Knowledge and attitude of key community members towards tuberculosis: mixed method study from BRAC TB control areas in Bangladesh.
Bangladesh National Tuberculosis (TB) Control Programme adopted a number of strategies to facilitate TB diagnosis and treatment. 'Advocacy, Communication and Social Mobilization' (ACSM) was one of the key strategies implemented by BRAC (Bangladesh Rural Advancement Committee, a non-governmental development organization) TB control program. The purpose of this study is to assess the knowledge and attitudes of the key community members (KCMs) participated in ACSM in BRAC TB control areas. This study combined quantitative and qualitative methods using a mixed method approach. KCMs in three districts with low TB case detection rates were targeted to assess the ACSM program. The quantitative survey using a multi-stage random-sampling strategy was conducted among 432 participants. The qualitative study included in-depth interviews (IDIs) of a sub sample of 48 respondents. For quantitative analysis, descriptive statistics were reported using frequencies, percentages, and Chi square tests, while thematic analysis was used for qualitative part. Most (99%) of the participants had heard about TB, and almost all knew that TB is a contagious yet curable disease. More than half (53%) of the KCMs had good knowledge regarding TB, but BRAC workers were found to be more knowledgeable compared to other KCMs. However, considerable knowledge gaps were observed among BRAC community health workers. Qualitative results revealed that the majority of the KCMs were aware about the signs, symptoms and transmission pathways of TB and believed that smoking and addiction were the prime causes of transmission of TB. The knowledge about child TB was poor even among BRAC health workers. Stigma associated with TB was not uncommon. Almost all respondents expressed that young girls diagnosed with TB. This study finding has revealed varying levels of knowledge and mixed attitudes about TB among the KCMs. It also provides insight on the poor knowledge regarding child TB and indicate that despite the significant success of the TB program stigma is yet prevalent in the community. Future ACSM activities should engage community members against stigma and promote child TB related information for further improvement of BRAC TB Control Programme.


Using spaced retrieval and Montessori-based activities in improving eating ability for residents with dementia.
To construct a training protocol for spaced retrieval (SR) and to investigate the effectiveness of SR and Montessori-based activities in decreasing eating difficulty in older residents with dementia. A single evaluator, blind, and randomized control trial was used. Eighty-five residents with dementia were chosen from three special care units for residents with dementia in long-term care facilities in Taiwan. To avoid any confounding of subjects, the three institutions were randomized into three groups: spaced retrieval, Montessori-based activities, and a control group. The invention consisted of three 30-40 min sessions per week, for 8 weeks. After receiving the intervention, the Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding scores for the SR and Montessori-based activity groups were significantly lower than that of the control group. However, the frequencies of physical assistance and verbal assistance for the Montessori-based activity group after intervention were significantly higher than that of the control group, which suggests that residents who received Montessori-based activity need more physical and verbal assistance during mealtimes. In terms of the effects of nutritional status after intervention, Mini-Nutritional Assessment (MNA) in the SR group was significantly higher than that of the control group. This study confirms the efficacy of SR and Montessori-based activities for eating difficulty and eating ability. A longitudinal study to follow the long-term effects of SR and Montessori-based activities on eating ability and nutritional status is recommended.


The biology of IL-23 and IL-17 and their therapeutic targeting in rheumatic diseases.
Interleukin (IL)-23 and the related cytokine IL-17 play vital roles in immune-mediated inflammatory pathology. In the years since its discovery, IL-23 has been implicated as a central pathogenic factor in multiple rheumatic conditions and has been shown to act via a wide range of immune cells including type 17 T-helper (Th17) cells and innate-like immune cells. We review here the pivotal role of these cytokines and IL-23-responsive cells in both the bona fide autoimmune rheumatic diseases rheumatoid arthritis and systemic lupus erythematosus, as well as the spondyloarthropathies which more closely resemble the auto-inflammatory conditions. IL-23 and related cytokines have been found to be up-regulated in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy, and preclinical models suggest that they play important pathological roles in these conditions. It is anticipated that agents which target the IL-23 pathway will have profound roles in modifying the natural history of these diseases and in preventing the structural damage which occurs secondary to such chronic inflammation. This is especially relevant in the case of spondyloarthropathy in which case prevention of the novel bone formation is a particular challenge. It is also potentially pertinent for patients with rheumatoid arthritis, particularly those who do not respond to other biological therapies.


Does the inherence heuristic take us to psychological essentialism?
We argue that the claim that essence-based causal explanations emerge, hydra-like, from an inherence heuristic is incomplete. No plausible mechanism for the transition from concrete properties, or cues, to essences is provided. Moreover, the fundamental shotgun and storytelling mechanisms of the inherence heuristic are not clearly enough specified to distinguish them, developmentally, from associative or causal networks.


Hospital and outpatient health services utilization among HIV-infected patients in care in 1999.
The evolving epidemiology and therapeutic management of HIV disease has important implications for health care resource utilization in HIV-infected patients, and health care resource use data are also needed to support policy and financial decision making. Demographic, clinical, and resource utilization data were collected from 9 U.S. HIV primary and specialty care sites in calendar year 1999. Rates of resource use were calculated for hospital admission, length of hospital stay, and outpatient clinic/office visits. The sample included 5255 patients from HIV primary care sites in 3 eastern, 3 midwestern, and 3 western areas of the United States. Hospital admissions accounted for an annual mean of 297 days per 100 persons/y in 1999. Hospital days ranged from a low of 165 per 100 persons/mo for a CD4 > 500 cells/mm(3) to 840 per 100 persons/mo for a CD4 < 50 cells/mm(3) (p <.01). Mean annual outpatient clinic/office visits were 10.7 per person in 1999. A declining CD4 level and an increasing HIV-1 RNA level were both associated with higher hospital and outpatient utilization. HAART use was associated with fewer hospital days, and a higher outpatient visit rate. Injecting drug use risk was associated with an increase in hospital days. African American race was associated with a higher number of hospital days, but a lower outpatient visit rate. Female gender was associated with higher outpatient utilization. Mean monthly inpatient and outpatient expenditures in 1999 were $423 and $168, respectively. As HIV care continues to evolve, data from our network of HIV providers will be useful in quantifying changes in HIV health services utilization to guide policy makers, as well as HIV care payers and providers.


Highly focused high-frequency travelling surface acoustic waves (SAW) for rapid single-particle sorting.
High-speed sorting is an essential process in a number of clinical and research applications, where single cells, droplets and particles are segregated based on their properties in a continuous flow. With recent developments in the field of microscale actuation, there is increasing interest in replicating the functions available to conventional fluorescence activated cell sorting (FACS) flow cytometry in integrated on-chip systems, which have substantial advantages in cost and portability. Surface acoustic wave (SAW) devices are ideal for many acoustofluidic applications, and have been used to perform such sorting at rates on the order of kHz. Essential to the accuracy of this sorting, however, is the dimensions of the region over which sorting occurs, where a smaller sorting region can largely avoid inaccurate sorting across a range of sample concentrations. Here we demonstrate the use of flow focusing and a highly focused SAW generated by a high-frequency (386 MHz), 10 μm wavelength set of focused interdigital transducers (FIDTs) on a piezoelectric lithium niobate substrate, yielding an effective sorting region only ~25 μm wide, with sub-millisecond pulses generated at up to kHz rates. Furthermore, because of the use of high frequencies, actuation of particles as small as 2 μm can be realized. Such devices represent a substantial step forward in the evolution of highly localized forces for lab-on-a-chip microfluidic applications.


Gonadal mesoderm and fat body initially follow a common developmental path in Drosophila.
During gastrulation, the Drosophila mesoderm invaginates and forms a single cell layer in close juxtaposition to the overlying ectoderm. Subsequently, particular cell types within the mesoderm are specified along the anteroposterior and dorsoventral axes. The exact developmental pathways that guide the specification of different cell types within the mesoderm are not well understood. We have analyzed the developmental relationship between two mesodermal tissues in the Drosophila embryo, the gonadal mesoderm and the fat body. Both tissues arise from lateral mesoderm within the eve domain. Whereas in the eve domain of parasegments 10-12 gonadal mesoderm develops from dorsolateral mesoderm and fat body from ventrolateral mesoderm, in parasegments 4-9 only fat body is specified. Our results demonstrate that the cell fate decision between gonadal mesoderm and fat body identity within dorsolateral mesoderm along the anteroposterior axis is determined by the combined actions of genes including abdA, AbdB and srp; while srp promotes fat body development, abdA allows gonadal mesoderm to develop by repressing srp function. Furthermore, we present evidence from genetic analysis suggesting that, before stage 10 of embryogenesis, gonadal mesoderm and the fat body have not yet been specified as different cell types, but exist as a common pool of precursor cells requiring the functions of the tin, zfh-1 and cli genes for their development.


