Dimethylmercury in Floodwaters of Mercury Contaminated Rice Paddies.
Dimethyl mercury (CH3HgCH3, DMeHg) has been observed in upwelling marine environments and the deep ocean. However, little is known about the occurrence and mechanisms of DMeHg formation in freshwater environments. In this study, concentrations of dissolved gaseous DMeHg were investigated in floodwaters of rice paddies in China that have been contaminated by mercury from mining. Values of DMeHg in rice paddies were compared with measurements from nearshore surface seawater in the Bohai Gulf. High concentrations of dissolved gaseous DMeHg occurred in rice paddies. Average DMeHg concentration was 12 ± 22 pg L-1 with range of 0.39 to 91 pg L-1 in rice paddies at Shuijing, China, a site impacted by an abandoned mercury mine. These concentrations are comparable to those previously observed in the deep seawater and coastal upwelling environments (2.3-115pg L-1). An alkaline environment was found to be necessary for DMeHg formation in rice paddies. Associated incubation experiments showed that production of DMeHg in paddy soil was limited by Hg availability. Although iron amendments accelerated the production of gaseous methylmercury (MeHg) species to floodwaters, available Hg2+ is crucial for this production in flooded rice paddies. These observations are the first to demonstrate the occurrence of DMeHg and reveal factors affecting DMeHg production in rice paddies. Given the high volatility of DMeHg, these measurements also suggest a source for observations of MeHg in atmospheric deposition and advance understanding of a potentially important aspect of the biogeochemical cycling of Hg.


Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.
In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA.


Functionalization of strongly interacting magnetic nanocubes with (thermo)responsive coating and their application in hyperthermia and heat-triggered drug delivery.
Herein, we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermoresponsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR), but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermoresponsive shell is composed of poly(N-isopropylacrylamide-co-polyethylene glycolmethyl ether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.


Mothers' cafeteria diet induced sex-specific changes in fat content, metabolic profiles, and inflammation outcomes in rat offspring.
"Western diet" containing high concentrations of sugar and fat consumed during pregnancy contributes to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet in animals, a cafeteria (CAF) diet is used. We hypothesized that CAF diet given to rats before, and during pregnancy and lactation differently influences fat content, metabolic and inflammation profiles in offspring. Females were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25), body composition, fat contents were measured, and blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet lead to sex-specific alterations in offspring. At PND25, CAF offspring had: (1) higher percentage of fat content, and were lighter; (2) sex-specific differences in levels of glucose; (3) higher levels of interleukin 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); (4) sex-specific differences in concentration of IL-6 and TNF-α, with an increase in CAF females; (5) higher level of IL-10 in both sexes, with a more pronounced increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet.


SU-E-I-13: Evaluation of CT Number with Changing Scan Parameters for Nucletron Simulix Evolution CBCT.
To quantify the variation in CT number generated by the Simulix Evolution CBCT with changes in scan length and phantom thickness. Three phantoms were used in this study: CIRS Model 610 AAPM CT Phantom, Gammex 467 Tissue Characterization Phantom, and Catphan 600 phantom. The AAPM Phantom was used to assess the variation of HU with phantom thickness. Scans were acquired with two field size settings (full- and half-beam) with and without a 3.5 cm thick ring. The Catphan and Gammex phantoms were used to assess the Simulix's capability of producing a consistent CT-to-ED conversion table with different scan lengths, ranging from 1 cm (very thin) to 20 cm (clinical use). The data were also compared to data acquired with our in-house CT Sim (GE HiLite LightSpeed 16 slice). The AAPM phantom scans with and without the ring yielded an average difference in HU of 145 HU (full-beam) and 74 HU (half-beam) for each of five inserts. The HU for Cortical Bone (SB3) [largest Gammex electron density insert; 1.69] ranged from 923 to 1170 HU for the 4 cm and 1 cm scan lengths, respectively. The HU for Teflon [largest Catphan electron density insert; 1.867] ranged from 657 to 951 for the 20 cm and 1 cm scan lengths, respectively. The HU for air in Catphan ranged from -749 to -905, and the HU for LDPE [electron density 0.944] ranged from -82 to -42, for the 20 cm and 1 cm scan lengths, respectively. Results show a large variability in the calculated CT number with differences in phantom thickness, as evidenced by the results with the AAPM phantom. In addition, there appears to be a dependence on scan length, attributed to increased scatter contribution. Further tests will be done to evaluate the appropriateness of the use of the Simulix CBCT unit for heterogeneity corrected external beam treatment planning. The author has received no funding during the course of this research.


The impact on health of employment and welfare transitions for those receiving out-of-work disability benefits in the UK.
Employment status has a dynamic relationship with health and disability. There has been a striking increase in the working age population receiving out-of-work disability benefits in many countries, including the UK. In response, recent UK welfare reforms have tightened eligibility criteria and introduced new conditions for benefit receipt linked to participation in return-to-work activities. Positive and negative impacts have been suggested but there is a lack of high quality evidence of the health impact when those receiving disability benefits move towards labour market participation. Using four waves of the UK's Understanding Society panel survey (2009-2013) three different types of employment and welfare transition were analysed in order to identify their impact on health. A difference-in-difference approach was used to compare change between treatment and control groups in mental and physical health using the SF-12. To strengthen causal inference, sensitivity checks for common trends used pre-baseline data and propensity score matching. Transitions from disability benefits to employment (n = 124) were associated on average with an improvement in the SF12 mental health score of 5.94 points (95% CI = 3.52-8.36), and an improvement in the physical health score of 2.83 points (95% CI = 0.85-4.81) compared with those remaining on disability benefits (n = 1545). Transitions to unemployed status (n = 153) were associated with a significant improvement in mental health (3.14, 95% CI = 1.17-5.11) but not physical health. No health differences were detected for those who moved on to the new out-of-work disability benefit. It remains rare for disability benefit recipients to return to the labour market, but our results indicate that for those that do, such transitions may improve health, particularly mental health. Understanding the mechanisms behind this relationship will be important for informing policies to ensure both work and welfare are 'good for health' for this group.


Quality, but not quantity of physical activity is associated with metal ion concentrations in unilateral hip resurfacing.
Little is known about the influence of physical activity (PA) on metal ion concentrations in subjects with metal-on-metal hip arthroplasty. Implant wear is thought to be a function of use and thus of patient activity levels. It is hypothesized that daily habitual PA of patients with hip resurfacing arthroplasty (HRA) is associated with metal ion concentrations. Therefore a study was conducted in patients with a unilateral HRA at 10-years follow-up. Blood metal ion concentrations were determined. An acceleration-based activity monitor was used to measure PA in daily life. The cohort consisted of 12 males (75%) and 4 females (25%) with a median age at surgery of 55.5 ± 9.7 years [43.0-67.9] and a median follow-up of 9.9 ± 1.0 years [9.1-10.9]. The median cobalt and chromium ion concentrations were 25 ± 13 and 38 ± 28 nmol/L. A significant association between sit-stand transfers and high-intensity peaks with cobalt ion concentrations were found. Regarding PA and metal ion concentrations as a proxy of wear in HRA, specific activities like transfers or qualitative aspects of activity behavior like intensity, seem to matter more than the quantity of low-intensity activities like walking or cycling. This suggests that patients may safely engage in such activities to achieve important general health benefits and quality of life.


Orbitofrontal cortex uses distinct codes for different choice attributes in decisions motivated by curiosity.
Decision makers are curious and consequently value advance information about future events. We made use of this fact to test competing theories of value representation in area 13 of orbitofrontal cortex (OFC). In a new task, we found that monkeys reliably sacrificed primary reward (water) to view advance information about gamble outcomes. While monkeys integrated information value with primary reward value to make their decisions, OFC neurons had no systematic tendency to integrate these variables, instead encoding them in orthogonal manners. These results suggest that the predominant role of the OFC is to encode variables relevant for learning, attention, and decision making, rather than integrating them into a single scale of value. They also suggest that OFC may be placed at a relatively early stage in the hierarchy of information-seeking decisions, before evaluation is complete. Thus, our results delineate a circuit for information-seeking decisions and suggest a neural basis for curiosity.


Single-cell dissection of transcriptional heterogeneity in human colon tumors.
Cancer is often viewed as a caricature of normal developmental processes, but the extent to which its cellular heterogeneity truly recapitulates multilineage differentiation processes of normal tissues remains unknown. Here we implement single-cell PCR gene-expression analysis to dissect the cellular composition of primary human normal colon and colon cancer epithelia. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. By creating monoclonal tumor xenografts from injection of a single (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Finally, we show that the different gene-expression programs linked to multilineage differentiation are strongly associated with patient survival. We develop two-gene classifier systems (KRT20 versus CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard ratios superior to those of pathological grade and comparable to those of microarray-derived multigene expression signatures.


