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Background Salmonella enterica serovar Typhi ( Salmonella Typhi) is the cause of typhoid fever. Salmonella Typhi may be transmitted through shedding in the stool, which can continue after recovery from acute illness. Shedding is detected by culturing stool, which is challenging to co-ordinate at scale. We hypothesised that sero-surveillance would direct us to those shedding Salmonella Typhi in stool following a typhoid outbreak. Methods In 2016 a typhoid outbreak affected one in four residents of a Nursing School in Malosa, Malawi. The Department of Health asked for assistance to identify nursing students that might spread the outbreak to other health facilities. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d) three and six months after the outbreak. We selected participants in the highest and lowest deciles for anti-Vi IgG titre (measured at visit one) and obtained stool for Salmonella culture and PCR. All participants reported whether they had experienced fever persisting for three days or more during the outbreak (in keeping with the WHO definitions of ‘suspected typhoid’). We tested for salmonellae in the Nursing School environment. Results We obtained 320 paired serum samples from 407 residents. We cultured stool from 25 residents with high anti-Vi IgG titres and 24 residents with low titres. We did not recover Salmonella Typhi from stool; four stool samples yielded non-typhoidal salmonellae; one sample produced a positive PCR amplification for a Salmonella Typhi target. Median anti-Vi and anti-H:d IgG titres fell among participants who reported persistent fever. There was a smaller fall in anti-H:d IgG titres among participants who did not report persistent fever. Non-typhoidal salmonellae were identified in water sampled at source and from a kitchen tap. Conclusion High titres of anti-Vi IgG did not identify culture-confirmed shedding of Salmonella Typhi. There was a clear serologic signal of recent typhoid exposure in the cohort, represented by waning IgG antibody titres over time. The presence of non-typhoidal salmonellae in drinking water indicates sub-optimal sanitation. Developing methods to detect and treat shedding remains an important priority to complement typhoid conjugate vaccination in efforts to achieve typhoid elimination.

The conflict environment in Libya is characterized by continued pervasive insecurity amidst the widespread availability of small arms and light weapons (SALW). After the First Civil War, armed brigades took the law into their own hands and the resulting violence terminated a short-lived post-conflict period that has relapsed into a Second Civil War. The Libyan government has struggled to assert authority over armed groups and these brigades, refusing to disarm have contributed directly the initiation of a second conflict; some are motivated by self-defense, status, criminality, vindication or political aims. Once, a bastion of public health in the Middle East and North Africa (MENA), the country now faces a substantial and unprecedented challenge: to rebuild a devastated health system amidst the burden of armed violence and the proliferation of small and light weapons (SALW) especially firearms of various kinds. The health system in Libya is compromised; healthcare professionals have little time to record or document such cases given the immediate clinical needs of the patient. This corresponding decreased capacity to deal with an increasing demand on services caused by SALW-related morbidity compounds the challenge of data collection and indicates that external support and advocacy are required. A public health strategy towards effective SALW armed violence reduction and injury prevention requires the interdisciplinary advocacy of practitioners across the fields of justice, security, development, health and education. Through surveillance of firearms and injuries in the post-conflict environment we can better evaluate and respond to the burden of armed violence in Libya. In order to reduce armed a reconceptualisation of arms reduction campaigns must occur. Notable emerging evidence recommends the inclusion of community-based interventions and development programs which address local motivations for firearms ownership alongside improved international coordination. This renewed approach holds importance for recovery, development and securing the transition to peace. The high prevalence of firearm ownership, weak institutions, nascent security forces, porous borders, inadequate weapons stockpiles, combined with high military spending, compounds public weaponisation as a health crisis for the entire MENA region.

Background Capacity building partnerships between healthcare institutions have the potential to benefit both partners particularly in staff development. Previous research suggests that volunteering can contribute to professional development but there is little evidence on how learning is acquired, the barriers and facilitators to learning in this context or the process of translation of learning to the home environment. Results Volunteers from a healthcare partnership between the UK and Somaliland reported learning in communication, interdisciplinary working, teaching, management, leadership and service development. This learning came from observing familiar practices in unfamiliar environments; alternative solutions to familiar problems; learning about Somali culture; opportunities to assume higher levels of responsibility and new professional relationships. There was variability in the extent of translation to NHS practice. Time and support available for reflection and mentoring were important facilitators of this process. Conclusions The professional development outcomes documented in this study came directly from the experience of volunteering. Experiential learning theory suggests that this requires a complex process of critical reflection and new knowledge generation, testing and translation for use in new contexts. This process benefits from identification of learning as an important element of volunteering and support for reflection and the translation translation of learning to UK contexts. We suggest that missed opportunities for volunteer learning will remain until the volunteering process is overtly framed as part of continuing professional development.