Risk assessment of white willow (Salix alba) in food.
This Technical Report contains a description of the activities within the work programme of the EU-FORA Fellowship on the risk assessment of white willow in food. The bark of different varieties of willow has had a long history of medical use as a means to reduce fever and as a painkiller. Willow bark is also used in weight loss and sports performance food supplements. The labelling of these products usually does not mention any restrictions to the length of use. The recommended doses for foods differ, sometimes exceeding doses recommended for pharmaceuticals. A systematic literature review on adverse effects potentially resulting from oral exposure to white willow (Salix alba) was performed. The aim of the study was to assess the risk for humans when consuming white willow bark in food. The preliminary results show that despite the long history of use only very limited data on toxicity of white willow bark are available. However, anaphylactic reactions in people with a history of allergy to salicylates may occur. Some other adverse effects of salicylates are considered to be of low relevance for the long-time consumption of white willow bark, mainly due to relatively low concentrations of salicin and the presence of compounds with gastroprotective action. However, it seems that the content of heavy metals, mainly cadmium, should be further addressed in risk assessment of white willow bark in food.


Do Patients Respond to Posted Emergency Department Wait Times: Time-Series Evidence From the Implementation of a Wait Time Publication System in Hamilton, Canada.
One proposed solution to prolonged emergency department (ED) wait times is a publicly available website that displays estimated ED wait times. This could provide information to patients so that they may choose sites with low wait times, which has the potential to smooth the overall wait times in EDs across a health system. We describe the effect of a novel city-wide ED wait time website on patient volume distributions throughout the city of Hamilton, Ontario, Canada. We compared the number of new patients arriving every 15 minutes during 2 separate time periods-before and after a publicly viewable wait time website was made available. For each ED site, the effect of the posted wait time was measured by assessing its association with the total number of patient arrivals in the subsequent hour at the same site and at all other sites in Hamilton. Linear models showed clinically modest changes in patient volumes when wait times changed. However, nonlinear models showed that a 60-minute increase in wait time at a site was associated with 10% fewer patients presenting over the next hour. Larger negative associations were observed at community hospitals and urgent care centers. Increases in wait times at a given site were also associated with increased patient volumes at other sites in the system. After the implementation of a public wait time website, elevated wait times led to fewer patients at the same site but more patient visits at other sites. This may be consistent with the wait time tracker inducing patients to avoid sites with high wait times and instead visit alternate sites in Hamilton, but only when wait times were very high.


Population Dynamics of Early Human Migration in Britain.
Early human migration is largely determined by geography and human needs. These are both deterministic parameters when small populations move into unoccupied areas where conflicts and large group dynamics are not important. The early period of human migration into the British Isles provides such a laboratory which, because of its relative geographical isolation, may allow some insights into the complex dynamics of early human migration and interaction. We developed a simulation code based on human affinity to habitable land, as defined by availability of water sources, altitude, and flatness of land, in choosing the path of migration. Movement of people on the British island over the prehistoric period from their initial entry points was simulated on the basis of data from the megalithic period. Topographical and hydro-shed data from satellite databases was used to define habitability, based on distance from water bodies, flatness of the terrain, and altitude above sea level. We simulated population movement based on assumptions of affinity for more habitable places, with the rate of movement tempered by existing populations. We compared results of our computer simulations with genetic data and show that our simulation can predict fairly accurately the points of contacts between different migratory paths. Such comparison also provides more detailed information about the path of peoples' movement over ~2000 years before the present era. We demonstrate an accurate method to simulate prehistoric movements of people based upon current topographical satellite data. Our findings are validated by recently-available genetic data. Our method may prove useful in determining early human population dynamics even when no genetic information is available.


Relationship of Serum Progesterone and Progesterone Metabolites with Mammographic Breast Density and Terminal Ductal Lobular Unit Involution among Women Undergoing Diagnostic Breast Biopsy.
The association of progesterone/progesterone metabolites with elevated mammographic breast density (MBD) and delayed age-related terminal duct lobular unit (TDLU) involution, strong breast cancer risk factors, has received limited attention. Using a reliable liquid chromatography-tandem mass-spectrometry assay, we quantified serum progesterone/progesterone metabolites and explored cross-sectional relationships with MBD and TDLU involution among women, ages 40-65, undergoing diagnostic breast biopsy. Quantitative MBD measures were estimated in pre-biopsy digital mammograms. TDLU involution was quantified in diagnostic biopsies. Adjusted partial correlations and trends across MBD/TDLU categories were calculated. Pregnenolone was positively associated with percent MBD-area (MBD-A, rho: 0.30; p-trend = 0.01) among premenopausal luteal phase women. Progesterone tended to be positively associated with percent MBD-A among luteal phase (rho: 0.26; p-trend = 0.07) and postmenopausal (rho: 0.17; p-trend = 0.04) women. Consistent with experimental data, implicating an elevated 5α-pregnanes/3α-dihydroprogesterone (5αP/3αHP) metabolite ratio in breast cancer, higher 5αP/3αHP was associated with elevated percent MBD-A among luteal phase (rho: 0.29; p-trend = 0.08), but not postmenopausal women. This exploratory analysis provided some evidence that endogenous progesterone and progesterone metabolites might be correlated with MBD, a strong breast cancer risk factor, in both pre- and postmenopausal women undergoing breast biopsy. Additional studies are needed to understand the role of progesterone/progesterone metabolites in breast tissue composition and breast cancer risk.


The impact of scaffolding and overhearing on young children's use of the spatial terms between and middle.
The primary goal was to specify the impact of scaffolding and overhearing on young children's use of the spatial terms between and middle. Four- and five-year-old children described the location of a mouse hidden between two furniture items in a dollhouse with assistance from a parent. Children's use of between and middle increased significantly across trials, and in concert, parents' directive scaffolding involving middle decreased across trials. In the second study, three common scaffolding types (Between Directive, Middle Directive, non-directive) were compared with a no prompt condition by having children receive prompts from a doll and with overhearing conditions in which children overheard conversations between two adult experimenters containing between or middle. Children's use of between and middle was much more frequent following directive prompting than following non-directive prompting, no prompting, or overhearing. Moreover, children showed some evidence of using between and middle in response to non-directive prompting and overhearing.


Identification, cloning, and characterization of PWL2, a gene for host species specificity in the rice blast fungus.
Genetic analysis of host specificity in the rice blast fungus (Magnaporthe grisea) identified a single gene, PWL2 (for Pathogenicity toward Weeping Lovegrass), that exerts a major effect on the ability of this fungus to infect weeping lovegrass (Eragrostis curvula). The allele of the PWL2 gene conferring nonpathogenicity was genetically unstable, with the frequent appearance of spontaneous pathogenic mutants. PWL2 was cloned based on its map position. Large deletions detected in pathogenic mutants guided the gene cloning efforts. Transformants harboring the cloned PWL2 gene lost pathogenicity toward weeping lovegrass but remained fully pathogenic toward other host plants. Thus, the PWL2 host species specificity gene has properties analogous to classical avirulence genes, which function to prevent infection of certain cultivars of a particular host species. The PWL2 gene encodes a glycine-rich, hydrophilic protein (16 kD) with a putative secretion signal sequence. The pathogenic allele segregating in the mapping population, pwl2-2, differed from PWL2 by a single base pair substitution that resulted in a loss of function. The PWL2 locus is highly polymorphic among rice pathogens from diverse geographic locations.


Use of a portable real-time reverse transcriptase-polymerase chain reaction assay for rapid detection of foot-and-mouth disease virus.
To evaluate a portable real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay designed to detect all 7 viral serotypes of foot-and-mouth disease virus (FMDV). Laboratory and animal studies. Viruses grown in tissue culture and animals experimentally infected with FMDV. 1 steer, pig, and sheep were infected with serotype O FMDV. Twenty-four hours later, animals were placed in separate rooms that contained 4 FMDV-free, healthy animals of the same species. Oral and nasal swab specimens, oropharyngeal specimens obtained with a probang, and blood samples were obtained at frequent intervals, and animals were observed for fever and clinical signs of foot-and-mouth disease (FMD). Samples from animals and tissue cultures were assayed for infectious virus and viral RNA. The assay detected viral RNA representing all 7 FMDV serotypes grown in tissue culture but did not amplify a panel of selected viruses that included those that cause vesicular diseases similar to FMD; thus, the assay had a specificity of 100%, depending on the panel selected. The assay also met or exceeded sensitivity of viral culture on samples from experimentally infected animals. In many instances, the assay detected viral RNA in the mouth and nose 24 to 96 hours before the onset of clinical disease. The assay reagents are produced in a vitrified form, which permits storage and transportation at ambient temperatures. The test can be performed in 2 hours or less on a portable instrument, thus providing a rapid, portable, sensitive, and specific method for detection of FMDV.


