Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Discrete Work Shifts on a Nonterminating Service System

Hospital emergency departments (EDs) provide around‐the‐clock medical care, and as such are generally modeled as nonterminating queues. However, from the care provider's point of view, ED care is not a never‐ending process, but rather occurs in discrete work shifts and may require passing unfinished work to the next care provider at the end of the shift. We use data from a large, academic medical center ED to show that the patients’ rate of service completion varies over the course of the physician shift. Furthermore, patients that have experienced a physician handoff have a higher rate of service completion than nonhanded off patients. As a result, a patient's expected treatment time is impacted by when the physician's shift treatment begins. We also show that patients that have been handed off are more likely to revisit the ED within three days, suggesting that patient handoffs lower clinical quality. Lastly, we use simulation to show that shift length and new‐patient cutoff rules can be used to reduce handoffs, but at the expense of system throughput.
Regulation of adenosine receptors expression in rat B lymphocytes by insulin

Development of diabetes is associated with altered expression of adenosine receptors (ARs). Some of these alterations might be attributed to changes in insulin concentration. This study was undertaken to investigate the possible insulin effect on ARs level, and to determine the signaling pathway utilized by insulin to regulate the expression of ARs in rat B lymphocytes. Western blot analysis of B lymphocytes protein extracts indicated that all four ARs were present at detectable levels in the cells cultured for 24 h without insulin (≤10−11 M), although the protein band of A2A‐AR was barely visible. Inclusion of insulin (10−8 M) in the culture medium resulted in an increase of A1‐AR and A2A‐AR protein levels and a significant decrease of A2B‐AR protein, whereas the protein level of A3‐AR remained unchanged. Alterations in the ARs protein content were accompanied by changes in the ARs mRNA levels. Increase of the insulin concentration from 10−11 to 10−8 M resulted in 50% decrease of A2B‐AR mRNA level and two‐, and threefold increase of A1‐AR and A2A‐AR mRNA levels, respectively. Pretreatment of B cells with cycloheximide completely blocked the insulin action on A1‐AR and A2A‐AR mRNA, but not on A2B‐AR expression. Detailed pharmacological analysis demonstrated that insulin‐induced A1‐AR and A2A‐AR mRNA expression through the Ras/Raf‐1/MEK/ERK pathway. The insulin effect on A2B‐AR expression was blocked by p38 MAP kinase inhibitor (SB 203580). Concluding, elevated insulin concentration differentially affects the expression of ARs in B lymphocytes in a fashion that might enhance the various immunomodulatory effects of adenosine. J. Cell. Biochem. 109: 396–405, 2010. © 2009 Wiley‐Liss, Inc.
The significance of bowel permeability

Purpose of reviewIn clinical research, increased permeability has been scrutinized as a potential indicator of the severity of gastrointestinal disease and as a potential cause of the perpetuation of severe inflammatory activity in infectious states. This review discusses old and recent epidemiological and clinical evidence to establish whether increased permeability in sepsis is a sequel or a cause of multiple organ failure. In addition, old and new evidence linking inflammation and permeability in abnormal gastrointestinal anatomy and function to liver abnormalities in susceptible patients will be reviewed. Recent findingsIntestinal permeability has been found to be increased in several gastrointestinal diseases but not to be a very good marker of the severity of disease. Evidence is put forward supporting the claim that increased intestinal permeability is part of generalized leakiness of tight junctions in multiple organ failure and to play a less strong role as a primary event in its pathogenesis. Endemic malnutrition has been shown to be caused by interplay between malnutrition and intestinal inflammation. Recently experimental evidence has been put forward suggesting that enteral fat has anti-inflammatory effects on the intestine via the autonomic nervous system. Old clinical and new epidemiological evidence links intestinal inflammation, disruption of the enterohepatic cycle of bile acids, and liver disease. SummaryThe implications of the described findings are that inflammatory activity, locally induced by abnormal intestinal anatomy and disruption of the bile acid pool, or systemically by severe and uncontrolled inflammation/infection, should be the focus of treatment or research. In addition, the connection between intestinal inflammation and liver disease should be investigated.
Aberrant IgG isotype generation in mice with abnormal behaviors

