West Heath Hospital

New neurons continue to be generated in the dentate gyrus throughout life, providing this region of the hippocampus with exceptional structural plasticity, but the function of this ongoing neurogenesis is unknown. Inhibition of adult neurogenesis produces some behavioral impairments that suggest a role for new neurons in learning and memory; however, other behavioral changes appear inconsistent with this function. A review of studies investigating the function of the hippocampus going back several decades reveals many ideas that seem to converge on a critical role for the hippocampus in stress response and emotion. These potential hippocampal functions provide new avenues for investigating the behavioral functions of adult neurogenesis. And, conversely, studies in animals lacking adult neurogenesis, which are likely to have more limited and more specific impairments than are seen with lesions, may provide valuable new insights into the function of the hippocampus. A complete understanding of the function of the hippocampus must explain its role in emotion and the relationship between its emotional and memory functions.

The field of molecular ecology has expanded enormously in the past two decades, largely because of the growing ease with which neutral molecular genetic data can be obtained from virtually any taxonomic group. However, there is also a growing awareness that neutral molecular data can provide only partial insight into parameters such as genetic diversity, local adaptation, evolutionary potential, effective population size, and taxonomic designations. Here we review some of the applications of neutral versus adaptive markers in molecular ecology, discuss some of the advantages that can be obtained by supplementing studies of molecular ecology with data from non-neutral molecular markers, and summarize new methods that are enabling researchers to generate data from genes that are under selection.

This study was undertaken to determine whether adaptation to 12 months of intense endurance exercise training could alter the relationship between the product of heart rate and systolic blood pressure (double product) and the extent of ischemic ST-segment depression during exercise in patients with coronary artery disease. True (i.e., not symptom-limited) maximum oxygen uptake capacity increased from 25.5 +/- 4.2 ml/kg/min (mean +/- SD) to 35.3 +/- 4.4 ml/Kg/min with training. The maximum degree of ST-segment depression during exercise averaged 0.20 +/- 0.04 mV before and 0.16 +/- 0.08 mV after training despite a 20% increase in maximum double product. The double product at which ST depression (0.1 mV) first appeared was 22% greater after training. The extent of ST-segment displacement at the same double product was less after training. These findings suggest that training, if sufficiently intense and prolonged, can result in a reduction in myocardial ischemia at the same or a higher double product.

Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neurodegeneration. They are also under intense investigation as delivery vectors for biotherapeutics. The ways in which EVs interact with recipient cells to influence cell physiology and deliver a macromolecular payload are at the early stages of exploration. A significant challenge within these studies is the ability to label EVs directly or indirectly with fluorescent probes to allow visualization without compromising functionality. Here, we present a thiol-based fluorescence labelling method allowing comprehensive analysis of the cellular uptake of prostate cancer derived EVs in live cells using confocal microscopy. Labelling of the EVs in this way did not influence their size and had no effect on their ability to induce differentiation of lung fibroblasts to myofibroblasts. For endocytosis analyses, depletion of key endocytic proteins and the use of chemical inhibitors (Dynasore, EIPA, Rottlerin and IPA-3) indicated that fluid-phase endocytosis and/or macropinocytosis was involved in EV internalisation. Over a period of six hours EVs were observed to increasingly co-localise with lysosomes, indicating a possible termination point following internalisation. Overall this method provides new opportunities for analysing the cellular dynamics of EVs as biological entities affecting cell and whole body physiology as well as investigating their potential as drug delivery vectors.

This study reports on the development of drug containing acrylic strips for delivering antimicrobial agents and compares the in vitro release pattern with dialysis tubing. Polyethylmethacrylic strips of suitable dimensions containing 10 to 50% chlorhexidine acetate, 40% metronidazole and 40% tetracycline were prepared. Daily release of the incorporated drugs into 1 ml aliquots was measured spectrophotometrically over a 14 day period. Similarly the release of chlorhexidine gluconate from various lengths of patent and heat sealed dialysis tubing was recorded for 4 days. At 30%, 40% and 50% admixtures the acrylic strips released chlorhexidine up to the 14 day period and a parallel bioassay confirmed the maintenance of antibacterial activity to this time. At the same admixture the release of metronidazole was greater than chlorhexidine and tetracycline. All drugs were released at high levels on day 1 followed by a marked fall in release by day 2 and progressive fall thereafter. The release from tubing was almost total within 24 hours and was independent of sealing the ends. The strips appear to have potential for prolonged drug delivery to periodontal pockets. Preliminary clinical use revealed no patient acceptability problems and alterations in subgingival flora were produced.