D2-40: a reliable marker in the diagnosis of pleural mesothelioma.
Malignant mesotheliomas of the pleura, peritoneum and pericardium can easily be confused with either metastatic adenocarcinomas or reactive pleural lesions. D2-40, a monoclonal antibody used as a marker for seminomatous germ cell tumours and lymphatic endothelial cells, was recently described in mesothelial cells and type I but not type II pneumocytes. The immunoreactivities of D2-40 in 76 lung carcinomas of different histological types (adenocarcinomas, squamous cell, small cell, and bronchioloalveolar carcinomas) were compared with those of 36 pleural epithelioid and sarcomatoid mesotheliomas and 5 specimens of chronic pleuritis. While all 18 analysed epithelioid mesotheliomas displayed a strong membranous immunostaining, 18 sarcomatoid mesotheliomas showed no, or a merely faint, cytoplasmic signal, comparable with fibroblasts in chronic pleuritis. Out of all analysed lung carcinomas, 49 showed no immunoreactivity for D2-40 (64%), while the other 27 (36%) showed a focal weak to moderate and only cytoplasmic signal. We regard D2-40 as a valid marker in the differential diagnosis of epithelioid mesotheliomas versus pulmonary adenocarcinomas. However, this marker may not properly label sarcomatoid mesotheliomas or distinguish them from reactive pleural lesions.


Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis.
The COVID-19 pandemic represents one of the world's most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. We identified 78 bibliographic citations. After the reviewers' screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34-0.72) and 0.28 (0.20-0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.


Estimating the effect of a potential policy to restrict tobacco retail availability in New Zealand.
Reducing tobacco retailer density is suggested to be a key component of tobacco endgames. Where tobacco retail reduction policies exist, 'grandfathering' is typically used, where existing retailers are exempt from restrictions aimed at reducing outlet density. We examined the possible impact on tobacco outlet density in New Zealand of a policy preventing new retail outlets from selling tobacco, but allowing existing retail outlets to continue selling tobacco until they ceased trading or relocated. We obtained data on numbers of tobacco outlets and the number of outlet closures recorded annually from 2006 to 2016. We calculated the mean and the lowest and highest 3-year rolling average closure rates for each type of tobacco outlet. We projected decreases in the number of tobacco outlets that would hypothetically be permitted to sell tobacco from 2020 onwards and estimated when the combined number of tobacco outlets would decline by 50% and 95%. Based on mean annual closure rates, the total number of tobacco outlets would decrease by 50% by 2032 and a 95% reduction could be achieved by 2072. By 2025, the number of tobacco outlets would decrease by 27%; by 2050, this reduction would reach 84%. A tobacco retail reduction policy that prevented new retail outlets from selling tobacco and grandfathered existing retailers would be unlikely to achieve New Zealand's target of a 95% reduction in tobacco outlet density within several decades of being enacted. Nonetheless, this policy could achieve a 50% reduction in tobacco retail availability in the first decade of implementation.


Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke.
White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis. We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging-confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups. The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI]]=1.14 [1.06-1.22]; P=0.0003), in patients both with and without WMH (WMH: OR [95% CI]=1.15 [1.05-1.26]; P=0.003 and no WMH: OR [95% CI]=1.11 [1.02-1.21]; P=0.019). Conversely, the risk score was not associated with cardioembolic stroke (OR [95% CI]=1.03 [0.97-1.09]; P=0.63) or large vessel stroke (OR [95% CI]=0.99 [0.93,1.04]; P=0.39). However, none of the WMH-associated single nucleotide polymorphisms passed Bonferroni-corrected significance for association with lacunar stroke. Genetic variants that influence WMH are associated with an increased risk of lacunar stroke but not cardioembolic or large vessel stroke. Some genetic susceptibility factors seem to be shared across different radiological manifestations of small vessel disease.


Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation.
Although ciliary neurotrophic factor (CNTF) is a potent survival factor for many types of neurons and glial cells in vitro, there is currently no evidence that it participates in normal development. Here we show that CNTF greatly enhances the rate of oligodendrocyte generation. Proliferation of oligodendrocyte precursor cells purified from rodent optic nerves and cultured in platelet-derived growth factor-containing medium is significantly increased by CNTF. Similarly, the number of proliferating oligodendrocyte precursor cells in developing optic nerves of transgenic mice lacking CNTF is decreased by up to threefold and the number of oligodendrocytes is transiently decreased; proliferation is restored to normal by the delivery of exogenous CNTF into the developing optic nerve. Both oligodendrocyte number and myelination ultimately attain wild-type values in CNTF-deficient adult mice, indicating that CNTF is not necessary for either oligodendrocyte differentiation or myelination, although it normally accelerates oligodendrocyte development by enhancing the proliferation of oligodendrocyte precursor cells.


Clinical characteristics and outcomes of patients with acute coronary syndrome and prior coronary artery bypass grafting in a large middle eastern cohort.
Acute Coronary Syndrome (ACS) can occur in patients with prior coronary artery bypass grafting (CABG). In the Gulf Registry of acute coronary events (Gulf RACE), we identified the clinical characteristics and in-hospital outcomes of these patients. Clinical characteristics and in-hospital outcomes for 461 ACS patients with prior CABG are compared to 7715 ACS patients without prior CABG enrolled from 64 hospitals in 6 Gulf countries over a 6-month period. The overall incidence of ACS with prior CABG was 5.6% out of 8176 patients. The ACS with prior CABG were older (63 vs 55 years, P<0.0001), had more history of diabetes (62.3 vs 37.6%, P <0.0001), dyslipidemia (70.3 vs 29.5%, P<0.0001), and hypertension (75.7 vs 47.8%, P<0.0001) compared with the non-CABG group. They presented more frequently with dyspnea (14.8 vs 9.5%, P<0.0005), non-ST segment elevation myocardial infarction (41.4 vs 31.6%, P<0.0001) and echocardiographic evidence of left ventricular dysfunction (49.4 vs 29.8%, P<0.0001) than ACS without prior CABG. They had a complicated in-hospital course with more recurrent ischemia (13.9 vs 9.3%, P=0.0011), heart failure (24.1 vs 15.7%), and stroke (2.2 vs 0.6%) compared with those without CABG. The in-hospital mortality rate was 5.6% in the CABG group compared with 3.5% in the ACS without prior CABG group. After adjusting for confounders, prior CABG was independently associated with recurrent ischemia and shock, more in patients presenting with ST elevation than non-ST elevation ACS. Patients with ACS and prior CABG are a high-risk group with poor outcomes irrespective of their older age and comorbidities. They should be identified and treated differently to improve their outcomes.


The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD.
One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. UKCRN ID 14214.


Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: potential for new biomarkers to aid in the diagnosis of breast cancer.
Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.


Long-Term Outcomes in Patients With BRAF V600-Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib.
Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.


Vertical transmission of highly similar bla CTX-M-1-harboring IncI1 plasmids in Escherichia coli with different MLST types in the poultry production pyramid.
The purpose of this study was to characterize sets of extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae collected longitudinally from different flocks of broiler breeders, meconium of 1-day-old broilers from theses breeder flocks, as well as from these broiler flocks before slaughter. Five sets of ESBL-producing Escherichia coli were studied by multi-locus sequence typing (MLST), phylogenetic grouping, PCR-based replicon typing and resistance profiling. The bla CTX-M-1-harboring plasmids of one set (pHV295.1, pHV114.1, and pHV292.1) were fully sequenced and subjected to comparative analysis. Eleven different MLST sequence types (ST) were identified with ST1056 the predominant one, isolated in all five sets either on the broiler breeder or meconium level. Plasmid sequencing revealed that bla CTX-M-1 was carried by highly similar IncI1/ST3 plasmids that were 105 076 bp, 110 997 bp, and 117 269 bp in size, respectively. The fact that genetically similar IncI1/ST3 plasmids were found in ESBL-producing E. coli of different MLST types isolated at the different levels in the broiler production pyramid provides strong evidence for a vertical transmission of these plasmids from a common source (nucleus poultry flocks).