Abstract BTBR T+tf/J (BTBR) mice were recently cited as a suitable animal model for the study of autism because of their behavioral characteristics and immunological changes similar to those reported from autistic subjects. The BTBR mouse was reported to have significantly higher levels of serum IgG, brain IgG deposits and anti-brain IgG than highly social C57BL/6 mice, suggesting involvement of aberrant immune responses in the occurrence of autism. Up-regulation of IgG production was investigated here, with a focus on the pattern of IgG isotype distribution compared with that in FVB/NJ (FVB) mice, another highly social control strain. The results indicated that levels of serum IgG1, IgG2b and IgG3 in post-natal day 21 BTBR mice was significantly higher than FVB mice, regardless of sex, resulting in higher IgG1:IgG2a ratios in BTBR mice than in FVB mice (statistical significance in males). A similar outcome regarding the IgG1:IgG2a ratio was observed in culture supernatants of bone marrow cells from these hosts. A presence of brain-reactive IgG in the sera of BTBR was higher than in FVB mice; levels of brain-reactive IgG against whole brain homogenates were higher in BTBR than in FVB mice, with significant differences seen in the striatum and substantia nigra regions. Levels of IgG1 deposited in the cerebellum, cortex, hippocampus or striatum of both BTBR male and female mice were significantly higher than in FVB counterparts. Overall, these results suggest that alterations in IgG isotype production or deposition in the brain could be implicated in the aberrant immune reactivities of BTBR mice.
Feasibility of proton pencil beam scanning treatment of free-breathing lung cancer patients

Abstract Background: The interplay effect might degrade the dose of pencil beam scanning proton therapy to a degree that free-breathing treatment might be impossible without further motion mitigation techniques, which complicate and prolong the treatment. We assessed whether treatment of free-breathing patients without motion mitigation is feasible. Material and methods: For 40 lung cancer patients, 4DCT datasets and individual breathing patterns were used to simulate 4D dynamic dose distributions of 3D treatment plans over 33 fractions delivered with an IBA universal nozzle. Evaluation was done by assessing under- and overdosage in the target structure using the parameters V90, V95, V98, D98, D2, V107 and V110. The impact of using beam-specific target volumes and the impact of changes in motion and patient anatomy in control 4DCTs were assessed. Results: Almost half of the patients had tumour motion amplitudes of less than 5 mm. Under- and overdosage was significantly smaller for patients with tumour motion below 5 mm compared to patients with larger motion (2% vs. 13% average absolute reduction of V95, 2% vs. 8% average increase in V107, p < .01). Simulating a 33-fraction treatment, the dose degradation was reduced but persisted for patients with tumour motion above 5 mm (average ΔV95 of <1% vs. 3%, p < .01). Beam-specific target volumes reduced the dose degradation in a fractionated treatment, but were more relevant for large motion. Repeated 4DCT revealed that changes in tumour motion during treatment might result in unexpected large dose degradations. Conclusion: Tumour motion amplitude is an indicator of dose degradation caused by the interplay effect. Fractionation reduces the dose degradation allowing the unmitigated treatment of patients with small tumour motions of less than 5 mm. The beam-specific target approach improves the dose coverage. The tumour motion and position needs to be assessed during treatment for all patients, to quickly react to possible changes, which might require treatment adaptation.
Predicting portal hypertension as assessed by acoustic radiation force impulse: correlations with the Doppler ultrasound.

OBJECTIVE The purpose of this study was to assess the value of acoustic radiation force impulse (ARFI) for evaluating portal hypertension by correlating the elasticity of liver cirrhosis, as measured by ARFI, with haemodynamic indices measured by Doppler ultrasound. METHODS We evaluated the data of a total of 154 prospectively enrolled patients who underwent both duplex Doppler ultrasound and ARFI imaging. The duplex Doppler ultrasound indices, including the mean portal vein velocity, splenic index (SI) and splenoportal index (SPI) were evaluated to determine the statistical correlation with shear wave velocity (SWV) of ARFI. We also analysed the differences in the correlations between the SI, SPI and SWV of the group who had varices. The correlations were assessed with Spearman's rank correlation coefficients. RESULTS There was an increase of SWV in parallel with the increase of the SI (ρ=0.409, p<0.01) and SPI (ρ=0.451, p<0.01). In the patient group who did not have varices (n=74), the Doppler indices were found to be more correlated with the SWV (SI: ρ=0.447, SPI: ρ=0.552, p<0.01). However, the group with varices showed no correlation between the SWV and the Doppler parameters. CONCLUSION SWV of ARFI was well correlated statistically with Doppler parameters, but is of limited value in predicting portal hypertension directly owing to great variability of Doppler parameters. By evaluating the correlation between ARFI and Doppler ultrasound, we suggest that the SWV might be a non-invasive supplementary tool for predicting portal hypertension.
Short‐Chain Fatty Acids Induce Pro‐Inflammatory Cytokine Production Alone and in Combination with Toll‐Like Receptor Ligands

Citation Mirmonsef P, Zariffard MR, Gilbert D, Makinde H, Landay, AL, Spear GT. Short‐chain fatty acids induce pro‐inflammatory cytokine production alone and in combination with Toll‐like receptor ligands. Am J Reprod Immunol 2012; 67: 391–400
Emerging Trend in the Culture of Domestic Violence against Men in Southern Nigeria Barr.