Gene and protein patterns of potential prion-related markers in the central nervous system of clinical and preclinical infected sheep.
The molecular pathogenic mechanisms of prion diseases are far from clear. Genomic analyses have revealed genetic biomarkers potentially involved in prion neuropathology in naturally scrapie-infected sheep, a good animal model of infectious prionopathies. However, these biomarkers must be validated in independent studies at different stages of the disease. The gene and protein expression profiles and protein distribution of six potential genetic biomarkers (i.e., CAPN6, COL1A2, COL3A1, GALA1, MT2A and MTNR1B) are presented here for both the early and terminal stages of scrapie in five different brain regions. Gene transcription changes were confirmed in the medulla oblongata, and the expression profiles were generally similar in other central nervous system regions. The changes were more substantial in clinical animals compared to preclinical animals. The expression of the CAPN6 protein increased in the spinal cord and cerebellum of the clinical and preclinical brains. The distribution of the GALA1 was identified in glial cells from the cerebellum of scrapie-infected animals, GALA1 protein expression was increased in clinical animals in the majority of regions, and the increase of MT2A was in agreement with previous reports. The downregulation of MTNR1B was especially marked in the Purkinje cells. Finally, although collagen genes were downregulated the protein immunostaining did not reveal significant changes between the scrapie-infected and control animals. In conclusion, this study of gene transcription and protein expression and distribution confirm CAPN6, GALA1, MTNR1B and MT2A as potential targets for further prion disease research.


Theta-band Oscillations in the Middle Temporal Gyrus Reflect Novel Word Consolidation.
Like many other types of memory formation, novel word learning benefits from an offline consolidation period after the initial encoding phase. A previous EEG study has shown that retrieval of novel words elicited more word-like-induced electrophysiological brain activity in the theta band after consolidation [Bakker, I., Takashima, A., van Hell, J. G., Janzen, G., & McQueen, J. M. Changes in theta and beta oscillations as signatures of novel word consolidation. Journal of Cognitive Neuroscience, 27, 1286-1297, 2015]. This suggests that theta-band oscillations play a role in lexicalization, but it has not been demonstrated that this effect is directly caused by the formation of lexical representations. This study used magnetoencephalography to localize the theta consolidation effect to the left posterior middle temporal gyrus (pMTG), a region known to be involved in lexical storage. Both untrained novel words and words learned immediately before test elicited lower theta power during retrieval than existing words in this region. After a 24-hr consolidation period, the difference between novel and existing words decreased significantly, most strongly in the left pMTG. The magnitude of the decrease after consolidation correlated with an increase in behavioral competition effects between novel words and existing words with similar spelling, reflecting functional integration into the mental lexicon. These results thus provide new evidence that consolidation aids the development of lexical representations mediated by the left pMTG. Theta synchronization may enable lexical access by facilitating the simultaneous activation of distributed semantic, phonological, and orthographic representations that are bound together in the pMTG.


Horizontal gene transfer from genus agrobacterium to the plant linaria in nature.
Genes can be transferred horizontally between prokaryotes and eukaryotes in nature. The best-studied examples occur between Agrobacterium rhizogenes and certain Nicotiana spp. To investigate possible additional cases of horizontal gene transfer in nature between Agrobacterium and plants, a real-time polymerase chain reaction-based approach was employed to screen 127 plant species, belonging to 38 families of Dicotyledones, for the presence of oncogenes homologous to the transfer DNA fragments (T-DNA) from both A. tumefaciens and A. rhizogenes. Among all of the analyzed plant species, we found that only Linaria vulgaris contained sequences homologous to the T-DNA of A. rhizogenes. All screened L. vulgaris plants from various parts of Russia contained the same homologous sequences, including rolB, rolC, ORF13, ORF14, and mis genes. The same opine gene is found in the species of Nicotiana which contain genes of A. rhizogenes. In L. vulgaris, there are two copies of T-DNA organized as a single tandem imperfect direct repeat. The plant DNA sequence of the site of integration shows similarity to a retrotransposon. This site is most likely silent, suggesting that the T-DNA is not expressed. Attempts to demonstrate expression of the T-DNA genes were negative. Our study indicates that the frequency of gene transfer and fixation in the germline from Agrobacterium to plant hosts is rare in the natural environment.


The Effect of Adding Magnesium Sulfate to Local Anesthetic in Patients Undergoing Middle Ear Surgery.
The use of local anesthesia has been proved to be beneficial in ear surgeries. This study was conducted to compare between local anesthesia alone and in combination with magnesium sulphate as an adjuvant in ear operations. This prospective study included a total of 164 cases prepared for elective ear surgeries were included. They were divided into two equal groups, group C or control group included cases who received local anesthesia alone, and group M which included cases who received local anesthesia in addition to magnesium sulphate. Ear ring block was performed in all cases. Monitoring of blood pressure, heart rate, and oxygen saturation was performed. Post-operative pain was assessed by visual analogue score. The total analgesic time and total analgesic requirement were recorded. IBM's SPSS statistics (Statistical Package for the Social Sciences) for windows (version 25, 2017) was used for statistical analysis of the collected data. Shapiro-Wilk test was used to check the normality of the data distribution. All tests were conducted with 95% confidence interval. P (probability) value < 0.05 was considered statistically significant. Charts were generated using SPSS' chart builder and Microsoft Excel for windows 2019. The onset of sensory blockade was significantly earlier in the Mg group. Mg group showed a significant decrease in intraoperative and post-operative analgesic consumption. In addition, the first request for analgesia after operation was markedly delayed in the Mg group compared to controls. Regarding intraoperative VAS, it was significantly lower in the Mg group compared to controls at 15-minute reading. Post-operative VAS was significantly lower in Mg group during the first two hours. Addition of magnesium to local anesthesia causes early onset of sensory blockade, delayed call first for analgesia, and better VAS scores during the early post-operative period.


Norovirus gastroenteritis outbreaks in military units: a systematic review.
Norovirus gastroenteritis is one of the most frequent causes of personnel unavailability in military units, being associated with significant morbidity and degradation of their operational effectiveness. The disease is usually mild but can be severe and life-threatening in young and healthy soldiers, who are prone to dehydration due to intensive daily activity. Despite its impact, the full extent of the norovirus gastroenteritis burden in military forces remains unclear. This systematic review aims to evaluate the impact and ascertain clinical and epidemiological features of norovirus outbreaks that have occurred in the military forces. The systematic review followed the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guidelines and used three databases: PubMed, Scopus, and LILACs. Papers published up to 1 September 2019 were included without restrictions if they reported one or more outbreaks in the military forces on active duty, either on national territories or deployed overseas. A total of 343 papers were retrieved from the literature search. After inclusion/exclusion criteria a total of 39 eligible papers were considered. From 1988 (first reported outbreak in the military) to 2018 more than 101 norovirus outbreaks have been reported in the military, accounting for at least 24 332 cases. Secondary transmission was emphasised as the main route of norovirus transmission in the military forces, with eating outside the military setting an important route for the primary cases. The present review highlights that norovirus gastroenteritis has been a burden to military troops both in combat and on peacekeeping operations. Norovirus disease has been shown to exact a substantial toll on mission readiness and operational effectiveness. It is noteworthy that the impact of norovirus outbreaks among military units is underestimated because the literature review retrieved information from the armed forces from only nine countries.


Menopause symptoms in HIV-infected and drug-using women.
To examine the association of HIV infection, drug use, and psychosocial stressors with type and frequency of menopause symptoms. In a cross-sectional study, HIV-infected and HIV-uninfected midlife women underwent standardized interviews on menopause status and symptoms, demographic characteristics, depressive symptoms, negative life events, and substance abuse. Body mass index (BMI), HIV serostatus, and CD4 count were measured. Associations between study variables and menopause symptoms were assessed using generalized estimating equations. Of 536 women not on hormone therapy, 48% were black, 42% were Hispanic, 54% were HIV positive, and 30% recently had used illicit drugs. The mean age was 45 +/- 5 years; 48% of the women were identified as premenopausal, and 37% were perimenopausal. Psychological symptoms were most prevalent (89%), followed by arthralgias (63%) and vasomotor symptoms (61%). Perimenopausal women reported significantly more menopause symptoms than premenopausal women (ORadj 1.34, 95% CI, 1.09-1.65). HIV-infected women were more likely to report menopause symptoms than uninfected women (ORadj 1.24, 95% CI, 1.02-1.51). Among HIV-infected women not on highly active antiretroviral therapy, symptoms decreased as the CD4 count declined. Increased menopause symptoms were significantly associated with depressive symptoms (ie, Center for Epidemiologic Studies Depression scale score > 23, ORadj1.82, 95% CI, 1.46-2.28), and with experiencing more than three negative life events (ORadj 2.08, 95% CI, 1.54-2.81). Increasing BMI (per kg/m) was also associated with more menopause symptoms (ORadj 1.03, 95% CI, 1.02-1.05). HIV-infected women reported more menopause symptoms than HIV-uninfected women, but symptoms were less frequent in women with more advanced HIV disease. Depressive symptoms and negative life events were also highly associated with symptoms. Further study of menopause symptoms and HIV-related factors is warranted. Mental health interventions may also have a role in ameliorating menopause symptoms.