Colistin resistance has attracted substantial attention after colistin was considered as a last-resort drug for the treatment of infections caused by carbapenem-resistant and/or multidrug-resistant (MDR) Gram-negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has become an increasingly urgent issue worldwide. Despite many reviews, which summarized the prevalence, mechanisms, and structures of these genes in bacteria of human and animal origin, studies on the prevalence of mobile colistin resistance genes in aquaculture and their transmission between animals and humans remain scarce. Herein, we review recent reports on the prevalence of colistin resistance genes in animals, especially wildlife and aquaculture, and their possibility of transmission to humans via the food chain. This review also gives some insights into the routine surveillance, changing policy and replacement of polymyxins by polymyxin derivatives, molecular inhibitors, and traditional Chinese medicine to tackle colistin resistance.

BackgroundCarriage of carbapenem-resistant Enterobacteriaceae (CRE) in humans may contribute to the dissemination of CRE and impact on communities and healthcare facilities. Carbapenem-resistant Escherichia coli (CREC) is one of the major type of CRE in the human gut. Here, we describe a cross-sectional study to investigate the prevalence of CREC, and in particular the mcr-1 carrying CREC, in health volunteers in China.MethodsDuring September to December 2016, 3859 non-duplicated stool specimens were collected from healthy volunteers who received regular physical examinees in healthcare centers located in 19 provinces across China. Enrichment culture supplemented meropenem was used to isolate CREC. Carbapenemase producing determinants and the mcr-1 gene were determined by PCR amplification and sequencing. Isolates were further analyzed by antibiotic susceptibility test, genotyping, and whole genome analysis.FindingsA total of 92 non-duplicated CREC were isolated from 3859 stool specimens, among which 43 CREC are carbapenemase positive. In addition, the co-existence of blaNDM and mcr-1 was found in 14 CREC, which also showed resistance to the majority of all antimicrobial agents analyzed. The genetic background of these CREC isolates are highly diversified based on molecular typing. Furthermore, whole genome sequence indicated that NDM-5 is the predominant determinant conferring carbapenem resistance in CREC, and that NDM-5 carrying plasmids (IncX3) are very similar.InterpretationThe incidence of CREC carriage in healthy people in China was small; however, the co-existence of CREC with mcr-1 is disconcerting. Therefore, pre-screening prior to admission and monitoring of patients on high-dependency wards is highly recommended to control and prevent the dissemination of CRE in hospitals.Outstanding QuestionThe high prevalence of CREC in the healthy people should not be underestimated, as it may increase the risk of infection. This knowledge could have impact on the pre-screening and monitoring of CRE before patient administration.

The authors analyzed the holdings, circulations, and interlibrary loan (ILL) borrowing requests of the English-language monograph collection at the University of Colorado at Boulder. Data for each area were mapped to conspectus subject areas, using Library of Congress Classifications, and then compared. The resulting data and subject distributions were analyzed by overall holdings, transactions per item, percentage of collection circulated, and a ratio of ILL holdings to requests. The method of analysis used in this study could be fruitfully applied to other research collections to assist with remote storage, preservation, and collection development decisions.

Abstract A summary of the results of regional flood frequency analyses that have been carried out in many tropical and sub-tropical countries is presented. The results provide a set of flood estimation methods which should be of immediate usefulness in practical applications, bearing in mind the errors of generalization. By defining the representative values of the mean annual flood and of the flood frequency curves for each region, an attempt has been made to develop relationships between the methods and climatic characteristics. These show that adequate relationships can be obtained based solely on the median annual average rainfall and the median catchment area for the regions. In particular, the steepness of the regional flood frequency curve can be estimated reasonably well from these two parameters. The relationships confirm that, broadly speaking, for humid regions the “average” flood—the flood that occurs regularly every one or two years—is relatively large, but the flood frequency curve is not very steep; rare floods (occurring once in every 100 to 1000 years) are not very much larger than the average flood. Conversely, in arid regions, the average flood is small, but rare floods can be extremely large multiples of the average. These relationships provide a useful initial indication of the type of regional flood frequency estimation method likely to be found in tropical and sub-tropical regions throughout the world.

