result in a translational termination at a TAA codon immediately beyond the repeat region. This strain does not have MmyCI activity. A clone was found with 10 AG repeats such that the gene is in frame, and this strain has MmyCI activity, suggesting that the expression of the MmyCI methyltransferase may be phase variable.


Defining Value for Pancreatic Surgery in Early-Stage Pancreatic Cancer.
Value-based care is increasingly important, with rising health care costs and advances in cancer treatment leading to greater survival for patients with cancer. Regionalization of surgical care for pancreatic cancer has been extensively studied as a strategy to improve perioperative outcomes, but investigation of long-term outcomes relative to health care costs (ie, value) is lacking. To identify patient and hospital characteristics associated with improved overall survival, decreased costs, and greater value among patients with pancreatic cancer undergoing curative resection. This retrospective cohort study identified 2786 patients with stages I to II pancreatic cancer who underwent pancreatic resection at 157 hospitals from January 1, 2004, through December 31, 2012. The study used the California Cancer Registry, which collects data from all California residents newly diagnosed with cancer, linked to the Office of Statewide Health Planning and Development database, which collects administrative data from all California licensed hospitals. Data were analyzed from November 11, 2017, through September 4, 2018. Pancreatic resection at high-volume and/or National Cancer Institute (NCI)-designated cancer centers. The primary outcomes were overall survival, surgical hospitalization costs, and value. High value was defined as the fourth quintile or higher for survival and the second quintile or less for costs. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation and inflation. Multivariable regression models were used to determine factors associated with overall survival, costs, and high value. Among the 2786 patients included (1394 [50.0%] male; mean [SD] age, 67.0 [10.7] years), postoperative chemotherapy (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.64-0.79; P < .001) and high-volume centers (aHR, 0.78; 95% CI, 0.61-0.99; P = .04) were associated with greater overall survival. Higher Elixhauser comorbidity index scores (estimate, 0.006; 95% CI, 0.003-0.008), complications (estimate, 0.22; 95% CI, 0.17-0.27), readmissions (estimate, 0.34; 95% CI, 0.29-0.39), and longer lengths of stay (estimate, 0.03; 95% CI, 0.03-0.04) were associated with higher costs (P < .001), whereas postoperative chemotherapy was associated with lower costs (estimate, -0.06; 95% CI, -0.11 to -0.02; P = .006). National Cancer Institute-designated and high-volume centers were not associated with costs. Although grades III and IV tumors (odds ratio [OR], 0.65; 95% CI, 0.39-0.91; P = .001), T3 category disease (OR, 0.71; 95% CI, 0.46-0.95; P = .005), complications (OR, 0.68; 95% CI, 0.49-0.86; P < .001), readmissions (OR, 0.64; 95% CI, 0.44-0.84; P < .001), and length of stay (OR, 0.82; 95% CI, 0.78-0.85; P < .001) were inversely associated with high-value care, NCI designation (OR, 1.07; 95% CI, 0.66-1.49; P = .74) and high-volume centers (OR, 1.08; 95% CI, 0.54-1.61; P = .07) were not. In this study, high-value care was associated with important patient characteristics and postoperative outcomes. However, NCI-designated and high-volume centers were not associated with greater value. These data suggest that targeted measures to enhance value may be needed in these centers.


Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model.
Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation is hypothesized to be involved as some studies have shown elevated blood OT and altered OT receptor expression in patients. A "Complete Deletion" (CD) mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These CD mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether OT dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an OT receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in CD mice. Thus, increased OT signaling is not acutely responsible for this phenotype. We also evaluated OT receptor and serotonin transporter availability in regions related to fear learning, memory and sociability using autoradiography in wild type and CD mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in OT receptor expression in the lateral septal nucleus and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.


Subjective sense of memory strength and the objective amount of information accurately remembered are related to distinct neural correlates at encoding.
Although commonly used, the term memory strength is not well defined in humans. Besides durability, it has been conceptualized by retrieval characteristics, such as subjective confidence associated with retrieval, or objectively, by the amount of information accurately retrieved. Behaviorally, these measures are not necessarily correlated, indicating that distinct neural processes may underlie them. Thus, we aimed at disentangling neural activity at encoding associated with either a subsequent subjective sense of memory strength or with a subsequent objective amount of information remembered. Using functional magnetic resonance imaging (fMRI), participants were scanned while incidentally encoding a series of photographs of complex scenes. The next day, they underwent two memory tests, quantifying memory strength either subjectively (confidence on remembering the gist of a scene) or objectively (the number of details accurately remembered within a scene). Correlations between these measurements were mutually partialed out in subsequent memory analyses of fMRI data. Results revealed that activation in left ventral lateral prefrontal cortex and temporoparietal junction predicted subsequent confidence ratings. In contrast, parahippocampal and hippocampal activity predicted the number of details remembered. Our findings suggest that memory strength may reflect a functionally heterogeneous set of (at least two) phenomena. One phenomenon appears related to prefrontal and temporoparietal top-down modulations, resulting in the subjective sense of memory strength that is potentially based on gist memory. The other phenomenon is likely related to medial-temporal binding processes, determining the amount of information accurately encoded into memory. Thus, our study dissociated two distinct phenomena that are usually described as memory strength.