Digital technology and disease surveillance in the COVID-19 pandemic: a scoping review protocol.
Infectious diseases pose a risk to public health, requiring efficient strategies for disease prevention. Digital health surveillance technologies provide new opportunities to enhance disease prevention, detection, tracking, reporting and analysis. However, in addition to concerns regarding the effectiveness of these technologies in meeting public health goals, there are also concerns regarding the ethics, legality, safety and sustainability of digital surveillance technologies. This scoping review examines the literature on digital surveillance for public health purposes during the COVID-19 pandemic to identify health-related applications of digital surveillance technologies, and to highlight discussions of the implications of these technologies. The scoping review will be guided by the framework proposed by Arksey and O'Malley and the guidelines outlined by Colquhoun et al and Levac et al. We will search Medline (Ovid), PsycInfo, PubMed, Scopus, CINAHL (EBSCOhost), ACM Digital Library, Google Scholar and IEEE Explore for relevant studies published between December 2019 and December 2020. The review will also include grey literature. Data will be managed and analysed through an extraction table and thematic analysis. Findings will be disseminated through traditional academic channels, as well as social media channels and research briefs and infographics. We will target our dissemination to provincial and federal public health organisations, as well as technology companies and community-based organisations managing the public response to the COVID-19 pandemic.


Temporal trends in antithrombotic treatment of real-world UK patients with newly diagnosed atrial fibrillation: findings from the GARFIELD-AF registry.
To investigate evolving patterns in antithrombotic treatment in UK patients with newly diagnosed non-valvular atrial fibrillation (AF). Prospective, multicentre, international registry. 186 primary care practices in the UK. 3482 participants prospectively enrolled in four sequential cohorts (cohort 2 (C2) n=830, diagnosed September 2011 to April 2013; cohort 3 (C3) n=902, diagnosed April 2013 to June 2014; cohort 4 (C4) n=850, diagnosed July 2014 to June 2015; cohort 5 (C5) n=900, diagnosed June 2015 to July 2016). Participants had newly diagnosed non-valvular AF and at least one risk factor for stroke, were aged ≥18, and provided informed consent. Antithrombotic treatment initiated at diagnosis, overall and according to stroke and bleeding risks. Stroke risk was retrospectively calculated using CHA2DS2-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)) and bleeding risk using HAS-BLED (hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, elderly (>65), drugs/alcohol concomitantly (1 point each)). 42.7% were women and the mean age was 74.5 years. The median CHA2DS2-VASc score was 3 in all cohorts and the median HAS-BLED score was 2 in all cohorts. There was a statistically significant increase in the use of anticoagulant therapy from C2 to C5 (C2 54.7%, C3 60.3%, C4 73.1%, C5 73.9%; P value for trend <0.0001). The increase in the use of anticoagulant was mainly in patients with CHA2DS2-VASc ≥2. The use of vitamin K antagonists (VKAs)±antiplatelet (AP) drugs decreased from C2 to C5 (C2 53.3%, C3 52.1%, C4 50.3%, C5 30.6%), while the use of non-vitamin K antagonist oral anticoagulants (NOACs)±AP increased (C2 1.3%, C3 8.0%, C4 22.7%, C5 43.3%). The use of AP only decreased (C2 36.4%, C3 25.5%, C4 11.9%, C5 10.5%), as did the combination therapy of VKA+AP (C2 13.6%, C3 11.0%, C4 9.6%, C5 5.8%). There has been a progressive increase in the proportion of patients newly diagnosed with AF receiving guideline-recommended therapy in the UK, potentially driven by the availability of NOACs. NCT01090362; Pre-results.


Trauma in pregnancy: assessment and treatment.
Women between the ages of 10 and 50 year-old have the potential for pregnancy; therefore this condition must be taken into consideration when a woman is examined in the Emergency Room after sustaining a traumatic event. Pregnancy produces significant physiologic and anatomic changes in every system of the female body. The evaluation of the traumatized pregnant patient, the approach, and the interpretation of the diagnostic tests results must be accompanied by the full knowledge of all changes that take place during pregnancy. In the same context, although the physician treating a pregnant trauma victim must remember that there are two patients, the treatment priorities are the same as for the non-pregnant trauma patient. The best initial treatment for the fetus is the optimum resuscitation of the mother. A thorough exam should take place to discover unique conditions that might be present in any pregnant patient such as blunt or penetrating injury to the uterus, placental abruption, amniotic fluid embolism, isoimmunization, and premature rupture of membranes. The obstetrician should be present at all times and be considered a part of the trauma team in the evaluation and treatment of a pregnant trauma patient.


Fit to Study: Reflections on designing and implementing a large-scale randomized controlled trial in secondary schools.
The randomised controlled trial (RCT) design is increasingly common among studies seeking good-quality evidence to advance educational neuroscience, but conducting RCTs in schools is challenging. Fit to Study, one of six such trials funded by the Education Endowment Foundation and Wellcome Trust, tested an intervention to increase vigorous physical activity during PE lessons on maths attainment among pupils aged 12-13. This review of designing and conducting an RCT in 104 schools is intended as a resource on which researchers might draw for future studies. We consider intervention design and delivery; recruitment, retention, trial management, data collection and analysis including ethical considerations and working with evaluators. Teacher training, intervention delivery and data collection during large-scale RCTs require a flexible approach appropriate to educational settings, which in turn entails planning and resources. Simple interventions, with few outcome measures and minimal missing data, are preferable to more complex designs.


Psychotropic use and associated neuropsychiatric symptoms among patients with dementia in the USA.
To determine the national prevalence of psychotropic use and association with neuropsychiatric symptoms among patients with dementia. Participants diagnosed with dementia (n = 414) in the Aging, Demographics, and Memory Study, a nationally representative survey of US adults >70 years old. Diagnosis was based on in-person clinical assessment and informant interview. Information collected included demographics, place of residence, 10-item Neuropsychiatric Inventory (NPI), and prescribed medications (antipsychotic, sedative-hypnotic, antidepressant, mood stabilizer). Of 414 participants with dementia, 41.4% were prescribed a psychotropic medication, including 84.0% of nursing home residents and 28.6% of community-dwellers. Of participants, 23.5% were prescribed an antidepressant. Compared with the total NPI score of those on no medication (4.5), those on antipsychotics and those on sedative-hypnotics had much higher scores (respectively: 12.6, p < 0.001; 11.8, p = 0.03), although those antidepressants did not (6.9, p = 0.15). A larger proportion of patients on antipsychotics exhibited psychosis and agitation compared with those on no medication, while those on antidepressants exhibited more depressive symptoms. In multivariable logistic regression that included dementia severity and nursing home residence, nursing home residence was the characteristic most strongly associated with psychotropic use (odds ratio ranging from 8.96 [p < 0.001] for antipsychotics to 15.59 [p < 0.001] for sedative-hypnotics). More intense psychotic symptoms and agitation were associated with antipsychotic use; more intense anxiety and agitation were associated with sedative-hypnotic use. More intense depression and apathy were not associated with antidepressant use. In this nationally representative sample, 41.4% of patients were taking psychotropic medication. While associated with neuropsychiatric symptoms, nursing home residence was most strongly tied to use. Copyright © 2016 John Wiley & Sons, Ltd.


Mutations of the p53 gene in oral squamous-cell carcinomas from Sudanese dippers of nitrosamine-rich toombak and non-snuff-dippers from the Sudan and Scandinavia.
Using PCR-SSCP/DNA sequencing methods, we analyzed 14 oral squamous-cell carcinomas (OSCCs) and 8 pre-malignant oral lesions from different Sudanese patients for prevalence of mutations in exons 5 to 9 of the p53 gene in relation to toombak-dipping status. OSCCs (14 from Sudan, 28 from Scandinavia), and 3 pre-malignant oral lesions from Sudanese non-dippers were used as controls. A statistically significant increased incidence in mutations of the p53 gene was found in OSCCs from toombak dippers (93%; 13/14), as compared with those from non-dippers in Sudan (57%; 8/14) and in Scandinavia (61%; 17/28) respectively. In OSCCs from dippers, mutations were found in exons 5 to 9, while in those from non-dippers they were found in exons 5, 7, 8, 9, and no mutations were found in exon 8 in any of the OSCCs from Sudan. Certain types of mutations, however, were similar with respect to exposure to toombak. OSCCs from dippers showed 15 transversions, 9 transitions, 3 insertions and one deletion, compared with 7 transversions, 2 transitions and one deletion found in OSCCs from Sudanese non-dippers, and 9 transversions, 17 transitions and 2 insertions found in those from non-dippers in Scandinavia. No mutations were found in any of the non-malignant oral lesions in relation to dipping or non-dipping status. These findings suggest that (i) the use of toombak plays a significant role in induction of increased p53 gene mutations, (ii) mutations observed were similar to those induced by tobacco-specific N-nitrosamines (TSNAs) in experimental animal models and those already reported in toombak dippers, (iii) types of mutations associated with TSNAs were similar in the exposed and the control groups, (iv) a novel mutation in exon 6 was found in the OSCCs from toombak dippers, (v) the p53 exons 5 (codon 130), 6 (codons 190, 216) and 7 (codons 229, 249, 252) mutations are probable hot spots for toombak-related OSCCs. Further studies are necessary to validate the increased incidence and exon locations of the p53-gene mutations as a biomarker of malignant transformation in populations in which the oral use of tobacco is habitual.


