Studies in the population dynamics of some Teesdale plants

The study was essentially a demographic one. Few studies of this kind have been carried out on rare plant populations. Permanent quadrats (selected subjectively for the presence of some Teesdale plants, including Gentlana verna and Polygala amarelle) were established on Widdybank and Cronkley Fells in the Northern Pennines. The quadrats were all established on the grazed or eroding areas of sugar limestone grassland. For each quadrat the grid positions of all the individuals of the species being recorded were plotted on a chart. The fate of the initially recorded mixed-age population and that of all subsequent additions was noted at each visit. Larger permanently marked sample sites, usually adjacent to a permanent quadrat, were recorded once a year for the number of flowering and non-flowering individuals. Individuals which flowered were then recorded for the number of flowers, fruits and seeds they produced. From these data the population flux, mortality, survival and age-distribution of the individuals in the quadrats were obtained. The relative importance of sexual reproduction was ascertained by closely following the appearance of seedlings and vegetative shoots in each of the quadrats where a species produced both

TLR-mediated activation of Waldenström macroglobulinemia B cells reveals an uncoupling from plasma cell differentiation

Waldenstr¨om macroglobulinemia (WM) is a rare malignancy in which clonal B cells infiltrate the bone marrow and give rise to a smaller compartment of neoplastic plasma cells that secrete monoclonal immunoglobulin M paraprotein. Recent studies into underlying mutations in WM have enabled a much greater insight into the pathogenesis of this lymphoma. However, there is considerably less characterization of the way in which WM B cells differentiate and how they respond to immune stimuli. In this study, we assess WM B-cell differentiation using an established in vitro model system. Using T-cell–dependent conditions, we obtained CD1381 plasma cells from WM samples with a frequency similar to experiments performed with B cells from normal donors. Unexpectedly, a proportion of the WM B cells failed to upregulate CD38, a surface marker that is normally associated with plasmablast transition and maintained as the cells proceed with differentiation. In normal B cells, concomitant Toll-like receptor 7 (TLR7) activation and B-cell receptor cross-linking drives proliferation, followed by differentiation at similar efficiency to CD40-mediated stimulation. In contrast, we found that, upon stimulation with TLR7 agonist R848, WM B cells failed to execute the appropriate changes in transcriptional regulators, identifying an uncoupling of TLR signaling from the plasma cell differentiation program. Provision of CD40L was sufficient to overcome this defect. Thus, the limited clonotypic WM plasma cell differentiation observed in vivo may result from a strict requirement for integrated activation

Are agri‐environment schemes successful in delivering conservation grazing management on saltmarsh?

1.Grasslands occur around the globe and, in temperate regions, their natural management by fire, drought and wild herbivores has largely been replaced by grazing with domestic livestock. Successful management for agriculture is not always suitable for conservation and can have a detrimental effect on biodiversity. Conservation grazing of saltmarshes, delivered through agri‐environment schemes, may provide a solution to counteract biodiversity loss by providing farmers with financial incentives to graze these internationally important coastal wetlands more sensitively. 2.To assess whether conservation grazing is being achieved, and whether agri‐environment schemes are effective in delivering this management, we conducted a national survey on English saltmarshes, scoring the management on each site as optimal, suboptimal or detrimental in terms of suitability for achieving conservation aims for five aspects of grazing: presence, stock type, intensity, timing and habitat impact. 3.Although most saltmarshes suitable for grazing in England were grazed, conservation grazing was not being achieved. Sites under agri‐environment management for longer did score higher and approached optimal levels in terms of grazing intensity in one region, but sites with agri‐environment agreements were no more likely to be grazed at optimal conservation levels than sites without them overall, indicating that agri‐environment schemes, in their current form, are an ineffective delivery mechanism for conservation grazing on saltmarsh. 4.The low specificity of agri‐environment prescription wording may contribute to this failure, with prescriptions either being vague or specifying suboptimal or detrimental management objectives, particularly for grazing intensity, timing and stock type. These objectives are often set too high or too low, during unsuitable periods, or using stock types inappropriate for achieving conservation aims. 5.Synthesis and applications. Our national survey indicates that agri‐environment schemes are not currently delivering conservation grazing on English saltmarshes. Agri‐environment schemes are the only mechanism through which such grazing can be implemented on a national scale, so improving their effectiveness is a priority. Policymakers, researchers and managers need to work together to ensure better translation of conservation guidelines into schemes, increasing the specificity of management prescriptions and improving understanding of the need for management measures. A more detailed and reliable system of auditing to ensure that management activities are taking place would be beneficial, or alternatively moving to a results‐based scheme where payments are made on desirable outcomes rather than on evidence of management