Structurally dependent redox property of ribonucleotide reductase subunit p53R2.
p53R2 is a newly identified small subunit of ribonucleotide reductase (RR) and plays a key role in supplying precursors for DNA repair in a p53-dependent manner. Currently, we are studying the redox property, structure, and function of p53R2. In cell-free systems, p53R2 did not oxidize a reactive oxygen species (ROS) indicator carboxy-H2DCFDA, but another class I RR small subunit, hRRM2, did. Further studies showed that purified recombinant p53R2 protein has catalase activity, which breaks down H2O2. Overexpression of p53R2 reduced intracellular ROS and protected the mitochondrial membrane potential against oxidative stress, whereas overexpression of hRRM2 did not and resulted in a collapse of mitochondrial membrane potential. In a site-directed mutagenesis study, antioxidant activity was abrogated in p53R2 mutants Y331F, Y285F, Y49F, and Y241H, but not Y164F or Y164C. The fluorescence intensity in mutants oxidizing carboxy-H2DCFDA, in order from highest to lowest, was Y331F > Y285F > Y49F > Y241H > wild-type p53R2. This indicates that Y331, Y285, Y49, and Y241 in p53R2 are critical residues involved in scavenging ROS. Of interest, the ability to oxidize carboxy-H2DCFDA indicated by fluorescence intensity was negatively correlated with RR activity from wild-type p53R2, mutants Y331F, Y285F, and Y49F. Our findings suggest that p53R2 may play a key role in defending oxidative stress by scavenging ROS, and this antioxidant property is also important for its fundamental enzymatic activity.


Comparing segmentation by time and by motion in visual search: an FMRI investigation.
Brain activity was recorded while participants engaged in a difficult visual search task for a target defined by the spatial configuration of its component elements. The search displays were segmented by time (a preview then a search display), by motion, or were unsegmented. A preparatory network showed activity to the preview display, in the time but not in the motion segmentation condition. A region of the precuneus showed (i) higher activation when displays were segmented by time or by motion, and (ii) correlated activity with larger segmentation benefits behaviorally, regardless of the cue. Additionally, the results revealed that success in temporal segmentation was correlated with reduced activation in early visual areas, including V1. The results depict partially overlapping brain networks for segmentation in search by time and motion, with both cue-independent and cue-specific mechanisms.


Parent-child separation: the relationship between separation and psychological adjustment among Chinese rural children.
The current study aimed to explore the characteristics of psychological adjustment among Chinese left-behind children (LBC) in rural areas, and to examine the association between separation duration from parent/parents (SDP) and children's psychological adjustment and the extent to which personality mediates this hypothesized link. We surveyed 534 rural children and adolescents aged 10-17 years at school (440 LBC and 94 non-LBC) in 2013, who were selected for participation using stratified cluster sampling from two counties in Chongqing, China. Measures used included socio-demographic variables, age at the commencement and end of the separation from parents, the revised Chinese Juvenile Eysenck Personality Questionnaire, and the Adolescent Psychological Adaptability Scale. Most children (82.4%) had experienced separation from parents. t test results showed a marginally significant difference (p = .08) in psychological adjustment between LBC (mean = 64.44, SD = 8.62) and non-LBC (mean = 66.16, SD = 9.26). LBC's mean SDP was 5.64 years (SD = 3.90). Correlation analysis showed that children's SDP was negatively associated with psychological adjustment. Structural equation modeling showed that neuroticism, but not extraversion or psychoticism, fully mediated the link between children's SDP and psychological adjustment. Personality (neuroticism) is one of the mediating pathways through which long-term SDP may predict poor psychological adjustment among children. Given the detrimental impact of long-term SDP, interventions should target the mediating pathway to buffer against the negative impact of parental separation on the affected rural children and to improve their mental health.