Ordering for embedded coding of wavelet image data based on arbitrary scalar quantization schemes.
Many modern wavelet quantization schemes specify wavelet coefficient step sizes as continuous functions of an input step-size selection criterion; rate control is achieved by selecting an appropriate set of step sizes. In embedded wavelet coders, however, rate control is achieved simply by truncating the coded bit stream at the desired rate. The order in which wavelet data are coded implicitly controls quantization step sizes applied to create the reconstructed image. Since these step sizes are effectively discontinuous, piecewise-constant functions of rate, this paper examines the problem of designing a coding order for such a coder, guided by a quantization scheme where step sizes evolve continuously with rate. In particular, it formulates an optimization problem that minimizes the average relative difference between the piecewise-constant implicit step sizes associated with a layered coding strategy and the smooth step sizes given by a quantization scheme. The solution to this problem implies a coding order. Elegant, near-optimal solutions are presented to optimize step sizes over a variety of regions of rates, either continuous or discrete. This method can be used to create layers of coded data using any scalar quantization scheme combined with any wavelet bit-plane coder. It is illustrated using a variety of state-of-the-art coders and quantization schemes. In addition, the proposed method is verified with objective and subjective testing.


Coagulation testing and management in liver disease patients.
The present article aims to provide clinicians with an overview of coagulation testing in individuals with liver disease, to discuss available procoagulants and the rationale for their use, and to provide management strategies in a variety of common clinical scenarios. Clinicians and researchers are gaining an increased understanding of the shortfalls of assessing bleeding risk using traditional tests of coagulation. The use of global tests of clot formation, including viscoelastic testing and thrombin generation analysis, continues to evolve and guide the management of these patients. Abnormal coagulation testing in individuals with cirrhosis leads to a variety of difficult clinical scenarios that can be challenging for practitioners. With advanced liver disease, changes in the traditional tests of hemostasis such as the international normalized ratio reflect decreased synthesis of procoagulant factors but do not capture concomitant decreases in anticoagulant factors. In this setting, transfusion thresholds targeting platelet and fibrinogen goals may provide an effective strategy to optimize clot formation. Global tests of clot formation provide practical information to clinicians and can help guide decision making, although optimal target levels have not been validated.


A comparative study of magnetization dynamics in dinuclear dysprosium complexes featuring bridging chloride or trifluoromethanesulfonate ligands.
We utilized a rigid ligand platform PyCp22- (PyCp22- = [2,6-(CH2C5H3)2C5H3N]2-) to isolate dinuclear Dy3+ complexes [(PyCp2)Dy-(μ-O2SOCF3)]2 (1) and [(PyCp2)Dy-(μ-Cl)]2 (3) as well as the mononuclear complex (PyCp2)Dy(OSO2CF3)(thf) (2). Compounds 1 and 2 are the first examples of organometallic Dy3+ complexes featuring triflate binding. The isolation of compounds 1 and 3 allows us to comparatively evaluate the effects of the bridging anions on the magnetization dynamics of the dinuclear systems. Our investigations show that although the exchange coupling interactions differ for 1 and 3, the dynamic magnetic properties are dominated by relaxation via the first excited state Kramers doublet of the individual Dy sites. Compounds 1 and 3 exhibit barriers to magnetization reversal (Ueff = 49 cm-1) that can be favorably compared to those of the previously reported examples of [Cp2Dy(μ-Cl)]2 (Ueff = 26 cm-1) and [Cp2Dy(thf)(μ-Cl)]2 (Ueff = 34 cm-1).


Abrogation of the twin arginine transport system in Salmonella enterica serovar Typhimurium leads to colonization defects during infection.
TatC (STM3975) is a highly conserved component of the Twin Arginine Transport (Tat) systems that is required for transport of folded proteins across the inner membrane in gram-negative bacteria. We previously identified a ΔtatC mutant as defective in competitive infections with wild type ATCC14028 during systemic infection of Salmonella-susceptible BALB/c mice. Here we confirm these results and show that the ΔtatC mutant is internalized poorly by cultured J774-A.1 mouse macrophages a phenotype that may be related to the systemic infection defect. This mutant is also defective for short-term intestinal and systemic colonization after oral infection of BALB/c mice and is shed in reduced numbers in feces from orally infected Salmonella-resistant (CBA/J) mice. We show that the ΔtatC mutant is highly sensitive to bile acids perhaps resulting in the defect in intestinal infection that we observe. Finally, the ΔtatC mutant has an unusual combination of motility phenotypes in Salmonella; it is severely defective for swimming motility but is able to swarm well. The ΔtatC mutant has a lower amount of flagellin on the bacterial surface during swimming motility but normal levels under swarming conditions.


Housing choices and care home design for people with dementia.
This article reviews the current state of housing for people with dementia by exploring housing choices available to this group, and identifying potential issues with design of care homes. Older people who wish to age in place are faced with the challenge of adapting their domestic environment to ensure independence, accessibility, and social connectivity. This is even more challenging for people with dementia who continue to live at home, given the risks of self-harm and getting lost. More imaginative and inclusive forms of collective housing are needed. For people with dementia, a move to a new environment is often a stressful experience that causes shock, withdrawal, and anger. Hence, more research is needed to develop more fitting long-term housing options for people with dementia. This article presents a brief review on housing choices and housing design for people with dementia. Interviews with managers of 22 care homes were conducted to explore housing choices and design issues. Results show that the main housing choices available to people with dementia offer different levels of care. The choice of care homes relates to the atmosphere of a home as some occupants favor a homely or relaxing environment and others prefer dynamic settings. A combination of appropriate level of care, a good atmosphere, and design quality within the care home are elements that lead to a more enabling environment. Design of a successful caring environment also requires appropriate care and a positive therapeutic and domestic-looking environment.


Mechanical Forces and Their Effect on the Ribosome and Protein Translation Machinery.
Mechanical forces acting on biological systems, at both the macroscopic and microscopic levels, play an important part in shaping cellular phenotypes. There is a growing realization that biomolecules that respond to force directly applied to them, or via mechano-sensitive signalling pathways, can produce profound changes to not only transcriptional pathways, but also in protein translation. Forces naturally occurring at the molecular level can impact the rate at which the bacterial ribosome translates messenger RNA (mRNA) transcripts and influence processes such as co-translational folding of a nascent protein as it exits the ribosome. In eukaryotes, force can also be transduced at the cellular level by the cytoskeleton, the cell's internal filamentous network. The cytoskeleton closely associates with components of the translational machinery such as ribosomes and elongation factors and, as such, is a crucial determinant of localized protein translation. In this review we will give (1) a brief overview of protein translation in bacteria and eukaryotes and then discuss (2) how mechanical forces are directly involved with ribosomes during active protein synthesis and (3) how eukaryotic ribosomes and other protein translation machinery intimately associates with the mechanosensitive cytoskeleton network.


YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.
The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.


Diabetes Increases Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study With Propensity Score Analysis.
Whether diabetes mellitus (DM) increases risk of gastric cancer (GC) remains controversial because of inadequate adjustments for important risk factors, including Helicobacter pylori (HP) infection status, concomitant medication use, and cancer site. We investigated whether type 2 DM increased risk of GC in patients after they received treatment for HP infection. This was a territory-wide cohort study of patients aged ≥45 years who had received clarithromycin-based triple therapy for HP infection between 2003 and 2012 in Hong Kong. Data were retrieved from a public electronic health database. Observation started from receipt of therapy for HP infection to GC diagnosis, death, or the end of the study (December 2015). Exclusion criteria included type 1 DM, GC diagnosed within the 1st year of HP therapy, prior GC or gastrectomy, and retreatment for HP infection. The adjusted hazard ratio (aHR) of GC with type 2 DM was calculated by using a Cox model that adjusted for 20 covariates (age, sex, comorbidities, and medications) through propensity score regression. During a median follow-up of 7.1 years (interquartile range 4.8-9.3 years), 153 of 46,460 patients (0.33%) developed GC at a median age of 72.4 years. Type 2 DM was associated with an increased risk of GC (aHR 1.73 [95% CI 1.08-2.79]). Stratified analysis showed an increase in risk for cardia cancer only (aHR 3.40 [95% CI 1.45-7.97]) and in those with suboptimal DM control (time-weighted mean HbA1c ≥6.0% [42 mmol/mol]; aHR 1.68 [95% CI 1.07-2.63]). Type 2 DM is associated with an increased risk of GC among patients in whom HP was eradicated, in particular gastric cardia cancer and in those with suboptimal DM control.