[A case of neurofibromatosis-1 in which severe bleeding was observed from a neurofibroma under the scalp].
Neurofibroma is a representative external abnormality observed along with café-au-lait spots in association with neurofibromatosis type 1 (NF-1). We encountered a case of NF-1 in which severe bleeding was observed from a neurofibroma under the scalp due to minor trauma. Only four similar cases have been reported in the past literature and we believed that it was a significantly rare case, and we herein report the case with bibliographical considerations. The subject was a 23-year-old male. He was gently hit on the right side of the head during work and the bruised site gradually became bloated. Even on the following day, the bloating continued and he also started feeling severe pain, and as a result, he visited our emergency department. A head CT scan revealed a subcutaneous high-density area from the right-frontal area of the head to the side of the head that appeared to be a hematoma. The pain was severe and we therefore performed emergency surgery to remove the subcutaneous hematoma, but due to severe bleeding during the operation, we ultimately removed only part of the hematoma. However, because the pain was relieved, he was discharged from the hospital and he subsequently stopped visiting the hospital regularly. Three years later, he visited our department again with similar head bloating due to a mild head bruise. When surgery was performed again, an obvious neoplastic lesion was observed along with the subcutaneous hematoma. The pathological findings suggested it was a neurofibroma but no malignant findings were observed.


WristPrint: Characterizing User Re-identification Risks from Wrist-worn Accelerometry Data.
Public release of wrist-worn motion sensor data is growing. They enable and accelerate research in developing new algorithms to passively track daily activities, resulting in improved health and wellness utilities of smartwatches and activity trackers. But, when combined with sensitive attribute inference attack and linkage attack via re-identification of the same user in multiple datasets, undisclosed sensitive attributes can be revealed to unintended organizations with potentially adverse consequences for unsuspecting data contributing users. To guide both users and data collecting researchers, we characterize the re-identification risks inherent in motion sensor data collected from wrist-worn devices in users' natural environment. For this purpose, we use an open-set formulation, train a deep learning architecture with a new loss function, and apply our model to a new data set consisting of 10 weeks of daily sensor wearing by 353 users. We find that re-identification risk increases with an increase in the activity intensity. On average, such risk is 96% for a user when sharing a full day of sensor data.


Physical activity and the risk of colorectal cancer in Lynch syndrome.
Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk in people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n = 807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49 and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-hr/week) during the age-period of cancer diagnosis or censoring (near-term exposure) and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. <3.5 MET-hr/week, 0.71; 95% CI, 0.53-0.96). The strength and direction of associations were similar for long-term physical activity, although the associations were not nominally significant. Our results suggest that physical activity is inversely associated with the risk of colorectal cancer for people with Lynch syndrome; however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk in people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk.


No Benefit After THA Performed With Computer-assisted Cup Placement: 10-year Results of a Randomized Controlled Study.
Computer-assisted surgery (CAS) for cup placement has been developed to improve the functional results and to reduce the dislocation rate and wear after total hip arthroplasty (THA). Previously published studies demonstrated radiographic benefits of CAS in terms of implant position, but whether these improvements result in clinically important differences that patients might perceive remains largely unknown. We hypothesized that THA performed with CAS would improve 10-year patient-reported outcomes measured by validated scoring tools, reduce acetabular polyethylene wear as measured using a validated radiological method, and increase survivorship. Sixty patients operated on for a THA between April 2004 and April 2005 were randomized into two groups using either the CAS technique or a conventional technique for cup placement. All patient candidates for a THA with the diagnosis of primary arthritis or avascular necrosis were eligible for the CAS procedure and randomly assigned to the CAS group by the Hospital Informatics Department with use of a systematic sampling method. The patients assigned to the freehand cup placement group were matched for sex, age within 5 years, pathological condition, operatively treated side, and body mass index within 3 points. All patients were operated on through an anterolateral approach (patient in the supine position) using cementless implants. In the CAS group, a specific surgical procedure using an imageless cup positioning computer-based navigation system was performed. There were 16 men and 14 women in each group; mean age was 62 years (range, 24-80 years), and mean body mass index was 25 ± 3 kg/m(2). No patient was lost to followup at 10 years, but five patients have died (two in the CAS group and three in the control group). At the 10-year followup, an independent observer blinded to the type of technique performed patients' evaluation. Cup positioning was evaluated postoperatively using a CT scan in the two groups with results previously published. At 10 years, we assessed subjective functional outcome and quality of life using validated questionnaires (SF-12, Harris hip score [HHS], Hip injury and Osteoarthritis Outcome Score). Wear rate was then evaluated on standardized radiographs using a previously validated semiautomated computer analogic measurement method (dual circle method). Complications and survivorship were compared between groups. With our available sample size, this study had 80% power to detect a difference of 4 points out of 100 on the HHS at the p < 0.05 level. With the numbers available, we found we found no differences between groups regarding HSS at last followup 95.3 ± 5.9 points (CAS group) versus 96.2 ± 4.5 points, a mean difference of 0.9 points (95% confidence interval [CI], -4.3 to 4.6; p = 0.6). There was no difference between the groups in terms of the mean (± SD) acetabular linear wear at 10 years. The mean wear was 0.71 ± 0.6 mm in the CAS group versus 0.77 ± 0.52 mm in the control group, a mean difference of 0.06 mm (95% CI, -0.1 to 0.2; p = 0.54). With the numbers available, there was no difference between the CAS group and the conventional THA groups in terms of survivorship free from aseptic loosening (100%; 95% CI, 100%-95%, versus 100%; 95% CI, 100%-94%; p = 0.3). Our observations suggest that CAS used for cup placement does not confer any substantial advantage in function, wear rate, or survivorship at 10 years after THA. Because CAS is associated with added costs and surgical time, future studies need to identify what clinically relevant advantages it offers, if any, to justify its continued use in THA. Level II, therapeutic study.


Diabetes Training for Community Health Workers.
A 2.5-month diabetes education training for community health workers (CHWs) was developed, implemented, and evaluated. Training methods used included case studies, role-playing, and lectures. Exams were used throughout the training for its evaluation. Teaching was delivered by different ways: a one day American Diabetes Association (ADA) course; a five day Diabetes Self-Management Program (DSMP); Conversation Maps; and a series of seven National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) diabetes education booklets. Qualitative and quantitative evaluative methods were used during and after the training. The CHWs' diabetes knowledge was evaluated by a pre- and post-test Diabetes Knowledge Questionnaire (DKQ). The post-test was conducted one week after completing the training. The findings showed that the diabetes knowledge of the CHWs increased. Diabetes competencies and evaluative tools need to be developed specific for CHWs as a way to standardize all CHW diabetes trainings.


A longitudinal study to assess the persistence of vancomycin-resistant Enterococcus faecium (VREF) on an intensive broiler farm in the United Kingdom.
Seven years after the ban of avoparcin, VREF could still be isolated within sectors of the UK broiler industry. The aim of this study was to assess whether there is a carryover of VREF between consecutive flocks of birds, to conduct a preliminary investigation of possible routes of entry of VREF into broiler houses and to follow the dynamics of VREF shed by growing birds. A series of nine visits were made to two of six houses on a conventional broiler farm. A total of 343 vanA VREF were recovered from environmental (95/843) and faecal (248/416) samples. Significant differences were observed in the carryover of VREF between pre- and postcohort postcleaning and disinfection visits (RR 0.57, P=0.006). Ninety-nine percent of the VREF isolates were resistant to more than five antimicrobials, with 42 isolates (n=49) positive for erm(B) and 32 (n=40) for vat(E). Pulsed field gel electrophoresis (PFGE) typing identified 50 PFGE types within 15 different PFGE clusters of 90% similarity, demonstrating a high level of genetic diversity within VREF populations from epidemiologically related broiler flocks and broiler houses. Further characterization of Tn1546 from different clones showed a low diversity of Tn-types, suggesting horizontal transfer of resistance determinants between different genetic clones. Thus, this study does not only show the persistence of VREF but also of multi-drug resistant lineages of VREF.


Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes.
The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.


Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1.
As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.


Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature.
Small vascular units consisting of an arteriole, its capillaries, and the emerging venule (ACV units) were identified in the rat omentum and mesentery. They were fixed in situ and processed for electron microscopy either as whole units or as dissected segments. Systematic examination of the latter (in thin sections, as well as in freeze-cleaved preparations) showed that the intercellular junctions of the vascular endothelium vary characteristically from one segment to another in the microvasculature. In arterioles, the endothelium has continuous and elaborate tight junctions with interpolated large gap junctions. The capillary endothelium is provided with tight junctions formed by either branching or staggered strands; gap junctions are absent at this level. The pericytic venules exhibit loosely organized endothelial junctions with discontinuous low-profile ridges and grooves, usually devoid of particles. No gap junctions were found in these vessels. The endothelium of muscular venules has the same type of junctions (discontinuous ridges and grooves of low profile); in addition, it displays isolated gap junctions of smaller size and lower frequency than in arterioles. The term communicating junction (macula communicans) is proposed as a substitute for gap junctions, since the latter is inappropriate, in general, and confusing in the special case of the vascular endothelium.