CONTEXT: Down syndrome (DS) is the most common genetic cause of mental retardation. However, the biological determinants of this are poorly understood. The serum sodium/myo-inositol cotransporter gene is located on chromosome 21, and myo-inositol affects neuronal survival and function. Nevertheless, few in vivo studies have examined the role of myo-inositol in DS. OBJECTIVE: To determine if people with DS have significant differences in brain myo-inositol concentration from controls and if, within people with DS, this is related to cognitive ability. DESIGN: A case-control study. SETTING: Outpatient. PARTICIPANTS: The sample was composed of 38 adults with DS without dementia (age range, 18-66 years) and 42 healthy controls (age range, 19-66 years). The DS and control groups did not differ significantly in age, sex, ethnic origin, apolipoprotein E status, or handedness. MAIN OUTCOME MEASURES: Hippocampal myo-inositol concentration and cognitive performance, as measured by the Cambridge Cognitive Examination. RESULTS: Hippocampal myo-inositol concentration was significantly higher in people with DS than in controls (P = .006), and within people with DS, increased myo-inositol concentration was significantly negatively correlated with overall cognitive ability (P = .04). CONCLUSIONS: Adults with DS have a significantly increased brain concentration of myo-inositol, and this is associated with reduced cognitive ability. Future studies are required to relate myo-inositol concentration in people with DS to brain development and increased risk for developing Alzheimer disease.

The incidence of this combined numerical defect of the dentition is assessed by a survey of 4598 orthodontic patients. The factors which may influence the reported incidence are considered. A subdivision into premaxillary, maxillary, mandibular and bimaxillary varieties is suggested on the grounds of the distribution of the teeth involved.

, little is known of the free nucleotides of mature seeds. The aims of the work described in this paper are to identify the major nucleotide components in mature pea seeds, to estimate their relative con- centrations and to examine the seeds for significant change in nucleotide pattern during storage. The metabolism of mature seeds is especially interesting in that they respire, albeit at a very low rate, over long periods of storage with little other detectable metabolic activity. EXPERIMENTAL

Abstract Abstract An annual water balance model of Lake Victoria is derived for the period 1925–2000. Regression techniques are used to derive annual inputs to the water balance, based on lake rainfall data, measured and derived inflows and estimated evaporation during the historical period. This approach acknowledges that runoff is a nonlinear function of lake rainfall. A longer inflow series is produced here which is representative of the whole inflow to the lake, rather than just from individual tributaries. The results show a good simulation of annual lake levels and outflows and capture the high lake level in 1997–1998. Climate change scenarios, from a recent global climate model experiment, are applied to the lake rainfall inflow series and evaporation data to estimate future water balances of the lake. The scenarios produce a potential fall in lake levels by the 2030s horizon, and a rise by the 2080s horizon. A discussion of the application of climate change data to this complex hydrological system is presented.

There is a sense in which, at the moment, group-analysts are in a position carparable to that of biologists in the early nineteenth century. Erasmus Darwin, I~r~arck, Buffon, Chambers- these mean were sure that evolution occurred, in spite of public ridicule and professional opposition, but they were unable to do much more than retain the notion of evolution as a private conviction, discussed among small groups of like-minded individuals. Their reticence was enforced by the need to find an adequate causal mechanism. They were sure evolution occurred, but they could-ot see how; and if one is going to be taken seriously by fellow-professionals, let alone the general public, they-and we- know that one must base one’s convictions on more than an act of faith. As group-analysts, we know that groups ’work ’- that is to say we are confident that the majority of people who enter a group-analytic group at the very least express themselves better off for having had the experience. However, we are to some extent still in the dark about just why that should be so; about the fundamental nature of the mechanisms enabling change and growth in the analytic

A tension pneumothorax is a life threatening condition in which there is a large rise in intrathoracic pressure on the side of the affected hemithorax. This condition may rapidly lead to death. Prompt treatment of the condition is required and most of the texts on the treatment of patients with this condition suggest that the pressure is released by the placement of a large bore trocar and cannula through the second intercostal space at the mid-clavicular line on the affected side.1 This procedure is intended to be diagnostic and temporarily therapeutic, relieving the pressure enough to “buy time” while preparations are made for placement of a chest drain. We report three cases of tension pneumothorax that were not responsive to needle decompression. We believe that these cases illustrate a potential problem with needle decompression that may lead the less experienced practitioner to doubt their diagnosis with possible dire consequences for the patient. An 18 year old man was admitted to the emergency department after crashing his car into a shop window. He had been trapped at scene by the displaced steering wheel, which was pressing against his chest. On arrival in the department he was complaining of severe left sided chest pain and difficulty in breathing. The patient was in severe respiratory distress and further examination revealed a resonant left hemithorax with absent breath sounds. A diagnosis of a left sided tension pneumothorax was made and a 14 gauge cannula …

H.E. Hurst spent some 60 years studying the Nile for the Egyptian government, and laid the foundation for a monumental set of hydrological records and investigations. His studies of the size of over-year reservoirs needed to maintain a given yield from Nile flows showed that this was greater than that based on random series. This finding, known as the Hurst phenomenon, was confirmed by other natural series and led to important advances in practical and theoretical statistics. His work led to the design of the Aswan High Dam and to continued research in Egypt.Editor D. Koutsoyiannis; Guest editor E. Eris

(1981). A commemorative essay on W.R. Bion's theory of thinking. Journal of Child Psychotherapy: Vol. 7, No. 2, pp. 181-192.