Paramedic Application of a Triage Sieve: A Paper-Based Exercise.
Introduction Triage is the systematic prioritization of casualties when there is an imbalance between the needs of these casualties and resource availability. The triage sieve is a recognized process for prioritizing casualties for treatment during mass-casualty incidents (MCIs). While the application of a triage sieve generally is well-accepted, the measurement of its accuracy has been somewhat limited. Obtaining reliable measures for triage sieve accuracy rates is viewed as a necessity for future development in this area. The goal of this study was to investigate how theoretical knowledge acquisition and the practical application of an aide-memoir impacted triage sieve accuracy rates. Two hundred and ninety-two paramedics were allocated randomly to one of four separate sub-groups, a non-intervention control group, and three intervention groups, which involved them receiving either an educational review session and/or an aide-memoir. Participants were asked to triage sieve 20 casualties using a previously trialed questionnaire. The study showed the non-intervention control group had a correct accuracy rate of 47%, a similar proportion of casualties found to be under-triaged (37%), but a significantly lower number of casualties were over-triaged (16%). The provision of either an educational review or aide-memoir significantly increased the correct triage sieve accuracy rate to 77% and 90%, respectively. Participants who received both the educational review and aide-memoir had an overall accuracy rate of 89%. Over-triaged rates were found not to differ significantly across any of the study groups. This study supports the use of an aide-memoir for maximizing MCI triage accuracy rates. A "just-in-time" educational refresher provided comparable benefits, however its practical application to the MCI setting has significant operational limitations. In addition, this study provides some guidance on triage sieve accuracy rate measures that can be applied to define acceptable performance of a triage sieve during a MCI. Cuttance G , Dansie K , Rayner T . Paramedic application of a triage sieve: a paper-based exercise. Prehosp Disaster Med. 2017;32(1):3-13.


Serum amyloid A immunohistochemical staining patterns in hepatitis.
Serum amyloid A is an acute phase reactant that is produced by hepatocytes in response to either inflammatory or neoplastic conditions. Because inflammatory adenomas produce this protein, serum amyloid A immunohistochemistry has been used in the evaluation of hepatocellular neoplasms. However, studies evaluating the expression of this protein in hepatitis are lacking. The aim of this study was to perform serum amyloid A immunostains on medical liver biopsy specimens of patients with common chronic liver diseases and correlate them with disease activity and stage. We performed serum amyloid A immunostains on 160 medical liver biopsies, including 100 cases of hepatitis C virus infection at different stages (20 cases of each) and 20 cases each of hepatitis B viral infection, steatohepatitis and autoimmune hepatitis. The extent and location of staining was recorded and correlated with grade, stage and laboratory values (transaminases, bilirubin and viral load). Data were analysed using the Cochran-Mantel-Haenszel χ2 test for trend. Serum amyloid A staining was present in 130 (81%) cases and was limited to zone 3 perivenular hepatocytes in 66 (41%). Biopsy specimens with less fibrosis and/or mild portal inflammation showed significantly more staining than those with cirrhosis (P < 0.001), or at least moderate inflammatory activity (P < 0.001). There was no significant association between lobular inflammation (P = 0.06), bilirubin levels or viral load and immunohistochemical staining for serum amyloid A. Our results show that liver biopsy specimens with mildly active chronic hepatitis, early fibrosis and normal serum transaminases show more serum amyloid A immunopositivity compared with cases with more inflammatory activity, fibrosis or transaminitis. These findings indicate that serum amyloid A is expressed primarily in the early phases of disease and might influence progression and/or response to treatment.


Validation of a diagnostic algorithm for adult tuberculous meningitis.
Tuberculous meningitis (TBM) remains difficult to diagnose. We prospectively evaluated a diagnostic algorithm for TBM in 205 HIV-negative patients with meningitis and a low CSF glucose. Patients were classified as having TBM or bacterial meningitis (BM) by two diagnostic methods: logistic regression method (LRM) and classification and regression tree (CART). We performed analyses of TBM versus BM and TBM versus non-TBM in all patients and in patients with microbiologically confirmed diagnoses. Diagnostic sensitivities for TBM were 99% (LRM) and 87% (CART). For BM, diagnostic sensitivities were 81.5% (LRM) and 86.5% (CART) in the primary analysis and 86.5% (LRM) and 74% (CART) in the secondary analysis. In microbiologically confirmed cases, similar rates were achieved. These figures are superior to microbiological confirmation rates in routine laboratories and support the use of this algorithm in high-prevalence TB settings with limited diagnostic facilities. Validation in an HIV-endemic setting is required.