Identification of immunoreactive proteins of Mycobacterium avium subsp. paratuberculosis.
Mycobacterium avium subsp. paratuberculosis (MAP) is the cause of a chronic enteritis of ruminants (bovine paratuberculosis (PTB)--Johne's disease) that is associated with enormous worldwide economic losses for the animal production. Diagnosis is based on observation of clinical signs, the detection of antibodies in milk or serum, or evaluation of bacterial culture from feces. The limit of these methods is that they are not able to detect the disease in the subclinical stage and are applicable only when the disease is already advanced. For this reason, the main purpose of this study is to use the MAP proteome to detect novel immunoreactive proteins that may be helpful for PTB diagnoses. 2DE and 2D immunoblotting of MAP proteins were performed using sera of control cattle and PTB-infected cattle in order to highlight the specific immunoreactive proteins. Among the assigned identifiers to immunoreactive spots it was found that most of them correspond to surface-located proteins while three of them have never been described before as antigens. The identification of these proteins improves scientific knowledge that could be useful for PTB diagnoses. The sequence of the identified protein can be used for the synthesis of immunoreactive peptides that could be screened for their immunoreaction against bovine sera infected with MAP. All MS data have been deposited in the ProteomeXchange consortium with identifier PXD001159 and DOI 10.6019/PXD001159.


A selected ribozyme catalyzing diverse dipeptide synthesis.
The sequence of events by which protein, RNA, and DNA emerged during early biological evolution is one of the most profound questions regarding the origin of life. The contemporary role of aminoacyl-adenylates as intermediates in both ribosomal and nonribosomal peptide synthesis suggests that they may have served as substrates for uncoded peptide synthesis during early evolution. We report a highly active peptidyl transferase ribozyme family, isolated by in vitro selection, that efficiently catalyzes dipeptide synthesis by using an aminoacyl-adenylate substrate. It was characterized by sequence and structural analysis and kinetic studies. Remarkably, the ribozyme catalyzed the formation of 30 different dipeptides, the majority of rates being within 5-fold that of the Met-Phe dipeptide required by the selection. The isolation of this synthetic ribozyme fosters speculation that ribozyme-mediated uncoded peptide synthesis may have preceded coded peptide synthesis.


Perceptions of community trust and safety - consequences for children's well-being in rural and urban contexts.
To explore the associations between subjective well-being and perceptions of community trust and safety amongst children in rural and urban areas. The study used self-reported data from the 2001/2002 Swedish cross-national WHO study Health Behaviour in School-aged Children. The sample consisted of 3852 children aged 11-15 years, living in different residential areas. Bivariate analyses and multivariate logistic regression were performed. The results indicated that a greater proportion of children in urban areas perceived low community trust and safety, compared with children in rural areas. Further, the multivariate analysis revealed that perceived community trust and safety significantly impacts upon children's subjective well-being in both rural and urban contexts. Children's perceptions of trust and safety have different magnitudes in urban and rural areas. The associations of perceptions of community trust and safety for children's subjective well-being are relevant in both urban and rural areas. As perceptions of low trust and safety in the community seem to be related to low subjective well-being, efforts to encourage community trust and safety should be included amongst the key priorities in community health promotion.


Different Aspects of Psychological Ill Health in a National Sample of Swedish Parents after Successful Paediatric Stem Cell Transplantation.
Paediatric hematopoietic stem cell transplantation (HSCT) may have great psychological impact on parents during the intense treatment period as well as many years after a successful transplantation. Since different psychological disorders require different interventions, a differentiation of general distress into specific types of psychological ill health is essential. The aim of this descriptive study was to distinguish anxiety, depression, and burnout, and investigate occurrence and co-occurrence of these in a national Swedish sample of parents of children who had undergone HSCT and survived. Established self-report instruments (Hospital Anxiety and Depression Scale, posttraumatic stress checklist, and Shirom-Melamed Burnout Questionnaire) were used to assess parents' subjective suffering. the child had to be alive; ≤18 years of age; >6 months since HSCT. Four hundred twenty-one eligible parents (220 mothers and 201 fathers) were identified, of whom 284 choose to participate (response rate 67%). In total, 134 parents (87 mothers, 47 fathers) reported clinically relevant levels of one or more of the assessed types of psychological ill health, representing 48% of the responding participants and 32% of the entire national population of parents of children who had undergone HSCT and survived. Anxiety and/or burnout were reported most frequently. A majority reported more than one type of psychological ill health. Depression only was rare. The findings underscore the importance of recognizing-in research as well as in clinical practice-that different types of psychological ill health may affect parents after successful HSCT. When parents present with psychological suffering, a referral for qualified assessment is warranted to obtain the proper treatment.


Pulmonary arteries: imaging of pulmonary embolism and beyond.
The pulmonary arteries are not just affected by thrombus. Various acquired and congenital conditions can also affect the pulmonary arteries. In this review we discuss cross sectional imaging modalities utilized for the imaging of the pulmonary arteries. Acquired pulmonary artery entities, including pulmonary artery sarcoma (PAS), vasculitis, aneurysm, and arteriovenous malformations, and congenital anomalies in adults, including proximal interruption of the pulmonary artery, pulmonary sling, pulmonary artery stenosis, and idiopathic dilatation of the pulmonary trunk, are also discussed. An awareness of these entities and their imaging findings is important for radiologists interpreting chest imaging.


T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis.
The immunological synapse (IS) serves a dual role for sustained T cell receptor (TCR) signaling and for TCR downregulation. TC21 (Rras2) is a RRas subfamily GTPase that constitutively associates with the TCR and is implicated in tonic TCR signaling by activating phosphatidylinositol 3-kinase. In this study, we demonstrate that TC21 both cotranslocates with the TCR to the IS and is necessary for TCR internalization from the IS through a mechanism dependent on RhoG, a small GTPase previously associated with phagocytosis. Indeed, we found that the TCR triggers T cells to phagocytose 1-6 μm beads through a TC21- and RhoG-dependent pathway. We further show that TC21 and RhoG are necessary for the TCR-promoted uptake of major histocompatibility complex (MHC) from antigen-presenting cells. Therefore, TC21 and RhoG dependence underlie the existence of a common phagocytic mechanism that drives TCR internalization from the IS together with its peptide-MHC ligand.


Perinatal outcome and long-term follow-up of extremely low birth weight infants depending on the mode of delivery.
To assess the effect of the mode of delivery (vaginal or cesarean section) on survival, morbidity, and long-term psychomotor development of extremely low birth weight (ELBW) infants. A longitudinal observational study including 138 ELBW infants (73 born by c-section and 65 vaginally) was conducted. We analyzed the survival and short-term morbidity. We also studied the long-term neurocognitive and motor development using the McCarthy Scales of Children's Abilities (MSCA). Mortality was significantly higher in newborns delivered vaginally (49.3%) than those delivered by c-section (23.1%). Newborns delivered vaginally had a higher incidence of retinopathy and peri-intraventricular hemorrhage (P-IVH). Children who died had lower gestational age at birth and lower birth weight. After multivariate analysis only birth weight, gestational age at birth and P-IVH were independently associated to mortality. Regarding the long-term evaluation (MSCA), we observed that children born by c-section had lower incidence of abnormal results. The mode of delivery does not affect survival. Cesarean section provides lower morbidity and better prognosis for neurodevelopment long-term outcome in ELBW infants.


Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve.
Despite the common occurrence of aortic stenosis, the cellular causes of the disorder are unknown, in part because of the absence of experimental models. We hypothesized that atherosclerosis and early bone matrix expression in the aortic valve occurs secondary to experimental hypercholesterolemia and that treatment with atorvastatin modifies this transformation. To test this hypothesis, we developed an experimental hypercholesterolemic rabbit model. New Zealand White rabbits (n=48) were studied: group 1 (n=16), normal diet; group 2 (n=16), 1% (wt/wt) cholesterol diet; and group 3 (n=16), 1% (wt/wt) cholesterol diet plus atorvastatin (3 mg/kg per day). The aortic valves were examined with hematoxylin and eosin stain, Masson trichrome, macrophage (RAM 11), proliferation cell nuclear antigen (PCNA), and osteopontin immunostains. Cholesterol and highly sensitive C-reactive protein (hsCRP) serum levels were obtained by standard assays. Computerized morphometry and digital image analysis were performed for quantifying PCNA (% area). Electron microscopy and immunogold labeling were performed for osteopontin. Semiquantitative RT-PCR was performed for the osteoblast bone markers [alkaline phosphatase, osteopontin, and osteoblast lineage-specific transcription factor (Cbfa-1)]. There was an increase in cholesterol, hsCRP, PCNA, RAM 11, and osteopontin and osteoblast gene markers (alkaline phosphatase, osteopontin, and Cbfa-1) in the cholesterol-fed rabbits compared with control rabbits. All markers except hsCRP were reduced by atorvastatin. These findings of increased macrophages, PCNA levels, and bone matrix proteins in the aortic valve during experimental hypercholesterolemia provide evidence of a proliferative atherosclerosis-like process in the aortic valve associated with the transformation to an osteoblast-like phenotype that is inhibited by atorvastatin.