Cytochrome P450 2B6 genetic variants are associated with plasma nevirapine levels and clinical response in HIV-1 infected Kenyan women: a prospective cohort study.
Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women. Study subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression. Women with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 μg/mL) compared to those with heterozygous 516GT (9.18 μg/mL; n=25) and wild- type 516GG (7.95 μg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 μg/mL), compared to women with the homozygous 983TT (8.35 μg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/μL, 95% CI, 27.3-211.5 cells/μL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/μL, 95% CI, 3.9-133.4 cells/μL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity. CYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.


Prevalence and Causes of Visual Impairment and Blindness in Three Ecological Regions of Nepal.
Visual impairment and blindness are significant public health issues worldwide. The objective of this study was to estimate the prevalence and causes of moderate to severe visual impairment (MSVI) and blindness in people aged 15 years and above across three ecological regions of Nepal. A comparative cross-sectional study was conducted in one district in each of the three ecological regions of Nepal. Number of participants from each region was distributed as per the prevalence findings of pilot study, with 2815 participants enrolled in Dolakha, 1509 in Dhading and 910 in Sarlahi. Intensive training was provided to health workers on how to conduct door-to-door enumeration, visual acuity testing and referral when indicated for comprehensive ocular examination by technicians and ophthalmologists to diagnose and treat ocular morbidities. Collected data were analyzed using standard software. For categorical data, frequency, percentage and 95% CI were calculated and statistical tests were done using Chi-square/Fisher exact test. Altogether 5234 participants were enrolled in the study (participation rate 96.4%). The overall prevalence of MSVI was 9.5% (495). It was 4.7% (133) in the mountainous region, 11.2% (169) in the Hill and 21.2% (193) in the Tarai. In those aged 15-49 years, MSVI prevalence was 1.5% (52) and 25.1% (433) in ≥50 years. The overall prevalence of blindness was 0.9% (47). It was 0.2% (6) in 15-49 and 2.3% (41) in ≥50 age groups. More than 95% visual impairment and blindness were due to cataract and uncorrected refractive error. Cataract was the leading cause of visual impairment and blindness (290, 53.5%), followed by uncorrected refractive error. The prevalence of visual impairment and blindness varied significantly with age, ethnicity and locality. The management of uncorrected refractive error and operable cataract would reduce nine in ten cases of moderate to severe visual impairment and blindness.


Transfer learning improves supervised image segmentation across imaging protocols.
The variation between images obtained with different scanners or different imaging protocols presents a major challenge in automatic segmentation of biomedical images. This variation especially hampers the application of otherwise successful supervised-learning techniques which, in order to perform well, often require a large amount of labeled training data that is exactly representative of the target data. We therefore propose to use transfer learning for image segmentation. Transfer-learning techniques can cope with differences in distributions between training and target data, and therefore may improve performance over supervised learning for segmentation across scanners and scan protocols. We present four transfer classifiers that can train a classification scheme with only a small amount of representative training data, in addition to a larger amount of other training data with slightly different characteristics. The performance of the four transfer classifiers was compared to that of standard supervised classification on two magnetic resonance imaging brain-segmentation tasks with multi-site data: white matter, gray matter, and cerebrospinal fluid segmentation; and white-matter-/MS-lesion segmentation. The experiments showed that when there is only a small amount of representative training data available, transfer learning can greatly outperform common supervised-learning approaches, minimizing classification errors by up to 60%.


Traumatic focal pancreatitis with retro-duodenal hematoma: a rare cause of combined biliary and gastric outlet obstruction.
Focal post-traumatic acute pancreatitis causing combined duodenal and biliary obstruction is extremely rare. A 16-year-old boy presented with acute upper abdominal pain which was clinically and biochemically consistent with mild acute pancreatitis. There was no etiological factor identified initially, although a history of blunt abdominal trauma was later discovered. He soon developed features of gastric outlet obstruction and obstructive jaundice over 48 hours. A CT scan showed a retroduodenal mass causing compression of both the duodenum and bile duct. At exploration, this was found to be a walled off hematoma. There was evidence of focal pancreatitis in the head of pancreas. Evacuation of the hematoma cured the gastric outlet and biliary obstruction. The triad of pancreatitis, gastric outlet and biliary obstruction along with a mass lesion on cross sectional imaging in young adults should raise the suspicion of a hematoma as a probable cause.


Modulation of immune cell function, IDO expression and kynurenine production by the quorum sensor 2-heptyl-3-hydroxy-4-quinolone (PQS).
Many invasive micro-organisms produce 'quorum sensor' molecules which regulate colony expansion and may modulate host immune responses. We have examined the ability of Pseudomonas Quorum Sensor (PQS) to influence cytokine expression under conditions of inflammatory stress. The administration of PQS in vivo to mice with collagen-induced arthritis (CIA) increased the severity of disease. Blood and inflamed paws from treated mice had fewer regulatory T cells (Tregs) but normal numbers of Th17 cells. However, PQS (1μM) treatment of antigen-stimulated lymph node cells from collagen-immunised mice in vitro inhibited the differentiation of CD4+IFNγ+ cells, with less effect on CD4+IL-17+ cells and no change in CD4+FoxP3+Tregs. PQS also inhibited T cell activation by anti-CD3/anti-CD28 antibodies. PQS reduced murine macrophage polarisation and inhibited expression of IL1B and IL6 genes in murine macrophages and human THP-1 cells. In human monocyte-derived macrophages, IDO1 gene, protein and enzyme activity were all inhibited by exposure to PQS. TNF gene expression was inhibited in THP-1 cells but not murine macrophages, while LPS-induced TNF protein release was increased by high PQS concentrations. PQS is known to have iron scavenging activity and its suppression of cytokine release was abrogated by iron supplementation. Unexpectedly, PQS decreased the expression of indoleamine-2, 3-dioxygenase genes (IDO1 and IDO2), IDO1 protein expression and enzyme activity in mouse and human macrophages. This is consistent with evidence that IDO1 inhibition or deletion exacerbates arthritis, while kynurenine reduces its severity. It is suggested that the inhibition of IDO1 and cytokine expression may contribute to the quorum sensor and invasive actions of PQS.


[EVALUATION OF THE BODY ADIPOSITY INDEX IN PREDICTING PERCENTAGE BODY FAT AMONG COLOMBIAN ADULTS].
the body adiposity index (BAI) is a new simplistic method for predicting body fat percentage (BF%) via a simple equation of hip circumference to height. Up to now, few studies have evaluated the performance of BAI in determining excess fat in Colombians. The aim of this study was to evaluate the usefulness of BAI as a predictor of body fat in among Colombian adults. cross-sectional study carried out in a sample of 204 male belonging to the education sector from Bogotá, Colombia. BAI was calculated based on the equation reported in the Bergman et al. %BF determined by tetrapolar bioimpedance analysis (BIA) was used as the reference measure of adiposity. Bland-Altman analysis was used to assess the agreement between the two methods: BAI and BIA. Associations between anthropometric measures of adiposity were investigated by Pearson correlation analysis. in general pupulation, the BAI overestimates %BF (mean difference: 12.5 % [95%CI = -4.04 % to -21.02 %]), mainly at lower levels of adiposity (mean difference: 10.2 ± 3.3). Significant correlations were found between BAI and all measurements, being the strongest-moderate correlation with %BF (r = 0.777, p < 0.001), waist to height ratio (r = 0.557, p < 0.001) and BMI (r = 0.480, p < 0.001). the results of this investigation indicate that BAI results in large individual errors when predicting BF% among Colombian adults and has a tendency to provide overestimated values as BF% decreases. Therefore, this method can be a useful tool to predict %BF in Colombian adults, although it has some limitations.