BACKGROUND: More older people are living in the community with multiple diagnoses and medications. Managing multiple medications produces issues of unrivalled complexity for those involved. Despite increasing literature on the subject, gaps remain in understanding how, why and for whom complex medication management works, and therefore how best to improve practice and outcomes. MEMORABLE, MEdication Management in Older people: Realist Approaches Based on Literature and Evaluation, aimed to address these gaps. METHODS: MEMORABLE used realism to understand causal paths within medication management. Informed by RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines, MEMORABLE involved three overlapping work packages: 1) Realist Review of the literature (24 articles on medication management exploring causality); 2) Realist Evaluation (50 realist-informed interviews with older people, family carers and health and care practitioners, explaining their experiences); and 3) data synthesis and theorising from 1) and 2). RESULTS: Medication management was viewed from the perspective of 'implementation' and structured into five stages: identifying a problem (Stage 1), getting a diagnosis and/or medications (Stage 2), starting, changing or stopping medications (Stage 3), continuing to take medications (Stage 4), and reviewing/reconciling medications (Stage 5). Three individual stages (1, 3 and 4) are conducted by the older person sometimes with family carer support when they balance routines, coping and risk. Stages 2 and 5 are interpersonal where the older person works with a practitioner-prescriber-reviewer, perhaps with carer involvement. Applying Normalisation Process Theory, four steps were identified within each stage: 1) sense making: information, clarification; 2) action: shared-decision-making; 3) reflection/monitoring; and 4) enduring relationships, based on collaboration and mutual trust. In a detailed analysis of Stage 5: Reviewing/reconciling medications, adopting the lens of 'burden', MEMORABLE identified five burdens amenable to mitigation: ambiguity, concealment, unfamiliarity, fragmentation and exclusion. Two initial improvement propositions were identified for further research: a risk screening tool and individualised information. CONCLUSIONS: Older people and family carers often find medication management challenging and burdensome particularly for complex regimens. Practitioners need to be aware of this potential challenge, and work with older people and their carers to minimise the burden associated with medication management. TRIAL REGISTRATION: PROSPERO 2016:CRD42016043506.

RATIONALE: Patients without a known history of lung disease presenting with a spontaneous pneumothorax are generally diagnosed as having primary spontaneous pneumothorax. However, occult diffuse cystic lung diseases such as Birt-Hogg-Dubé syndrome (BHD), lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH) can also first present with a spontaneous pneumothorax, and their early identification by high-resolution computed tomographic (HRCT) chest imaging has implications for subsequent management. OBJECTIVES: The objective of our study was to evaluate the cost-effectiveness of HRCT chest imaging to facilitate early diagnosis of LAM, BHD, and PLCH. METHODS: We constructed a Markov state-transition model to assess the cost-effectiveness of screening HRCT to facilitate early diagnosis of diffuse cystic lung diseases in patients presenting with an apparent primary spontaneous pneumothorax. Baseline data for prevalence of BHD, LAM, and PLCH and rates of recurrent pneumothoraces in each of these diseases were derived from the literature. Costs were extracted from 2014 Medicare data. We compared a strategy of HRCT screening followed by pleurodesis in patients with LAM, BHD, or PLCH versus conventional management with no HRCT screening. MEASUREMENTS AND MAIN RESULTS: In our base case analysis, screening for the presence of BHD, LAM, or PLCH in patients presenting with a spontaneous pneumothorax was cost effective, with a marginal cost-effectiveness ratio of $1,427 per quality-adjusted life-year gained. Sensitivity analysis showed that screening HRCT remained cost effective for diffuse cystic lung diseases prevalence as low as 0.01%. CONCLUSIONS: HRCT image screening for BHD, LAM, and PLCH in patients with apparent primary spontaneous pneumothorax is cost effective. Clinicians should consider performing a screening HRCT in patients presenting with apparent primary spontaneous pneumothorax.

<h3>Objective</h3> To examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW). <h3>Methods</h3> The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016. <h3>Results</h3> The 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (<i>p</i> = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04–19.01). There were no significant differences for fetal loss (2.8% vs 0%, <i>p</i> = 0.126) or MCMs (5.2% vs 1.9%, <i>p</i> = 0.185; OR 2.86, 95% CI 0.65–12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (<i>p</i> = 0.046). <h3>Conclusions</h3> The findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.