Mentally represented motor actions in normal aging. I. Age effects on the temporal features of overt and covert execution of actions.
The present study examines the temporal features of overt and covert actions as a function of normal aging. In the first experiment, we tested three motor tasks (walking, sit-stand-sit, arm pointing) that did not imply any particular spatiotemporal constraints, and we compared the duration of their overt and covert execution in three different groups of age (mean ages: 22.5, 66.2 and 73.4 years). We found that the ability of generating motor images did not differentiate elderly subjects from young subjects. Precisely, regarding overt and covert durations, subjects presented similarities for the walking and pointing tasks and dissimilarities for the stand-sit-stand task. Furthermore, the timing variability of imagined movements was always greater compared to actual movements and was of the same amount in the three groups of age. In the second experiment, we investigated the effect of age (three groups with mean ages: 22, 64.8 and 73.2 years) upon temporal characteristics of covert and overt movements involving strong spatiotemporal constraints (speed/accuracy trade-off paradigm). During overt execution young and elderly subjects respected Fitts's law despite the fact that movement speed progressively decreased with age. Thus, while execution is deteriorated, the motor preparation process is still intact in old age, and follows well-known laws of biological motions. For covert execution, movement speed progressively decreased with age but elderly subjects did not respect Fitts's law. This suggests that the generation and control of motor intentions that consciously do not come to execution, particularly those concerning complex motor actions are progressively perturbed in the aging brain.


The effect of host resistance to tick infestation on the transmission of Thogoto virus by ticks.
Tick-borne virus transmission was examined using guinea-pigs and hamsters previously infested with ticks. Guinea-pigs developed immunity to Rhipicephalus appendiculatus after a single exposure to the ticks. Nymphal and adult stages that fed on resistant guinea-pigs had increased mortality during feeding, and reduced engorged weights. Egg production from female ticks fed on resistant hosts fell by at least 50%. Guinea-pigs maintained high levels of immunity to tick infestation for at least 210 days after the initial exposure. In contrast, hamsters did not develop resistance to ticks even after three or four infestations. R. appendiculatus adults infected with Thogoto (THO) virus (donors) were allowed to co-feed with uninfected nymphs (recipients) on either resistant or naive guinea-pigs. The number of recipient ticks that acquired virus was significantly reduced on resistant guinea-pigs. In contrast, feeding on pre-infested hamsters did not affect tick-borne transmission of THO virus. Host resistance to tick infestation, if prevalent in nature, may severely limit the spread of tick-borne viruses. Such an effect could result directly from a reduction in the number of ticks that acquire virus, or indirectly from poor egg production (in the case of viruses maintained in ticks by vertical transmission) and reduced survival of ticks fed on resistant hosts.


A practical solution for preserving single cells for RNA sequencing.
The design and implementation of single-cell experiments is often limited by their requirement for fresh starting material. We have adapted a method for histological tissue fixation using dithio-bis(succinimidyl propionate) (DSP), or Lomant's Reagent, to stabilise cell samples for single-cell transcriptomic applications. DSP is a reversible cross-linker of free amine groups that has previously been shown to preserve tissue integrity for histology while maintaining RNA integrity and yield in bulk RNA extractions. Although RNA-seq data from DSP-fixed single cells appears to be prone to characteristic artefacts, such as slightly reduced yield of cDNA and a detectable 3' bias in comparison with fresh cells, cell preservation using DSP does not appear to substantially reduce RNA complexity at the gene level. In addition, there is evidence that instantaneous fixation of cells can reduce inter-cell technical variability. The ability of DSP-fixed cells to retain commonly used dyes, such as propidium iodide, enables the tracking of experimental sub-populations and the recording of cell viability at the point of fixation. Preserving cells using DSP will remove several barriers in the staging of single-cell experiments, including the transport of samples and the scheduling of shared equipment for downstream single-cell isolation and processing.


FGF signaling regulates rod photoreceptor cell maintenance and regeneration in zebrafish.
Fgf signaling is required for many biological processes involving the regulation of cell proliferation and maintenance, including embryonic patterning, tissue homeostasis, wound healing, and cancer progression. Although the function of Fgf signaling is suggested in several different regeneration models, including appendage regeneration in amphibians and fin and heart regeneration in zebrafish, it has not yet been studied during zebrafish photoreceptor cell regeneration. Here we demonstrate that intravitreal injections of FGF-2 induced rod precursor cell proliferation and photoreceptor cell neuroprotection during intense light damage. Using the dominant-negative Tg(hsp70:dn-fgfr1) transgenic line, we found that Fgf signaling was required for homeostasis of rod, but not cone, photoreceptors. Even though fgfr1 is expressed in both rod and cone photoreceptors, we found that Fgf signaling differentially affected the regeneration of cone and rod photoreceptors in the light-damaged retina, with the dominant-negative hsp70:dn-fgfr1 transgene significantly repressing rod photoreceptor regeneration without affecting cone photoreceptors. These data suggest that rod photoreceptor homeostasis and regeneration is Fgf-dependent and that rod and cone photoreceptors in adult zebrafish are regulated by different signaling pathways.


Hollow SnO2 nanospheres with oxygen vacancies entrapped by a N-doped graphene network as robust anode materials for lithium-ion batteries.
The practical application of tin dioxide (SnO2) in lithium-ion batteries has been greatly hindered by its large volumetric expansion and low conductivity. Thus, a rational design of the size, geometry and the pore structure of SnO2-based nanomaterials is still a dire demand. To this end, herein we report an effective approach for engineering hollow-structured SnO2 nanospheres with adequate surface oxygen vacancies simultaneously wrapped by a nitrogen-doped graphene network (SnO2-x/N-rGO) through an electrostatic adsorption-induced self-assembly together with a thermal reduction process. The close electrostatic attraction achieved a tight and uniform combination of positively charged SnO2 nanospheres with negatively charged graphene oxide (GO), which can alleviate the aggregation and volume expansion of the entrapped SnO2 nanospheres. Subsequent thermal treatment not only ensures a significant reduction of the GO sheets accompanying nitrogen-doping, but also induces the generation of oxygen vacancies on the surface of the SnO2 hollow nanospheres, together building up a long-range and bicontinuous transfer channel for rapid electron and ion transport. Because of these structural merits, the as-built SnO2-x/N-rGO composite used as the anode material exhibits excellent robust cycling stability (∼912 mA h g-1 after 500 cycles at 0.5 A g-1 and 652 mA h g-1 after 200 cycles at 1 A g-1) and superior rate capability (309 mA h g-1 at 10 A g-1). This facile fabrication strategy may pave the way for the construction of high performance SnO2-based anode materials for potential application in advanced lithium-ion batteries.


The impact of shelter use and housing placement on mortality hazard for unaccompanied adults and adults in family households entering New York City shelters: 1990-2002.
This study examines mortality among New York City (NYC) homeless shelter users, assessing the relationships between mortality hazard and time in shelter, patterns of homelessness, and subsequent housing exits for both adults in families and single adults. Administrative records from the NYC shelter system were matched with death records from the Social Security Administration for 160,525 persons. Crude mortality rates and life tables were calculated, and survival analyses were undertaken using these data. Life expectancy was 64.2 and 68.6 years for single adult males and single adult females, respectively, and among adults in families, life expectancy was 67.2 and 70.1 years for males and females, respectively. For both groups, exits to stable housing (subsidized or non-subsidized) were associated with reduced mortality hazard. And while mortality hazard was substantially reduced for the time adults were in shelters, extended shelter use patterns were associated with increased mortality hazard. Differences between single homelessness and family homelessness extend to disparities in mortality rates. Although causal links cannot be established here, results suggest that, for both subgroups of the homeless population, prompt resolution of homelessness and availability of housing interventions may contribute to reduced mortality.