Risk factors associated with sustained circulation of six zoonotic arboviruses: a systematic review for selection of surveillance sites in non-endemic areas.
Arboviruses represent a significant burden to public health and local economies due to their ability to cause unpredictable and widespread epidemics. To maximize early detection of arbovirus emergence in non-endemic areas, surveillance efforts should target areas where circulation is most likely. However, identifying such hotspots of potential emergence is a major challenge. The ecological conditions leading to arbovirus outbreaks are shaped by complex interactions between the virus, its vertebrate hosts, arthropod vector, and abiotic environment that are often poorly understood. Here, we systematically review the ecological risk factors associated with the circulation of six arboviruses that are of considerable concern to northwestern Europe. These include three mosquito-borne viruses (Japanese encephalitis virus, West Nile virus, Rift Valley fever virus) and three tick-borne viruses (Crimean-Congo hemorrhagic fever virus, tick-borne encephalitis virus, and louping-ill virus). We consider both intrinsic (e.g. vector and reservoir host competence) and extrinsic (e.g. temperature, precipitation, host densities, land use) risk factors, identify current knowledge gaps, and discuss future directions. Our systematic review provides baseline information for the identification of regions and habitats that have suitable ecological conditions for endemic circulation, and therefore may be used to target early warning surveillance programs aimed at detecting multi-virus and/or arbovirus emergence.


Assessing factors associated with changes in the numbers of birds visiting gardens in winter: Are predators partly to blame?
The factors governing the recent declines observed in many songbirds have received much research interest, in particular whether increases of avian predators have had a negative effect on any of their prey species. In addition, further discussion has centered on whether or not the choice of model formulation has an effect on model inference. The study goal was to evaluate changes in the number of 10 songbird species in relation to a suite of environmental covariates, testing for any evidence in support of a predator effect using multiple model formulations to check for consistency in the results. We compare two different approaches to the analysis of long-term garden bird monitoring data. The first approach models change in the prey species between 1970 and 2005 as a function of environmental covariates, including the abundance of an avian predator, while the second uses a change-change approach. Significant negative relationships were found between Eurasian Sparrowhawk Accipiter nisus and three of the 10 species analyzed, namely house Sparrow Passer domesticus, starling Sturnus vulgaris, and blue tit Cyanistes caeruleus. The results were consistent under both modeling approaches. It is not clear if this is a direct negative impact on the overall populations of these species or a behavioral response of the prey species to avoid feeding stations frequented by Sparrowhawks (which may in turn have population consequences, by reducing available resources). The species showing evidence of negative effects of Sparrowhawks were three of the four species most at risk to Sparrowhawk predation according to their prevalence in the predator's diet. The associations could be causal in nature, although in practical terms the reduction in the rate of change in numbers visiting gardens accredited to Sparrowhawks is relatively small, and so unlikely to be the main driver of observed population declines.


Evidence for Multi-Organ Infection During Experimental Meningococcal Sepsis due to ST-11 Isolates in Human Transferrin-Transgenic Mice.
The description of invasive meningococcal disease that is provoked by Neisseria meningitidis (Nm) is frequently restricted to meningitis. However, a wide panel of clinical presentations can be encountered including severe forms with intense inflammatory reaction leading to multi-organ failure. Several human factors are involved in the development of invasive infections such as transferrin, factor H or CEACAM1. In this study, we used an experimental meningococcal infection in transgenic mice expressing the human transferrin to show multi-organ infection. Mice were infected by an intraperitoneal injection of bacterial suspension (1.5 × 107 colony-forming unit/mouse) of a bioluminescent serogroup C strain belonging to the clonal complex ST-11. Dynamic imaging and histological analysis were performed. The results showed invasion of tissues by Nm with bacteria observed, outside blood vessels, in the kidneys, the heart and the brain as well as skin involvement. These data further support the systemic aspect of invasive meningococcal disease with involvement of several organs including skin as in humans. Thus, our model can be used to study severe forms of meningococcal invasive infections with multi-organ failure.


Implementation of a Low-Cost Quality Improvement Intervention Increases Adherence to Cancer Screening Guidelines and Reduces Healthcare Costs at a University Medical Center.
Adherence to US Preventative Services Task Force (USPSTF) cancer screening guidelines remains considerably lower than the recommendation of the Healthy People 2020 initiative. Patient populations recommended for screening are not screened at an appropriate rate, and populations not recommended for screening are inappropriately screened. Closer adherence to guidelines should improve outcomes and reduce costs, estimated to reach $158 billion/year by 2020. We evaluated whether a use of low-cost educational health maintenance (HM) card by medical residents at a university hospital could impact education and adherence to updated cancer screening guidelines. We also analyzed savings to the healthcare system. Adherence to cervical, breast, and colorectal cancer screening guidelines, defined as percentage that was screened (or not screened) in accordance with the USPSTF guidelines, in clinic visits from December 2012 (n = 336) was compared to those from December 2013 (n = 306) after a quality improvement intervention. Post-intervention, adherence to screening guidelines increased by 40.8% (p < 0.01) for cervical, 33.2% (p < 0.01) for breast, and 20.5% (p < 0.01) for colorectal cancer in average-risk patients. Inappropriate screening was reduced by 26.8% (p < 0.01) for cervical and 32.8% (p < 0.01) for breast cancer. A non-significant 1.1% decrease (p = 0.829) was observed for colorectal cancer. The annual potential savings from avoiding inappropriate screenings were $998,316 (95% CI; $644,484-$1,352,148). We showed a significant absolute increase in USPSTF knowledge of 28.3% irrespective of the house staff level that remained high at 2 years from the educational intervention. The low-cost HM card increased appropriate knowledgeable cancer screening adherence while reducing unnecessary testing and producing substantial savings to the healthcare system.


Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors.
Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and familial (n = 121) prostate cancer patients and population controls (n = 923). We identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene, T201M, with a mild significant association with prostate cancer [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis revealed that this risk was most apparent in patients with organ-confined (T(1)-T(2)) and low-grade (WHO grade 1) tumors (OR, 5.42; 95% CI, 2.33-12.6; P < 0.0001). In contrast, CYP17A1 -34T>C alteration was associated with moderate to poorly differentiated (WHO grade 2-3) organ-confined disease (OR, 1.42; 95% CI, 1.09-1.83; P = 0.007). We also tested a multigenic model of prostate cancer risk by calculating the joint effect of CYP19A1 T201M with five other common SNPs. Individuals carrying both the CYP19A1 and KLK3 -252A>G variant alleles had a significantly increased risk for prostate cancer (OR, 2.87; 95% CI, 1.10-7.49; P = 0.03). In conclusion, our results suggest that several SNPs along the androgen pathway, especially in CYP19A1 and CYP17A1, may influence prostate cancer development and progression. These genes may have different contributions to distinct clinical subsets as well as combinatorial effects in others illustrating that profiling and joint analysis of several genes along each pathway may be needed to understand genetic contributions to prostate cancer etiology.


Concentration-dependent effects of prednisolone on lymphocyte subsets and mixed lymphocyte culture in humans.
In a previous study the feasibility of pharmacokinetic-pharmacodynamic modeling for a quantitative description of the lymphocytopenic effect of prednisolone was demonstrated. We now applied this technique to compare the lymphocytopenia of T-lymphocyte subsets, namely CD8 and CD4. The finding of similar rate constants for the delay of the effect on different T-lymphocyte categories supports the explanation of this delay on the basis of pharmacokinetics rather than cellkinetics. The time course of the responsiveness of remaining lymphocytes in mixed lymphocyte culture after prednisolone administration could be described with the same model as the lymphocytopenia. The concurrence of both effects suggests that total lymphocyte counts, if considered intraindividually, could be used as a measure for monitoring the indirect immunosuppressive effect of prednisolone. The inhibitory effect on mixed lymphocyte culture of plasma from subjects who received prednisolone was directly related with the prednisolone concentrations in plasma. Just as for the indirect effect, a threshold concentration could be observed in the concerning concentration-effect relation. This is attributed to the decrease of endogenous hydrocortisone levels under the influence of prednisolone. Possible consequences of our results and those from related studies for the use of prednisolone as an immunosuppressive drug are discussed.


Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells.
Circulating tumor cells (CTCs) are shed into the bloodstream from primary and metastatic tumor deposits. Their isolation and analysis hold great promise for the early detection of invasive cancer and the management of advanced disease, but technological hurdles have limited their broad clinical utility. We describe an inertial focusing-enhanced microfluidic CTC capture platform, termed "CTC-iChip," that is capable of sorting rare CTCs from whole blood at 10(7) cells/s. Most importantly, the iChip is capable of isolating CTCs using strategies that are either dependent or independent of tumor membrane epitopes, and thus applicable to virtually all cancers. We specifically demonstrate the use of the iChip in an expanded set of both epithelial and nonepithelial cancers including lung, prostate, pancreas, breast, and melanoma. The sorting of CTCs as unfixed cells in solution allows for the application of high-quality clinically standardized morphological and immunohistochemical analyses, as well as RNA-based single-cell molecular characterization. The combination of an unbiased, broadly applicable, high-throughput, and automatable rare cell sorting technology with generally accepted molecular assays and cytology standards will enable the integration of CTC-based diagnostics into the clinical management of cancer.