Post-operative fever is common following emergency surgery. Investigation and management of post-operative fever can be challenging when a clear source of sepsis is not evident or the underlying source of infection is not recognised. We herein report a case of secondary pulmonary tuberculosis presenting as post-operative fever following emergency laparotomy for a perforated duodenal ulcer. This case of tuberculosis was diagnosed on day 41 post-operatively and prior inconclusive results meant that we relied mainly on re-visiting history and examination in order to identify 3 targeted investigations: plain chest X-ray, sputum sample and blood test. Accordingly, the co-management of this complex patient achieved a good outcome.

The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an \"obesogenic\" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

Objectives To assess the diagnostic accuracy of fast acquisition MRI in suspected cases of paediatric appendicitis presenting to a tertiary referral hospital. Materials and methods A prospective study was undertaken between May and October 2017 of 52 children who presented with suspected appendicitis and were referred for an abdominal ultrasound. All patients included in this study received both an abdominal ultrasound and five-sequence MRI consisting of axial and coronal gradient echo T2 scans, fat-saturated SSFSE and a diffusion-weighted scan. Participants were randomised into groups of MRI with breath-holds or MRI with free breathing. A patient satisfaction survey was also carried out. Histopathology findings, where available, were used as a gold standard for the purposes of data analysis. Statistical analysis was performed, and p values < 0.05 were considered statistically significant. Results Ultrasound had a sensitivity and specificity of 25% and 92.9%, respectively. MRI with breath-hold had a sensitivity and specificity of 81.8% and 66.7%, respectively, whilst MRI with free breathing was superior with sensitivity and specificity of 92.3% and 84.2%, respectively. MRI with free breathing was also more time efficient ( p < 0.0001). Group statistics were comparable ( p < 0.05). Conclusions The use of fast acquisition MRI protocols, particularly free breathing sequences, for patients admitted with suspected appendicitis can result in faster diagnosis, treatment and discharge. It also has a statistically significant diagnostic advantage over ultrasound. Additionally, the higher specificity of MR can reduce the number of negative appendectomies performed in tertiary centres.

Pharmacogenomics is yet to fulfill its promise of manifestly altering clinical medicine. As one example, a predictive test for tardive dyskinesia (TD) (an adverse drug reaction consequent to antipsychotic exposure) could greatly improve the clinical treatment of schizophrenia but human studies are equivocal. A complementary approach is the mouse-then-human design in which a valid mouse model is used to identify susceptibility loci, which are subsequently tested in human samples. We used inbred mouse strains from the Mouse Phenome Project to estimate the heritability of haloperidol-induced activity and orofacial phenotypes. In all, 159 mice from 27 inbred strains were chronically treated with haloperidol (3 mg kg −1 per day via subdermal slow-release pellets) and monitored for the development of vacuous chewing movements (VCMs; the mouse analog of TD) and other movement phenotypes derived from open-field activity and the inclined screen test. The test battery was assessed at 0, 30, 60, 90 and 120 days in relation to haloperidol exposure. As expected, haloperidol caused marked changes in VCMs, activity in the open field and extrapyramidal symptoms (EPS). Unexpectedly, factor analysis demonstrated that these measures were imprecise assessments of a latent construct rather than discrete constructs. The heritability of a composite phenotype was ∼0.9 after incorporation of the longitudinal nature of the design. Murine VCMs are a face valid animal model of antipsychotic-induced TD, and heritability estimates from this study support the feasibility of mapping of susceptibility loci for VCMs.

Tardive dyskinesia (TD) is a debilitating, unpredictable, and often irreversible side effect resulting from chronic treatment with typical antipsychotic agents such as haloperidol. TD is characterized by repetitive, involuntary, purposeless movements primarily of the orofacial region. In order to investigate genetic susceptibility to TD, we used a validated mouse model for a systems genetics analysis geared toward detecting genetic predictors of TD in human patients. Phenotypic data from 27 inbred strains chronically treated with haloperidol and phenotyped for vacuous chewing movements were subject to a comprehensive genomic analysis involving 426,493 SNPs, 4,047 CNVs, brain gene expression, along with gene network and bioinformatic analysis. Our results identified ~50 genes that we expect to have high prior probabilities for association with haloperidol-induced TD, most of which have never been tested for association with human TD. Among our top candidates were genes regulating the development of brain motor control regions (Zic4 and Nkx6-1), glutamate receptors (Grin1 and Grin2a), and an indirect target of haloperidol (Drd1a) that has not been studied as well as the direct target, Drd2.