Experimental approaches towards interpreting dolphin-stimulated bioluminescence.
Flow-induced bioluminescence provides a unique opportunity for visualizing the flow field around a swimming dolphin. Unfortunately, previous descriptions of dolphin-stimulated bioluminescence have been largely anecdotal and often conflicting. Most references in the scientific literature report an absence of bioluminescence on the dolphin body, which has been invariably assumed to be indicative of laminar flow. However, hydrodynamicists have yet to find compelling evidence that the flow remains laminar over most of the body. The present study integrates laboratory, computational and field approaches to begin to assess the utility of using bioluminescence as a method for flow visualization by relating fundamental characteristics of the flow to the stimulation of naturally occurring luminescent plankton. Laboratory experiments using fully developed pipe flow revealed that the bioluminescent organisms identified in the field studies can be stimulated in both laminar and turbulent flow when shear stress values exceed approximately 0.1 N m-2. Computational studies of an idealized hydrodynamic representation of a dolphin (modeled as a 6:1 ellipsoid), gliding at a speed of 2 m s-1, predicted suprathreshold surface shear stress values everywhere on the model, regardless of whether the boundary layer flow was laminar or turbulent. Laboratory flow visualization of a sphere demonstrated that the intensity of bioluminescence decreased with increasing flow speed due to the thinning of the boundary layer, while flow separation caused a dramatic increase in intensity due to the significantly greater volume of stimulating flow in the wake. Intensified video recordings of dolphins gliding at speeds of approximately 2 m s-1 confirmed that brilliant displays of bioluminescence occurred on the body of the dolphin. The distribution and intensity of bioluminescence suggest that the flow remained attached over most of the body. A conspicuous lack of bioluminescence was often observed on the dolphin rostrum and melon and on the leading edge of the dorsal and pectoral fins, where the boundary layer is thought to be thinnest. To differentiate between effects related to the thickness of the stimulatory boundary layer and those due to the latency of the bioluminescence response and the upstream depletion of bioluminescence, laboratory and dolphin studies of forced separation and laminar-to-turbulent transition were conducted. The observed pattern of stimulated bioluminescence is consistent with the hypothesis that bioluminescent intensity is directly related to the thickness of the boundary layer.


Dose-response of female llamas to ovulation-inducing factor from seminal plasma.
The present study was designed to determine if the dose of purified ovulation-inducing factor (OIF) from llama seminal plasma required to provoke an ovulatory response is physiologically relevant in terms of the proportion present in a normal ejaculate and to test the hypothesis that corpus luteum (CL) form and function are affected by OIF in a dose-dependent manner. Female llamas were assigned randomly to five groups (n = 10 per group) and given a single i.m. dose of 500, 250, 125, or 60 μg of purified OIF (representative of the amount present in 1/25th to 1/200th of a normal ejaculate) or 1 ml of PBS (control). Ovulation and CL development were monitored by transrectal ultrasonography. Blood samples were taken to measure plasma progesterone concentrations and to determine changes in plasma concentrations of luteinizing hormone (LH). The high dose of OIF (500 μg) was associated with the highest incidence of ovulation (P < 0.05), the greatest maximum CL diameter (P < 0.05), and the largest day-to-day profiles of CL diameter (P < 0.05) and plasma progesterone concentrations (P < 0.01). A rise in plasma LH concentration was apparent in all llamas that ovulated and was most rapid and highest in the high-dose group (P < 0.01). The low dose of OIF (60 μg) was minimally effective for induction of ovulation and the least luteotrophic, as evidenced by the smallest maximum CL diameter and the smallest day-to-day profiles for CL diameter and plasma concentrations of progesterone and LH. Responses were intermediate for the middle-dose groups (125 and 250 μg). We conclude that OIF from llama seminal plasma has a dose-dependent effect on ovulation rate and CL form and function in llamas and that the biological effect of OIF is evident at physiologically relevant doses (i.e., as little as 1/100th of that present in an ejaculate).


High-speed particle detection and tracking in microfluidic devices using event-based sensing.
Visualising fluids and particles within channels is a key element of microfluidic work. Current imaging methods for particle image velocimetry often require expensive high-speed cameras with powerful illuminating sources, thus potentially limiting accessibility. This study explores for the first time the potential of an event-based camera for particle and fluid behaviour characterisation in a microfluidic system. Event-based cameras have the unique capacity to detect light intensity changes asynchronously and to record spatial and temporal information with low latency, low power and high dynamic range. Event-based cameras could consequently be relevant for detecting light intensity changes due to moving particles, chemical reactions or intake of fluorescent dyes by cells to mention a few. As a proof-of-principle, event-based sensing was tested in this work to detect 1 μm and 10 μm diameter particles flowing in a microfluidic channel for average fluid velocities of up to 1.54 m s-1. Importantly, experiments were performed by directly connecting the camera to a standard fluorescence microscope, only relying on the microscope arc lamp for illumination. We present a data processing strategy that allows particle detection and tracking in both bright-field and fluorescence imaging. Detection was achieved up to a fluid velocity of 1.54 m s-1 and tracking up to 0.4 m s-1 suggesting that event-based cameras could be a new paradigm shift in microscopic imaging.


Nursing Home Implementation of Health Information Technology: Review of the Literature Finds Inadequate Investment in Preparation, Infrastructure, and Training.
Health information technology (HIT) is increasingly adopted by nursing homes to improve safety, quality of care, and staff productivity. We examined processes of HIT implementation in nursing homes, impact on the nursing home workforce, and related evidence on quality of care. We conducted a literature review that yielded 46 research articles on nursing homes' implementation of HIT. To provide additional contemporary context to our findings from the literature review, we also conducted semistructured interviews and small focus groups of nursing home staff (n = 15) in the United States. We found that nursing homes often do not employ a systematic process for HIT implementation, lack necessary technology support and infrastructure such as wireless connectivity, and underinvest in staff training, both for current and new hires. We found mixed evidence on whether HIT affects staff productivity and no evidence that HIT increases staff turnover. We found modest evidence that HIT may foster teamwork and communication. We found no evidence that the impact of HIT on staff or workflows improves quality of care or resident health outcomes. Without initial investment in implementation and training of their workforce, nursing homes are unlikely to realize potential HIT-related gains in productivity and quality of care. Policy makers should consider creating greater incentives for preparation, infrastructure, and training, with greater engagement of nursing home staff in design and implementation.


The evolution of practical radiobiological modelling.
A summary of the key aspects of radiobiological modelling is provided, based on the theoretical and practical concepts of the linear quadratic model, which gradually replaced other numerical approaches. The closely related biological effective dose concept is useful in many clinical applications. Biological effective dose formulations in conventional photon-based radiotherapy continue to be developed, and can be extended to the now increasingly used proton and ion-beam therapy, to very low or high dose ranges, the dose rate effect, hypoxia and repopulation. Such established and new research developments will be of interest to clinicians, physicists and biologists to better understand the processes underlying radiotherapy and assist their collaborative efforts to make radiotherapy safer and more effective.


Influence of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants in rabbit calvaria.
Until recently, adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants were unknown. Hence, this study investigated the short- and long-term effects of a 7-day regimen of parecoxib and diclofenac sodium on osseointegration of dental implants in calvarial bone. Eighteen New Zealand White rabbits were randomly allocated into three groups (each n = 6): Control group with no postoperative pain killers (Group A), diclofenac group (Group B) and parecoxib group (Group C). In each animal, one dental implant was placed into the calvarial bone (total n = 18). Three rabbits from each group were sacrificed in Week 4. The other three rabbits from each group were sacrificed in Week 12 postoperatively. The implant together with the calvarial bone and dura mater was harvested and subjected to micro-computed tomography (micro-CT) and histomorphometric analysis. Quantitative analysis of micro-CT data and histomorphometric data neither revealed any statistically significant (P ≤ 0.05) differences between the three different groups related to osseointegration nor between different time points of observation. In rabbits, a 7-day regimen of appropriate doses of diclofenac sodium and parecoxib did not adversely affect osseointegration of dental implants and bone healing in calvaria, neither short nor long term (12 weeks).