Evolution of condensin and cohesin complexes driven by replacement of Kite by Hawk proteins.
Mitotic chromosome condensation, sister chromatid cohesion, and higher order folding of interphase chromatin are mediated by condensin and cohesin, eukaryotic members of the SMC (structural maintenance of chromosomes)-kleisin protein family. Other members facilitate chromosome segregation in bacteria [1]. A hallmark of these complexes is the binding of the two ends of a kleisin subunit to the apices of V-shaped Smc dimers, creating a tripartite ring capable of entrapping DNA (Figure 1A). In addition to creating rings, kleisins recruit regulatory subunits. One family of regulators, namely Kite dimers (Kleisin interacting winged-helix tandem elements), interact with Smc-kleisin rings from bacteria, archaea and the eukaryotic Smc5-6 complex, but not with either condensin or cohesin [2]. These instead possess proteins containing HEAT (Huntingtin/EF3/PP2A/Tor1) repeat domains whose origin and distribution have not yet been characterized. Using a combination of profile Hidden Markov Model (HMM)-based homology searches, network analysis and structural alignments, we identify a common origin for these regulators, for which we propose the name Hawks, i.e. HEAT proteins associated with kleisins.


Transtympanic Injections of N-acetylcysteine and Dexamethasone for Prevention of Cisplatin-Induced Ototoxicity: Double Blind Randomized Clinical Trial.
Cisplatin is a potent chemotherapeutic agent that is used against a variety of tumors. The most common side effect of cisplatin is ototoxicity. This dose-related hearing impairment is high frequency, bilateral, and permanent. Unfortunately, there is no prophylactic protocol, and, in current clinical practice, the treatment of cancer with cisplatin is interrupted when ototoxicity develops or the resulting hearing impairment is tolerated as an acceptable side effect of cancer treatment. The aim of this study is to compare transtympanic injections of N-acetylcysteine and dexamethasone (both of which have shown substantial otoprotective activity) for the prevention of cisplatin-induced ototoxicity. A double blind randomised clinical trial study of 60 cisplatin-treated patients was performed in Shahid Sadoughi Hospital in 2016-2017. Transtympanic injection of N-acetylcysteine (10%) and dexamethasone was performed. Hearing acuity was evaluated by an audiologist blinded to the treated ears before each cycle with pure tone audiometry (PTA) and six months later. Altogether, 114 transtympanic infusions were performed (57 in each group). The data were analyzed by the Fisher test and chi-squared. In the ears with N-acetylcysteine, no significant changes in auditory thresholds were recorded. In the ears with dexamethasone, cisplatin induced a significant decrease of auditory thresholds at the 8000 Hz frequency band (P = 0.001). Transtympanic injections of N-acetylcysteineas a safe and inexpensive antioxidant agent seem to be an effective otoprotective strategy for the prevention of cisplatin-induced ototoxicity and for increasing the quality of life, especially in children.


A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas.
OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.


Lymphocyte subpopulations in premature infants: an observational study.
The infant's immune system evolves over the first months and years of life. Strong correlation exists between lymphocyte count, lymphocyte subpopulations and gestational age at birth. Associations with antenatal and postnatal steroid treatment, infection and chronic lung disease have also been described. Few published studies report the effect of increasing postnatal age (PNA) and comorbidities on lymphocyte subpopulations in premature infants beyond the first 4 months of life. This study aimed to describe changes in lymphocyte subpopulations in preterm infants up to 13 months PNA. Premature infants (23-34 weeks completed gestation) from five centres had lymphocyte subpopulations measured at 2, 5 or 7, 12 and 13 months PNA alongside their vaccine responses in a vaccination trial. 393 blood samples from 151 babies were analysed. There was an increase in absolute numbers of total lymphocytes (median cell count 6.21×109/L at 13 months compared with 4.9×109/L at 2 months PNA) and CD3+, CD4+, CD8+, natural killer and B cells with increasing age. At 2 months PNA, there was a positive correlation between gestation and CD3+ and CD4+ counts (r=0.32 and 0.46, respectively) and proportions (r=0.22 and 0.41, respectively), and CD4+:CD8+ ratios (r=0.57), but a negative correlation with CD8+ proportions (r=-0.32). This longitudinal study describes the distribution of lymphocyte subpopulations in premature infants and provides reference ranges for the major lymphocyte subsets to help guide clinicians when assessing premature infants for immunodeficiency in the first year of life. EudraCT 2007-007535-23.


Toxin genes and cytotoxicity levels detected in Bacillus cereus isolates collected from cooked food products delivered by Swiss Army catering facilities.
Heated food is known to be often contaminated with B. cereus, leading to cases of diarrhoeal or emetic diseases. Battalion kitchens or army catering facilities present a food safety risk, as temperature abuse and long storage time can result in serious public health problems affecting a high number of served people. In contrast to civil catering facilities, no microbiological monitoring systems are currently implemented in Swiss military kitchens. In this study toxin gene profiles and cytotoxicity levels of 21 isolates of B. cereus originating from six different food categories were determined. Nearly all isolates (95%) harbored the nhe gene, whereas no hbl could be detected. Seven isolates displayed the cytK2 gene and one cereulide-producer was isolated out of vegetables. While most isolates displayed low cytotoxicity, highly cytotoxic strains were detected, with three isolates even exceeding the cytotoxicity level of the reference strain for high-level toxin production, underpinning that cytotoxicity cannot be deduced only from presence or absence of toxin genes. These findings further underline the importance of rapid cooling of foods or maintenance over 65°C before serving. This is especially important in mass catering facilities, such as military kitchens, in which food is often prepared a long time in advance.


3-D vascular skeleton extraction and decomposition.
We introduce a novel vascular skeleton extraction and decomposition technique for computer-assisted diagnosis and analysis. We start by addressing the problem of vascular decomposition as a cluster optimization problem and present a methodology for weighted convex approximations. Decomposed vessel structures are then grouped using the vessel skeleton, extracted using a Laplace-based operator. The method is validated using presegmented sections of vasculature archived for 98 aneurysms in 112 patients. We test first for vascular decomposition and next for vessel skeleton extraction. The proposed method produced promising results with an estimated 80.5% of the vessel sections correctly decomposed and 92.9% of the vessel sections having the correct number of skeletal branches, identified by a clinical radiological expert. Next, the method was validated on longitudinal study data from n = 4 subjects, where vascular skeleton extraction and decomposition was performed. Volumetric and surface area comparisons were made between expert segmented sections and the proposed approach on sections containing aneurysms. Results suggest that the method is able to detect changes in aneurysm volumes and surface areas close to that segmented by an expert.


A review on boiling heat transfer enhancement with nanofluids.
There has been increasing interest of late in nanofluid boiling and its use in heat transfer enhancement. This article covers recent advances in the last decade by researchers in both pool boiling and convective boiling applications, with nanofluids as the working fluid. The available data in the literature is reviewed in terms of enhancements, and degradations in the nucleate boiling heat transfer and critical heat flux. Conflicting data have been presented in the literature on the effect that nanofluids have on the boiling heat-transfer coefficient; however, almost all researchers have noted an enhancement in the critical heat flux during nanofluid boiling. Several researchers have observed nanoparticle deposition at the heater surface, which they have related back to the critical heat flux enhancement.


Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease.
We conducted a retrospective study in 229 patients to determine the prevalence of hepatitis C virus (HCV) according to the type of liver disease and also the serum hepatitis B virus (HBV) status. There were 55 cases of hepatocellular carcinoma (HCC), 78 cases of alcoholic cirrhosis (AC) and 96 cases of non-cirrhotic alcohol liver disease (NCA). Half the AC and NCA groups were constituted of patients with or without serum HBV markers. The prevalence of anti-HCV antibodies in HCC (58.2%) was significantly higher than in the other groups (AC, 35.9%; NCA, 17.7%). Combining the two AC and NCA groups gave a 25.8% anti-HCV prevalence in the alcoholics. Altogether anti-HCV antibodies were more frequently present in HBV-positive than in HBV-negative patients (42.2 vs. 26.1%, p less than 0.01), although the difference was not significant when the HCC group was separately analysed. The S/N ratio of anti-HCV-positive samples varied according to the type of the disease (tumorous vs. non-tumorous) and to the serum HBV status. Indeed, 65.6% of HCC had a S/N greater than 4 compared to only 32.2 and 23.5% in AC and NCA, respectively (p less than 0.01). On the other hand more than half of the AC and NCA had a S/N less than 2, indicating possible artefacts in certain cases. The 15 HBsAg and anti-HCV-positive patients had a significantly lower mean S/N than patients displaying only antibodies against HBV, even in the HCC group.(ABSTRACT TRUNCATED AT 250 WORDS)


