Photobacterium profundum under Pressure:A MS-Based Label-Free Quantitative Proteomics Study

Photobacterium profundum SS9 is a Gram-negative bacterium, originally collected from the Sulu Sea. Its genome consists of two chromosomes and a 80 kb plasmid. Although it can grow under a wide range of pressures, P. profundum grows optimally at 28 MPa and 15°C. Its ability to grow at atmospheric pressure allows for both easy genetic manipulation and culture, making it a model organism to study piezophily. Here, we report a shotgun proteomic analysis of P. profundum grown at atmospheric compared to high pressure using label-free quantitation and mass spectrometry analysis. We have identified differentially expressed proteins involved in high pressure adaptation, which have been previously reported using other methods. Proteins involved in key metabolic pathways were also identified as being differentially expressed. Proteins involved in the glycolysis/gluconeogenesis pathway were up-regulated at high pressure. Conversely, several proteins involved in the oxidative phosphorylation pathway were up-regulated at atmospheric pressure. Some of the proteins that were differentially identified are regulated directly in response to the physical impact of pressure. The expression of some proteins involved in nutrient transport or assimilation, are likely to be directly regulated by pressure. In a natural environment, different hydrostatic pressures represent distinct ecosystems with their own particular nutrient limitations and abundances. However, the only variable considered in this study was atmospheric pressure

Women's secure hospital care pathways in practice: a qualitative analysis of clinicians views in England and Wales

BACKGROUND: In England and Wales women form a small but significant group within the wider, largely male, secure hospital population. Secure hospitals are designed to assess and treat individuals with both mental health problems and significant criminal behaviour. The theoretical approach to the care of secure hospital women is increasingly informed by a grasp of gender-specific issues. However, there is a lack of evidence on the adequacy of current structures and processes of care delivery. METHODS: This qualitative study explores the nature and quality of care pathways for women in low and medium secure hospital beds by eliciting participants' views of factors enhancing or impeding care. Beds are publicly funded and provided either by the National Health Service (NHS) or the Independent Sector (IS). Participants from both sectors were local experts (40 Consultant Psychiatrists, 7 Service Managers) who were well placed to describe their immediate health environment. RESULTS: Evidence from the study indicates that participants were focused on the physical relocation of women to less secure conditions, even though many women do not readily achieve this.Participants were alert to potential conflicts between ideal care and affordable care. Ideal care was compromised by the absence of suitable local services (beds or community placements), curtailed episodes of care and changes of care team. It was promoted by an awareness of the specific needs of women, continuity of care and support for teams unfamiliar with women's needs. CONCLUSION: Future service design must address these challenges in care delivery, incorporating a better understanding of and response to the ways the system can echo women's experiences of trauma and their negative attachment histories. Specifically, critical transitions in care must not be allowed to further reinforce the discontinuity, failure and rejection experienced by individual women earlier in their lives

Environmental Adaptation: Genomic Analysis of the Piezotolerant and Psychrotolerant Deep-Sea Iron Reducing Bacterium Shewanella piezotolerans WP3

Shewanella species are widespread in various environments. Here, the genome sequence of Shewanella piezotolerans WP3, a piezotolerant and psychrotolerant iron reducing bacterium from deep-sea sediment was determined with related functional analysis to study its environmental adaptation mechanisms. The genome of WP3 consists of 5,396,476 base pairs (bp) with 4,944 open reading frames (ORFs). It possesses numerous genes or gene clusters which help it to cope with extreme living conditions such as genes for two sets of flagellum systems, structural RNA modification, eicosapentaenoic acid (EPA) biosynthesis and osmolyte transport and synthesis. And WP3 contains 55 open reading frames encoding putative c-type cytochromes which are substantial to its wide environmental adaptation ability. The mtr-omc gene cluster involved in the insoluble metal reduction in the Shewanella genus was identified and compared. The two sets of flagellum systems were found to be differentially regulated under low temperature and high pressure; the lateral flagellum system was found essential for its motility and living at low temperature

Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma

This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ⩾12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ⩾12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ⩾12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23–0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ⩾12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings

Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs

Chantier qualité GAInternational audienceABSTRACT: BACKGROUND: This study aimed to measure the gait abnormalities in GRMD (Golden retriever muscular dystrophy) dogs during growth and disease progression using an ambulatory gait analyzer (3D-accelerometers) as a possible tool to assess the effects of a therapeutic intervention. METHODS: Six healthy and twelve GRMD dogs were evaluated twice monthly, from the age of two to nine months. The evolution of each gait variable previously shown to be modified in control and dystrophin-deficient adults was assessed using two-ways variance analysis (age, clinical status) with repeated measurements. A principal component analysis (PCA) was applied to perfect multivariate data interpretation. RESULTS: Speed, stride length, total power and force significantly already decreased (p < 0.01) at the age of 2 months. The other gait variables (stride frequency, relative power distributions along the three axes) became modified at later stages. Using the PCA analysis, a global gait index taking into account the main gait variables was calculated, and was also consistent to detect the early changes in the GRMD gait patterns, as well as the progressive degradation of gait quality. CONCLUSION: The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials

The rise of dentine hypersensitivity and tooth wear in an ageing population

Our understanding of the aetiology of dentine hypersensitivity (DH) has changed dramatically over the past few decades. It is no longer an enigma, but other problems exist. The prevalence of DH in the world and in particular in the UK is increasing, predominately due to increases in tooth wear and the erosive dietary intake in the younger population. DH is increasingly reported in all age groups and is shown to provide clinical indication of an active erosive tooth wear. As the population ages and possibly retain teeth for longer, the likelihood of tooth wear and DH could increase. This paper describes the prevalence, aetiology, diagnosis and management of DH in relation to tooth wear, which work together through a surface phenomenon. The aim is to raise awareness of the conditions and to help inform a prevention strategy in an ageing population, which starts from younger age groups to reduce disease into older age

On the Bounds of Function Approximations

Within machine learning, the subfield of Neural Architecture Search (NAS) has recently garnered research attention due to its ability to improve upon human-designed models. However, the computational requirements for finding an exact solution to this problem are often intractable, and the design of the search space still requires manual intervention. In this paper we attempt to establish a formalized framework from which we can better understand the computational bounds of NAS in relation to its search space. For this, we first reformulate the function approximation problem in terms of sequences of functions, and we call it the Function Approximation (FA) problem; then we show that it is computationally infeasible to devise a procedure that solves FA for all functions to zero error, regardless of the search space. We show also that such error will be minimal if a specific class of functions is present in the search space. Subsequently, we show that machine learning as a mathematical problem is a solution strategy for FA, albeit not an effective one, and further describe a stronger version of this approach: the Approximate Architectural Search Problem (a-ASP), which is the mathematical equivalent of NAS. We leverage the framework from this paper and results from the literature to describe the conditions under which a-ASP can potentially solve FA as well as an exhaustive search, but in polynomial time.Comment: Accepted as a full paper at ICANN 2019. The final, authenticated publication will be available at https://doi.org/10.1007/978-3-030-30487-4_3

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Configuring Balanced Scorecards for Measuring Health System Performance: Evidence from 5 Years' Evaluation in Afghanistan

Anbrasi Edward and colleagues report the results of a balanced scorecard performance system used to examine 29 key performance indicators over a 5-year period in Afghanistan, between 2004 and 2008