Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives

Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM

Serology based disease status of Pakistani population infected with Hepatitis B virus

<p>Abstract</p> <p>Background</p> <p>The infection rate of hepatitis B virus is continuously increasing in Pakistan. Therefore, a comprehensive study of epidemiological data is the need of time.</p> <p>Methods</p> <p>A total of 1300 individuals were screened for HBV infection markers including HBsAg, anti-HBsAg, HBeAg and anti-HBcAg. The association of these disease indicators was compared with patients' epidemiological characteristics like age, socio-economic status and residential area to analyze and find out the possible correlation among these variables and the patients disease status.</p> <p>Results</p> <p>52 (4%) individuals were found positive for HBsAg with mean age 23.5 ± 3.7 years. 9.30%, 33.47% and 12% individuals had HBeAg, antibodies for HBsAg, and antibodies for HBcAg respectively. HBsAg seropositivity rate was significantly associated (<it>p </it>= 0.03) with the residing locality indicating high infection in rural areas. Antibodies titer against HBsAg decreased with the increasing age reflecting an inverse correlation.</p> <p>Conclusion</p> <p>Our results indicate high prevalence rate of Hepatitis B virus infection and nationwide vaccination campaigns along with public awareness and educational programs are needed to be practiced urgently.</p

A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

<p>Abstract</p> <p>Background</p> <p>Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU) where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care.</p> <p>Methods/Design</p> <p>GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors) and undertook satisfaction surveys for caregivers of patients treated in GMU.</p> <p>Discussion</p> <p>This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care, but also improved staff knowledge and satisfaction. The model may then be transposed across various locations and disciplines in the acute hospital where delirious patients could be sited.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN52323811">ISRCTN52323811</a></p

Functional Interactions between the erupted/tsg101 Growth Suppressor Gene and the DaPKC and rbf1 Genes in Drosophila Imaginal Disc Tumors

BACKGROUND: The Drosophila gene erupted (ept) encodes the fly homolog of human Tumor Susceptibility Gene-101 (TSG101), which functions as part of the conserved ESCRT-1 complex to facilitate the movement of cargoes through the endolysosomal pathway. Loss of ept or other genes that encode components of the endocytic machinery (e.g. synatxin7/avalanche, rab5, and vps25) produces disorganized overgrowth of imaginal disc tissue. Excess cell division is postulated to be a primary cause of these 'neoplastic' phenotypes, but the autonomous effect of these mutations on cell cycle control has not been examined. PRINCIPAL FINDINGS: Here we show that disc cells lacking ept function display an altered cell cycle profile indicative of deregulated progression through the G1-to-S phase transition and express reduced levels of the tumor suppressor ortholog and G1/S inhibitor Rbf1. Genetic reductions of the Drosophila aPKC kinase (DaPKC), which has been shown to promote tumor growth in other fly tumor models, prevent both the ept neoplastic phenotype and the reduction in Rbf1 levels that otherwise occurs in clones of ept mutant cells; this effect is coincident with changes in localization of Notch and Crumbs, two proteins whose sorting is altered in ept mutant cells. The effect on Rbf1 can also be blocked by removal of the gamma-secretase component presenilin, suggesting that cleavage of a gamma-secretase target influences Rbf1 levels in ept mutant cells. Expression of exogenous rbf1 completely ablates ept mutant eye tissues but only mildly affects the development of discs composed of cells with wild type ept. CONCLUSIONS: Together, these data show that loss of ept alters nuclear cell cycle control in developing imaginal discs and identify the DaPKC, presenilin, and rbf1 genes as modifiers of molecular and cellular phenotypes that result from loss of ept

Molecular epidemiology of Hepatitis B virus genotypes in Pakistan

<p>Abstract</p> <p>Background</p> <p>Eight genotypes of Hepatitis B virus designated A-H, have been known but in Pakistan, no such data is available on the prevalent HBV genotypes. Therefore, the subject study was conducted to determine HBV genotypes in the indigenous Pakistani population.</p> <p>Methods</p> <p>A total of 690 individuals were enrolled for HBV screening with EIA and nested PCR. Positive samples were further analyzed to determine HBV genotypes (A-F) by multiplex-PCR using type specific primers.</p> <p>Results</p> <p>110 (15.94%) individuals were positive for HBV, including 64% males and 36% females. Out of these, 66 samples (65.34%) were classified into genotype D, 27 (26.73%) were of genotype B while 5(4.95%) had genotype A. In 3 (2.98%) samples, multiple genotypes were detected (genotype A+B; 2(1.99%) and genotypes B+D; 1(0.99%). Nine (8.18%) samples remained untyable.</p> <p>Conclusion</p> <p>In Asia, genotypes B and C are the most prevalent but our study reveals that genotype D is predominant and HBV infection constitutes a significant health problem in Pakistan.</p

In patient stroke rehabilitation efficiency: Influence of organization of service delivery and staff numbers