[Sepsis caused by Chryseobacterium indologenes in a patient with hydrocephalus].
Chryseobacterium (formerly Flavobacterium) indologenes, is a non-fermentative gram-negative bacillus which is widely found in the nature, primarily soil and water. Since it can survive in chlorine-treated municipal water supplies, and can colonize the sink basins and tap waters of the hospitals, this bacterium may be a potential infectious agent. Contamination of the medical devices containing water (respirators, intubation tubes, humidifiers, incubators for newborns, etc.) in hospital settings may lead to serious infections especially in patients with predisposing diseases, newborns and immunocompromized patients. In this report, a case of fatal C.indologenes septicemia developed in a newborn with hydrocephalus has been presented. A two-months old male infant was admitted to our hospital with the complaints of failure to suck and lethargy for five days and head enlargement. He was diagnosed as meningitis based on the clinical and laboratory findings of cerebrospinal fluid (CSF) (protein: 572 mg/dl, glucose 9.5 mg/dl, chlorine: 111 mg/dl, and presence of abundant polymorphonuclear leukocytes), and empirical antibiotic treatment (ampicillin/sulbactam and cefotaxime) had been started. Since the computerized tomography of the brain pointed out hydrocephalus, an external shunt was placed for CSF drainage on the second day of hospitalization. A total of five CSF and two blood cultures collected during the hospitalization period were inoculated into pediatric aerobic CSF and blood culture bottles (BacT/ALERT, BioMerieux, France) and incubated for 24-48 hours. The isolated bacteria from all of the cultures were identified as C.indologenes by conventional methods and BD Phoenix (Becton Dickinson, USA) system. Antibiotic susceptibility tests were performed with microdilution method according to CLSI guidelines. The isolate was found susceptible to ciprofloxacin, levofloxacin and trimethoprim/sulfamethoxazole, while it was resistant to amikacin, gentamicin, tobramycin, piperacillin, cefotaxime, ceftazidime, aztreonam, meropenem, imipenem, tetracycline, and chloramphenicol. The treatment continued with ampicillin/sulbactam and levofloxacin without removing the shunt. However, C.indologenes growth persisted in CSF and blood cultures of the patient. The general condition of the patient deteriorated on the 65. day of the hospitalization and the patient was lost due to cardiopulmonary arrest. Case reports related to isolation of C.indologenes from blood cultures are present in the literature, however, isolation of C.indologenes from central nervous system was reported previously in a single case. In conclusion, C.indologenes should be considered as opportunistic infectious agents especially in the infectious diseases that develop in immunocompromised patients with underlying disease and with foreign device implementation.


Acute respiratory infection in children from developing nations: a multi-level study.
Worldwide, acute respiratory infections (ARI) are the leading cause of death of children under 5 years of age. To assess the accomplishment of the Millennium Development Goal on under-5 mortality particularly related to ARI in developing countries, and to explore the associations between country characteristics and ARI in children under 5 taking into account child, mother and household attributes. The study included a representative sample of 354,633 children under 5 years from 40 developing nations. A multilevel analysis of data from the Demographic and Health Surveys and the World Bank was conducted. The prevalence of ARI was 13%. Country inequalities were associated with the disease - GINI index (95% CI 1.01-1.04). The country's per capita gross domestic product (GDP) (95% CI 1.00-1.01) and health expenditure (95% CI 1.01-1.01) affected the relationship between immunization and ARI, while inequalities influenced the relationship between household wealth (95% CI 0.99-0.99) and the disease. Other factors positively associated with ARI were male gender, low birthweight, working mothers and a high-risk indoor environment. Factors associated with ARI reduction were older children, immunization, breastfeeding for more than 6 months, older maternal age, maternal education and planned pregnancy. In developing countries, public health campaigns to target ARI should consider the country's macro characteristics. At country level, inequalities but not health expenditure or GDP were associated with the disease and were independent of child, family and household characteristics. The effect of immunization on reducing ARI is greater in countries with a higher GDP and health expenditure. The effect of household wealth on ARI is less in countries with fewer inequalities. Reduction of inequalities is an important measure to decrease ARI in developing countries.


Parental and home influences on adolescents' TV viewing: a mediation analysis.
To explore the association between home environmental variables and television (TV) time, and the mediating pathways underlying this association. The current study used data from the longitudinal ENDORSE study. Self-reported data was available for 1 265 adolescents (mean age of 12-15 years at baseline) on home environment (availability of a TV in the bedroom, perceived parental modelling, family rules), potential mediators (intention, attitude, perceived behavioural control, subjective norm towards TV viewing) and TV viewing time. Mediation analyses were conducted using General Estimating Equations and mediation effects were calculated as the product-of-coefficients. Significant overall positive associations were found for the presence of a TV in the bedroom and parental modelling with self-reported TV viewing. Controlling family rules showed an inverse association with reported TV time. Similarly, parental modelling and a TV in the bedroom were significantly positively associated with the Theory of Planned Behaviour variables and habit strength, while family rules showed an inverse association with these potential mediators. In turn, most potential mediators were positively associated with TV viewing. Intention, attitude and habit strength were the strongest mediators in all three associations explaining more than 55% of the overall association. Habit strength alone explained 38.2%-58.0% of the overall associations. Home and family environmental predictors of TV time among adolescents may be strongly mediated by habit strength and other personal factors. Future intervention studies should explore if changes in home and family environments indeed lead to reductions in TV time through these mediators.


Navigating the nuances of clinical sequence variant interpretation in Mendelian disease.
Understanding clinical genetic test results in the era of next-generation sequencing has become increasingly complex, necessitating clear and thorough guidelines for sequence variant interpretation. To meet this need the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for a systematic approach for sequence variant interpretation in 2015. This framework is intended to be adaptable to any Mendelian condition, promoting transparency and consistency in variant interpretation, yet its comprehensive nature yields important challenges and caveats that end users must understand. In this review, we address some of these nuances and discuss the evolving efforts to refine and adapt this framework. We also consider the added complexity of distinguishing between variant-level interpretations and case-level conclusions, particularly in the context of the large gene panel approach to clinical diagnostics.


Individual and work factors related to perceived work ability and labor force outcomes.
Perceived work ability refers to a worker's assessment of his or her ability to continue working in his or her job, given characteristics of the job along with his or her resources. Perceived work ability is a critical variable to study in the United States, given an aging workforce, trends to delay retirement, and U.S. policy considerations to delay the age at which full Social Security retirement benefits may be obtained. Based on the job demands-resources model, cognitive appraisal theory of stress, and push/pull factors related to retirement, we proposed and tested a conceptual model of antecedents and outcomes of perceived work ability using 3 independent samples of U.S. working adults. Data regarding workers' job characteristics were from self-report and Occupational Information Network measures. Results from relative importance analysis indicated that health and sense of control were consistently and most strongly related to work ability perceptions relative to other job demands and job and personal resources when perceived work ability was measured concurrently or 2 weeks later in samples with varying occupations. Job demands (along with health and sense of control) were most strongly related to work ability perceptions when perceived work ability was measured in a manufacturing worker sample 1.6 years later. Perceived work ability also predicted lagged labor force outcomes (absence, retirement, and disability leave) while controlling for other known predictors of each. Consistent indirect effects were observed from health status and sense of control to all 3 of these outcomes via perceived work ability.


Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis.
Several options exist for management of clinically localized renal masses suspicious for cancer, including active surveillance, thermal ablation and radical or partial nephrectomy. We summarize evidence on effectiveness and comparative effectiveness of these treatment approaches for patients with a renal mass suspicious for localized renal cell carcinoma. We searched MEDLINE®, Embase® and the Cochrane Central Register of Controlled Trials from January 1, 1997 through May 1, 2015. Paired investigators independently screened articles to identify controlled studies of management options or cohort studies of active surveillance, abstracted data sequentially and assessed risk of bias independently. Strength of evidence was graded by comparisons. The search identified 107 studies (majority T1, no active surveillance or thermal ablation stratified outcomes of T2 tumors). Cancer specific survival was excellent among all management strategies (median 5-year survival 95%). Local recurrence-free survival was inferior for thermal ablation with 1 treatment but reached equivalence to other modalities after multiple treatments. Overall survival rates were similar among management strategies and varied with age and comorbidity. End-stage renal disease rates were low for all strategies (0.4% to 2.8%). Radical nephrectomy was associated with the largest decrease in estimated glomerular filtration rate and highest incidence of chronic kidney disease. Thermal ablation offered the most favorable perioperative outcomes. Partial nephrectomy showed the highest rates of urological complications but overall rates of minor/major complications were similar among interventions. Strength of evidence was moderate, low and insufficient for 11, 22 and 30 domains, respectively. Comparative studies demonstrated similar cancer specific survival across management strategies, with some differences in renal functional outcomes, perioperative outcomes and postoperative harms that should be considered when choosing a management strategy.


Early age at menarche, lung function, and adult asthma.
hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer. this study investigates whether age at menarche is related to adult lung function and asthma. among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning women's health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center. FEV(1) and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV(1) (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV(1) expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21). women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in women's respiratory health.