Hitherto domestic violence was seen as one perpetrated by men against women and that men were not in any way victims of domestic violence. Recent studies indicate that intimate partner violence in Nigeria is no longer a rarity but a reality with varying degrees of implications on the individuals and the society at large. The society therefore through the use of both quantitative and qualitative research technique sought to investigate the existence of domestic violence against men and the motives behind their occurrences. Delta and Edo States in Southern Nigeria were chosen as the study area while respondents were randomly selected from the state capitals of Benin and Asaba respectively. With the aid of snowballing sampling method, in-depth interviews were conducted on some respondents. The findings of the study revealed that domestic violence against men exists in Nigeria and the motives range from self-defence, provocation, infidelity, financial hardship and drunkenness. The study therefore suggests that government agencies, civil societies and religious bodies should do more advocacies on its reality and impact on homes and the society while law enforcement agents should be alive to their responsibility.
Renal Disease in Adults With TSC2/PKD1 Contiguous Gene Syndrome

The most common renal lesions of tuberous sclerosis complex, an autosomal-dominant syndrome resulting from losses of TSC1 (9q34) or TSC2 (16p13.3), are renal cysts and angiomyolipomas. Epithelial neoplasms are less common. The TSC2 gene lies adjacent to PKD1, the major gene responsible for autosomal-dominant polycystic kidney disease. Recently, a deletion mutation disrupting both TSC2 and PKD1 has been described in young children with tuberous sclerosis complex with severe renal cystic disease. This disease has been termed the TSC2/PKD1 contiguous gene syndrome. We describe the lesions in the resected kidneys of two adults with TSC2/PDK1 contiguous gene syndrome, at the time of the nephrectomies: a 31-year-old man and his 44-year-old mother. The four kidneys were enlarged reniform masses composed of cysts lined by flattened, cuboidal, or, infrequently, large deeply eosinophilic epithelial cells. The kidneys also contained numerous classic angiomyolipomas and rare intraglomerular microlesions. In the son the largest tumor was a monotypic epithelioid angiomyolipoma. In the wall of his left renal pelvis there was a plaque-shaped, HMB-45-positive localized lesion of lymphangioleiomyomatosis. This is the first description of the renal lesions in adults with genetically confirmed TSC2/PDK1 contiguous gene syndrome. The pathologic findings highlight the importance of thorough sampling for histology in polycystic kidney diseases and indicate that the observation of an angiomyolipoma in biopsy material from patients with enlarged cystic kidneys should suggest the diagnosis of TSC2/PKD1 contiguous gene syndrome, even in cases without ultrasonographic and macroscopic evidence of angiomyolipoma.
ICT and Empowerment of Rural and Deprived Women in Asia

The Role of Information and Communications Technologies (ICTs) as a tool for development has attracted the sustained attention of the government and NGOs. The millennium declaration adopted in 2000 underscored the urgency of ensuring that the benefits of new technologies, especially ICTs, are made available to all. ICTs can be a powerful catalyst for political and social empowerment of women and the promotion of gender equality (United Nations 2005:3). This paper examines some key ICT ‐ based initiatives in Asia in general and India in particular which are specifically designed for the empowerment of rural and deprived women. It shows how ICT ‐ based initiatives empower rural and deprived women; it tries to clarify a theoretical dilemma between meaning and measurement of empowerment and provides a holistic definition of empowerment. Finally it focuses on the twofold need to address some of the social and technical challenges as well as policy suggestions to use ICTs proactively and effectively to promote gender equality and for the empowerment of rural and deprived women. The study used observations, focus group discussions and review of documents to collect secondary and primary data.
Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia

Objective: To investigate the possible synergistic effect of microvascular lesions with mild Alzheimer disease (AD) pathology in mixed cases. Methods: We assessed the cognitive impact of cortical microinfarcts, deep white matter and periventricular demyelination, as well as diffuse and focal gliosis in a large series of 43 prospectively evaluated autopsy cases scored Braak neurofibrillary tangle stage III, but without macroscopic vascular pathology or substantial non-AD, nonvascular microscopic lesions. We included bilateral assessment of all types of microvascular lesions and used multivariate models that control for the possible confounding effect of age and amyloid β-protein (Aβ) deposits. Results: Only cortical microinfarcts and periventricular demyelination were significantly associated with the Clinical Dementia Rating Scale (CDR) score. In a univariate model, the cortical microinfarct score explained 9% of the variability in CDR scores and periventricular demyelination score 7.3%. Aβ deposition explained only 3.5% of the CDR variability. In a logistic regression model, both variables were strongly associated with the presence of dementia (R = 0.45; p < 0.05). When the CDR sum of the boxes was used, Aβ staging explained 8.9% of cognitive variability, the addition of cortical microinfarct predicted an extra 15.5%, and that of periventricular demyelination an extra 9%. Conclusions: Cortical microinfarcts and, to a lesser degree, periventricular demyelination contribute to the cognitive decline in individuals at high risk for dementia. Both should be taken into account when defining the neuropathologic criteria for mixed dementia.
Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

Deciphering Hepatitis C Hepatitis C virus is a major cause of liver disease and cancer. Two envelope glycoproteins, E1 and E2, form a heterodimer that facilitates infection. The envelope proteins have been difficult to crystallize, hindering vaccine development. Kong et al. (p. 1090) designed an E2 core glycoprotein construct and solved the crystal structure of the glycosylated protein in complex with a broadly neutralizing antibody. The host cell receptor binding site was identified by electron microscopy and mutagenesis. The findings should help in future drug and vaccine design. The structure of a key viral surface protein provides insight for drug and vaccine development. Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.
Combination of genetic and quantitative serological immune markers are associated with complicated Crohn's disease behavior

Background: Treatment of Crohn's disease (CD) with biologics may alter disease progression, leading to fewer disease‐related complications, but cost and adverse event profiles often limit their effective use. Tools identifying patients at high risk of complications, who would benefit the most from biologics, would be valuable. Previous studies suggest that biomarkers may aid in determining the course of CD. We aimed to determine if combined serologic immune responses and NOD2 genetic markers are associated with CD complications. Methods: In this cross‐sectional study, banked blood from well‐characterized CD patients (n = 593; mean follow‐up: 12 years) from tertiary and community centers was analyzed for six serological biomarkers (ASCA‐IgA, ASCA‐IgG, anti‐OmpC, anti‐CBir1, anti‐I2, pANCA). In a patient subset (n = 385), NOD2 (SNP8, SNP12, SNP13) genotyping was performed. Complications included stricturing and penetrating disease behaviors. A logistic regression model for the risk of complications over time was constructed and evaluated by cross‐validation. Results: For each serologic marker, complication rates were stratified by quartile. Complication frequency was significantly different across quartiles for each marker (P trend ≤ 0.001). Patients with SNP13 NOD2 risk alleles experienced increased complications versus patients without NOD2 mutations (P ≤ 0.001). A calibration plot of modeled versus observed complication rates demonstrated good agreement (R = 0.973). Performance of the model integrating serologic and genetic markers was demonstrated by area under the receiver operating characteristic curve (AUC = 0.801; 95% confidence interval: 0.757–0.846). Conclusions: This model combining serologic and NOD2 genetic markers may provide physicians with a tool to assess the probability of patients developing a complication over the course of CD.
Coronary Heart Disease Risk Reduction Intervention Among Overweight Smokers with a Psychotic Disorder: Pilot Trial

Objective: The aim of the present pilot study was to test the feasibility and short-term impact of a multi-component risk factor intervention for reducing (i) coronary heart disease (CHD) risk; (ii) smoking; and (iii) weight among smokers with psychosis. Secondary dependent variables included physical activity, unhealthy eating, substance use, psychiatric symptomatology, treatment retention, general functioning, and quality of life. Method: This was a feasibility study utilizing a pre–post-treatment design with no control group (n=43). All participants provided written informed consent and were assessed before treatment and again a mean of 19.6weeks later. The treatment consisted of nine individual 1h sessions of motivational interviewing and cognitive behaviour therapy plus nicotine replacement therapy, in addition to treatment as usual. Research assistants who had not been involved in the delivery of the treatment programme conducted post-treatment assessments. Results: The intervention was associated with significant reductions in CHD risk scores, smoking and weight. A significant improvement was also reported in level of moderate physical activity, and a small change in the unhealthy eating index was reported. No improvement in biological measures (cholesterol and blood pressure) was evident. Conclusions: A multi-component CHD risk factor intervention among smokers with psychosis appears to be feasible and effective in the short-term. A randomized controlled trial replicating and extending these findings is warranted.
Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery.

PURPOSE Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center. PATIENTS AND METHODS Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types. RESULTS A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P < .0001) and relapse-predicting (P < .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation. CONCLUSION The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.