<p>Abstract</p> <p>Background</p> <p>Outcomes of inpatient stroke rehabilitation need to be reviewed in terms of optimal resource utilization (staff time, service organization, and duration of stay). We compared FIM efficiency scores between three hospitals, and also variation in FIM scores over a ten year period in one hospital undergoing reduction in staff numbers, to examine the relationship between outcome and service characteristics.</p> <p>Method</p> <p>This is a retrospective study comparing the mean FIM efficiency for stroke patients (FIM score – FIM admission score) divided by duration of stay for 2005 among three rehabilitation hospitals adjusting for age and baseline FIM score, and a longitudinal study of changes in mean FIM efficiency during a ten year period in one hospital, to examine the effects of different service organization and staff numbers.</p> <p>Results</p> <p>FIM efficiency (FIMEG) was inversely associated with age, and positively associated with admission FIM score. FIMEG was higher in the hospital with a coordinated care plan involving medical, nursing, occupational, physiotherapy staff and other healthcare providers working as a team, with a seamless interface with community rehabilitation services. Over a ten year period, reduction in staff numbers was associated with reduction in FIMEG, which may be offset to some extent by service re-engineering.</p> <p>Conclusion</p> <p>Within hospital organization of stroke rehabilitation services may influence outcome. A critical number of staff may be identified for the provision of services, below which rehabilitation efficiency may be affected.</p

Skeletal muscle gene expression in response to resistance exercise: sex specific regulation

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms underlying the sex differences in human muscle morphology and function remain to be elucidated. The sex differences in the skeletal muscle transcriptome in both the resting state and following anabolic stimuli, such as resistance exercise (RE), might provide insight to the contributors of sexual dimorphism of muscle phenotypes. We used microarrays to profile the transcriptome of the biceps brachii of young men and women who underwent an acute unilateral RE session following 12 weeks of progressive training. Bilateral muscle biopsies were obtained either at an early (4 h post-exercise) or late recovery (24 h post-exercise) time point. Muscle transcription profiles were compared in the resting state between men (n = 6) and women (n = 8), and in response to acute RE in trained exercised vs. untrained non-exercised control muscle for each sex and time point separately (4 h post-exercise, n = 3 males, n = 4 females; 24 h post-exercise, n = 3 males, n = 4 females). A logistic regression-based method (LRpath), following Bayesian moderated t-statistic (IMBT), was used to test gene functional groups and biological pathways enriched with differentially expressed genes.</p> <p>Results</p> <p>This investigation identified extensive sex differences present in the muscle transcriptome at baseline and following acute RE. In the resting state, female muscle had a greater transcript abundance of genes involved in fatty acid oxidation and gene transcription/translation processes. After strenuous RE at the same relative intensity, the time course of the transcriptional modulation was sex-dependent. Males experienced prolonged changes while females exhibited a rapid restoration. Most of the biological processes involved in the RE-induced transcriptional regulation were observed in both males and females, but sex specificity was suggested for several signaling pathways including activation of notch signaling and TGF-beta signaling in females. Sex differences in skeletal muscle transcriptional regulation might implicate a mechanism behind disproportional muscle growth in males as compared with female counterparts after RE training at the same relative intensity.</p> <p>Conclusions</p> <p>Sex differences exist in skeletal muscle gene transcription both at rest and following acute RE, suggesting that sex is a significant modifier of the transcriptional regulation in skeletal muscle. The findings from the present study provide insight into the molecular mechanisms for sex differences in muscle phenotypes and for muscle transcriptional regulation associated with training adaptations to resistance exercise.</p

Diagnoses, problems and healthcare interventions amongst older people with an unscheduled hospital admission who have concurrent mental health problems: a prevalence study

Background Frail older people with mental health problems including delirium, dementia and depression are often admitted to general hospitals. However, hospital admission may cause distress, and can be associated with complications. Some commentators suggest that their healthcare needs could be better met elsewhere. Methods We studied consecutive patients aged 70 or older admitted for emergency medical or trauma care to an 1800 bed general hospital which provided sole emergency medical and trauma services for its local population. Patients were screened for mental health problems, and those screening positive were invited to take part. 250 participants were recruited and a sub-sample of 53 patients was assessed by a geriatrician for diagnoses, impairments and disabilities, healthcare interventions and outstanding needs. Results Median age was 86 years, median Mini-Mental State Examination score at admission was 16/30, and 45% had delirium. 19% lived in a care home prior to admission. All the patients were complex. A wide range of main admission diagnoses was recorded, and these were usually complicated by falls, immobility, pain, delirium, dehydration or incontinence. There was a median of six active diagnoses, and eight active problems. One quarter of problems was unexplained. A median of 13 interventions was recorded, and a median of a further four interventions suggested by the geriatrician. Those with more severe cognitive impairment had no less medical need. Conclusions This patient group, admitted to hospital in the United Kingdom, had numerous healthcare problems, and by implication, extensive healthcare needs. Patients with simpler conditions were not identified, but may have already been rapidly discharged or redirected to non-hospital services by the time assessments were made. To meet the needs of this group outside the hospital would need considerable investment in medical, nursing, therapy and diagnostic facilities. In the meantime, acute hospitals should adapt to deliver comprehensive geriatric assessment, and provide for their mental health needs