The Making of a Self-Neglect Severity Scale

Research in elder self-neglect has lagged behind that of other forms of mistreatment, despite the fact that self-neglect is the most common allegation reported to Adult Protective Service agencies throughout the US. The lack of a gold-standard to measure self-neglect has hampered efforts to study this phenomenon. Researchers designed the Self-neglect Severity Scale (SSS) based on interviews with Adult Protective Service workers and a national expert panel. The SSS is based on observation and interview and is administered in the home to include an environmental assessment. It was piloted, extensively field tested and then revised. The CREST SSS was developed using survey data and consultation with experts in the field. This instrument utilizes observer ratings, interview responses, and assesses subjects physical and environmental domains. It also assesses functional status as it relates to health and safety issues. After field and pilot testing the SSS was finalized and is currently undergoing reliability and validity testing. The CREST SSS was developed as a state scale to provide a common language for describing cases of self-neglect. It is the first self-neglect severity scale available to researchers. If found to be both reliable and valid it can be used in future intervention studies

TGFβ activation primes canonical Wnt signaling through the downregulation of AXIN2

OBJECTIVES: Aberrant activation of Wnt signaling has been observed in systemic sclerosis (SSc) affected tissues. This study aimed to determine the role of transforming growth factor (TGF)β in driving the increased Wnt signaling, through modulation of AXIN2, a critical regulator of Wnt canonical pathway. METHODS: Canonical Wnt signaling activation was analyzed by TOPFlash TCF/LEF promoter assays. AXIN2 was evaluated in vitro by analysis of AXIN2 primary/mature transcripts expression and decay, TβRI blockade, siRNA-mediated TTP-1 depletion and through XAV-939-mediated AXIN2 stabilisation. In vivo, Axin2 mRNA and protein expression was determined in skin and lung biopsies from TβRIIΔk-fib transgenic mice and littermate controls. RESULTS: SSc fibroblasts display increased response to canonical Wnt ligands despite basal levels of Wnt signaling comparable to healthy control (HC) fibroblasts in vitro. Notably, we show that SSc fibroblasts express reduced basal expression of AXIN2, which is caused by endogenous TGFβ-dependent increase of AXIN2 mRNA decay. Accordingly, we observed that TGFβ decreased AXIN2 expression both in vitro in HC fibroblasts and in vivo, employing TβRIIΔk-fib transgenic mice. Additionally, we demonstrate by AXIN2 loss and gain of function experiments, that the TGFβ-induced increased response to Wnt activation characteristic of SSc fibroblasts is dependent on reduced AXIN2 bioavailability. CONCLUSIONS: This study highlights the importance of reduced AXIN2 bioavailability in mediating the increased canonical Wnt response observed in SSc fibroblasts. This novel mechanism extends our understanding of the processes involved in Wnt/β-catenin-driven pathology and supports the rationale for targeting the TGFβ pathway to regulate the aberrant Wnt signaling observed during fibrosis. This article is protected by copyright. All rights reserved

Diagnostic change 10 years after a first episode of psychosis

Background. A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diag-noses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an inci-dence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change. Method. Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables asso-ciated with change were examined using logistic regression and likelihood ratio tests. Results. Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years

Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies

<p>Abstract</p> <p>Background</p> <p>Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained.</p> <p>Methods</p> <p>To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a $2.00 bill or no incentive with the blood spot collection kits.</p> <p>Results</p> <p>The average time between the venipuncture sample refusal and recruitment for the blood spot collection was 4.4 years. Thirty-seven percent of cases and 28$2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables.</p> <p>Conclusion</p> <p>This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies.</p

Biological and psychosocial risk factors for psychotic major depression

AIMS: Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders. METHODS: Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs. RESULTS: Living alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD. CONCLUSIONS: Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.status: publishe