Delinquency and peer acceptance in adolescence: a within-person test of Moffitt's hypotheses.
We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent behavior become less accepted. Participants were 4,359 adolescents from 14 communities in the PROSPER study, which assessed friendship networks and delinquency from 6th (M = 11.8 years) to 9th (M = 15.3 years) grade. We operationalized peer acceptance as number of nominations received (indegree centrality), attractiveness as a friend (adjusted indegree centrality), and network bridging potential (betweenness centrality) and tested the hypotheses with multilevel modeling. Contrary to Moffitt's hypothesis, persistently delinquent youths did not become more accepted between early and middle adolescence, and although abstainers were less accepted in early adolescence, they became more accepted over time. Results were similar for boys and girls; when differences occurred, they provided no support for Moffitt's hypotheses for boys and were opposite of her hypotheses for girls. Sensitivity analyses in which alternative strategies and additional data were used to identify persistently delinquent adolescents produced similar results. We explore the implications of these results for Moffitt's assertions that social mimicry of persistently antisocial adolescents leads to increases in delinquency and that social isolation leads to abstention. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Structure of the core of the type III secretion system export apparatus.
Export of proteins through type III secretion systems is critical for motility and virulence of many major bacterial pathogens. Three putative integral membrane proteins (FliP, FliQ, FliR) are suggested to form the core of an export gate in the inner membrane, but their structure, assembly and location within the final nanomachine remain unclear. Here, we present the cryoelectron microscopy structure of the Salmonella Typhimurium FliP-FliQ-FliR complex at 4.2 Å. None of the subunits adopt canonical integral membrane protein topologies, and common helix-turn-helix structural elements allow them to form a helical assembly with 5:4:1 stoichiometry. Fitting of the structure into reconstructions of intact secretion systems, combined with cross-linking, localize the export gate as a core component of the periplasmic portion of the machinery. This study thereby identifies the export gate as a key element of the secretion channel and implies that it primes the helical architecture of the components assembling downstream.


Professional Liability and Gynecology-Only Practice: ACOG Committee Opinion Summary, Number 790.
Fellows of the American College of Obstetricians and Gynecologists may choose to limit the scope of their practices to gynecology and, accordingly, may choose not to carry professional liability coverage for obstetrics. The American College of Obstetricians and Gynecologists considers early pregnancy care to be within the scope of gynecology and gynecologic practice. Liability insurers that provide coverage for gynecology-only practices should provide coverage for clinical practice activities that involve the management of first-trimester and early second-trimester pregnancy and its complications.


Post-bariatric abdominoplasty: our experience.
The fast increase in obesity has been followed by the growth in the demand for plastic surgery in formerly obese patients. The weight loss is accompanied by new dysfunctions and disorders of the outline of the body that affects the quality of life of the patient. Abdominoplasty is a cosmetic surgery procedure that aims to remove the excess of skin and the redundant fat. The aim of this paper was to analyze our experience in this field and to test how functional abdominoplasty improved quality of life in the operated patients. In our Unit from January 2012 to December 2014, 25 patients (18 women and 7 men, age: 24 - 79 years, mean: 51 years) underwent abdominoplastic surgery. Only at least six months after bariatric surgery the patients were eligible for functional abdominoplasty. Average weight of the patients before surgery was 83.5 kg (range 58 - 163 Kg); averege BMI was 31 (range 24.77 - 57). The average quantity of tissue removed was 1.765 Kg (range 250 g - 11,5 Kg). Minor complications rate was in agreement with the percentages reported in literature. No mortality and major complications have occurred in our series. The majority of patients undergoing post-bariatric abdominoplasty reported an improvement in the quality of life and psychological well-being. In our opinion, however, only a multidisciplinary (surgical, psychological, dietological) approach of the post-bariatric patient allows to maintain long-term aesthetic and functional results.


An analytical framework for estimating aquatic species density from environmental DNA.
Environmental DNA (eDNA) analysis of water samples is on the brink of becoming a standard monitoring method for aquatic species. This method has improved detection rates over conventional survey methods and thus has demonstrated effectiveness for estimation of site occupancy and species distribution. The frontier of eDNA applications, however, is to infer species density. Building upon previous studies, we present and assess a modeling approach that aims at inferring animal density from eDNA. The modeling combines eDNA and animal count data from a subset of sites to estimate species density (and associated uncertainties) at other sites where only eDNA data are available. As a proof of concept, we first perform a cross-validation study using experimental data on carp in mesocosms. In these data, fish densities are known without error, which allows us to test the performance of the method with known data. We then evaluate the model using field data from a study on a stream salamander species to assess the potential of this method to work in natural settings, where density can never be known with absolute certainty. Two alternative distributions (Normal and Negative Binomial) to model variability in eDNA concentration data are assessed. Assessment based on the proof of concept data (carp) revealed that the Negative Binomial model provided much more accurate estimates than the model based on a Normal distribution, likely because eDNA data tend to be overdispersed. Greater imprecision was found when we applied the method to the field data, but the Negative Binomial model still provided useful density estimates. We call for further model development in this direction, as well as further research targeted at sampling design optimization. It will be important to assess these approaches on a broad range of study systems.


Analysis of mortality in low-risk patients undergoing coronary artery bypass grafting.
The aims of this study were to determine the early mortality rate in low-risk coronary artery bypass graft (CABG) patients and examine the causes of death, to identify problems that could be avoided in future surgeries. All low-risk patients (EuroSCORE ≤ 2) who died after CABG were included. Their peri-operative information was meticulously studied by internal and independent external reviewers to identify causes of death, which were classified as: cardiac or non-cardiac; and a further division as: (1) non-preventable, (2) preventable (technical error), and (3) preventable (system error). Early mortality was 0.93% (24/2570). Eleven patients (45.8%) were classified as preventable deaths. In six of them the main problem was identified as graft thrombosis, which was secondary to a technical error of either the harvesting or anastomosis of the left internal mammarian artery. There were also five system errors identified as delays in the treatment of an identified and potentially reversible problem. Correction of technical and system errors, such as harvesting of the left internal mammarian artery, haemostasis during surgery, and establishing standard protocols for the transfer of patients from ward to intensive care units will eventually lead to improvement in both the quality of care and patient outcomes, even in low-risk groups.


Relationship of the Severity of Citrus Greasy Spot, Caused by Mycosphaerella citri, to Ascospore Dose, Epiphytic Growth, Leaf Age, and Fungicide Timing.
Greasy spot, caused by Mycosphaerella citri, produces leaf and fruit lesions and defoliates trees, resulting in reduced yields and fruit size. Techniques now available allow production of large numbers of ascospores and the quantification of epiphytic growth. The effects of ascospore dose, leaf age, and the timing of fenbuconazole sprays on epiphytic growth and disease severity was determined primarily on rough lemon seedlings in the greenhouse. Inoculation of leaves with 104 ascospores/ml resulted in rapid development of epiphytic growth and symptoms. At lower doses, epiphytic growth and symptoms developed more slowly and were less severe. There was a linear relationship between log10 of the ascospore dose and ratings of epiphytic growth and symptoms, and a linear relationship between the amount of epiphytic growth and symptom severity in greenhouse tests. On grapefruit trees treated with different fungicides in six field experiments, there also was a significant linear relationship between epiphytic growth of M. citri measured in August and symptom severity rated in February to March of the following year, but coefficients of determination were much lower than in greenhouse experiments. Leaf age from 10 to 60 days did not affect susceptibility of leaves to M. citri. Fenbuconazole applied up to 50 days prior to inoculation still reduced epiphytic growth and greasy spot severity under greenhouse conditions, but the postinoculation treatments were effective for only 30 days.


Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016.
This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study. The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs). There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens. Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.


Ruminal ciliated protozoa in bison.
Ruminal contents from 79 slaughtered bison and 2 ruminally cannulated bison were collected to obtain information on total numbers and species distribution of ciliated protozoa. The bison originated from numerous herds throughout the Great Plains and were grouped into three dietary categories: (i) only forage; (ii) forage with moderate levels of supplementation; and (iii) feedlot concentrate-silage diet. Total ciliate counts were highest in bison receiving grain supplementation (210.1 x 10(4)/g) and lowest in bison consuming only forage (27.1 x 10(4)/g). All protozoan species found in bison have been reported in domestic livestock, although Ophryoscolex sp., a relatively common protozoan in cattle, was detected at low concentrations in only eight bison. The uncommon holotrich Microcetus lappus was present in five bison in concentrations reaching 8.4% of the total ciliate population. Charonina ventriculi, another infrequently observed species, was present in 18 bison, with the highest concentrations in forage-fed animals. Thirty bison possessed a type B protozoan population, characterized by Epidinium sp., Eudiplodinium maggii, and Eudiplodinium bovis. Thirty-eight bison possessed a mixed A-B population, characterized by Polyplastron sp. coexisting with low numbers of Eudiplodinium maggii or Epidinium sp. or both. Thirteen bison possessed populations lacking any remnant type B ciliate species. At least 29 of the bison possessing Polyplastron sp. were known to have been in contact with cattle, whereas all bison isolated from cattle had type B populations. The reduction of type B populations in bison becomes increasingly likely as bison production expands into areas inhabited by domestic livestock.