Modelling Cognitive Decline in the Hypertension in the Very Elderly Trial [HYVET] and Proposed Risk Tables for Population Use

Although, on average, cognition declines with age, cognition in older adults is a dynamic process. Hypertension is associated with greater decline in cognition with age, but whether treatment of hypertension affects this is uncertain. Here, we modelled dynamics of cognition in relation to the treatment of hypertension, to see if treatment effects might better be discerned by a model that included baseline measures of cognition and consequent mortalityThis is a secondary analysis of the Hypertension in the Very Elderly Trial (HYVET), a double blind, placebo controlled trial of indapamide, with or without perindopril, in people aged 80+ years at enrollment. Cognitive states were defined in relation to errors on the Mini-Mental State Examination, with more errors signifying worse cognition. Change in cognitive state was evaluated using a dynamic model of cognitive transition. In the model, the probabilities of transitions between cognitive states is represented by a Poisson distribution, with the Poisson mean dependent on the baseline cognitive state. The dynamic model of cognitive transition was good (R(2) = 0.74) both for those on placebo and (0.86) for those on active treatment. The probability of maintaining cognitive function, based on baseline function, was slightly higher in the actively treated group (e.g., for those with the fewest baseline errors, the chance of staying in that state was 63% for those on treatment, compared with 60% for those on placebo). Outcomes at two and four years could be predicted based on the initial state and treatment.A dynamic model of cognition that allows all outcomes (cognitive worsening, stability improvement or death) to be categorized simultaneously detected small but consistent differences between treatment and control groups (in favour of treatment) amongst very elderly people treated for hypertension. The model showed good fit, and suggests that most change in cognition in very elderly people is small, and depends on their baseline state and on treatment. Additional work is needed to understand whether this modelling approach is well suited to the valuation of small effects, especially in the face of mortality differences between treatment groups.ClinicalTrials.gov NCT0012281

Off-axis cavity-enhanced absorption spectroscopy of 14NH3 in air using a gain-switched frequency comb at 1.514 μm

A custom-designed gain-switched frequency comb (GSFC) source was passively coupled to a medium finesse (F ≈ 522) cavity in off-axis configuration for the detection of ammonia (14NH3) in static dry air. The absorption of ammonia was detected in the near infrared spectral region between 6604 and 6607 cm−1 using a Fourier transform detection scheme. More than 30 lines of the GSFC output (free spectral range 2.5 GHz) overlapped with the strongest ro-vibrational ammonia absorption features in that spectral region. With the cavity in off-axis configuration, an NH3 detection limit of ∼3.7 ppmv in 20 s was accomplished in a laboratory environment. The experimental performance of the prototype spectrometer was characterized; advantages, drawbacks and the potential for future applications are discusse

Social contact as a strategy to reduce stigma in low- and middle-income countries: A systematic review and expert perspectives

Social contact (SC) has been identified as a promising strategy for stigma reduction. Different types of SC exist. Various scholars defined positive factors to strengthen SC. This study aims to investigate the application and effectiveness of SC as a strategy to reduce stigmatisation across stigmas, settings and populations in low- and middle-income countries (LMICs). We specifically examine the use of positive factors. A systematic review was conducted in twelve electronic databases using key terms related to stigma AND social contact AND intervention AND LMICs. Data were synthesised narratively. Study quality was assessed with the Joanna Briggs Institute critical appraisal checklists. Additionally, semi-structured interviews were used with first/corresponding authors of included publications to investigate their practical experiences with SC. Forty-four studies (55 publications) were identified. Various stigmas (n = 16) were targeted, including mental health (43%). Indirect (n = 18) and direct contact (n = 16) were used most frequently, followed by collaboration, imagined and vicarious contact, or a combination. The most applied additional strategy was education. Almost half of the studies, explicitly or implicitly, described positive factors for SC, such as PWLE training or disconfirming stereotypes. The majority suggested that SC is effective in reducing stigma, although inconsistent reporting overshadows conclusions. Perspectives of people with lived experience (PWLE) were infrequently included. Expert perspectives stressed the importance of contextualisation, PWLE participation, and evaluation of SC. This study provides an overview of SC as a stigma reduction strategy within LMICs. Conclusions about which type of SC is more effective or whether SC is more effective for a specific stigma category cannot be drawn. We recommend future research to strengthen reporting on effectiveness as well as PWLE perspective and SC processes, and to further critically examine the potential of SC. An overview of positive factors applied to strengthen SC is provided, which can stimulate reflection and guide future SC

Haemoglobin, anaemia, dementia and cognitive decline in the elderly, a systematic review

<p>Abstract</p> <p>Background</p> <p>Anaemia may increase risk of dementia or cognitive decline. There is also evidence that high haemoglobin levels increase risk of stroke, and consequently possible cognitive impairment. The elderly are more at risk of developing dementia and are also more likely to suffer from anaemia, although there is relatively little longitudinal literature addressing this association.</p> <p>Methods</p> <p>To evaluate the evidence for any relationship between incident cognitive decline or dementia in the elderly and anaemia or haemoglobin level, we conducted a systematic review and meta-analyses of peer reviewed publications. Medline, Embase and PsychInfo were searched for English language publications between 1996 and 2006. Criteria for inclusion were longitudinal studies of subjects aged ≥65, with primary outcomes of incident dementia or cognitive decline. Other designs were excluded.</p> <p>Results</p> <p>Three papers were identified and only two were able to be combined into a meta-analysis. The pooled hazard ratio for these two studies was 1.94 (95 percent confidence intervals of 1.32–2.87) showing a significantly increased risk of incident dementia with anaemia. It was not possible to investigate the effect of higher levels of haemoglobin.</p> <p>Conclusion</p> <p>Anaemia is one factor to bear in mind when evaluating risk of incident dementia. However, there are few data available and the studies were methodologically varied so a cautionary note needs to be sounded and our primary recommendation is that further robust research be carried out.</p

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study.

BACKGROUND: Schistosomiasis remains a global public health challenge, with 93% of the ~237 million infections occurring in sub-Saharan Africa. Though rarely fatal, its recurring nature makes it a lifetime disorder with significant chronic health burdens. Much of its negative health impact is due to non-specific conditions such as anemia, undernutrition, pain, exercise intolerance, poor school performance, and decreased work capacity. This makes it difficult to estimate the disease burden specific to schistosomiasis using the standard DALY metric. METHODOLOGY/PRINCIPAL FINDINGS: In our study, we used Pediatric Quality of Life Inventory (PedsQL), a modular instrument available for ages 2-18 years, to assess health-related quality of life (HrQoL) among children living in a Schistosoma haematobium-endemic area in coastal Kenya. The PedsQL questionnaires were administered by interview to children aged 5-18 years (and their parents) in five villages spread across three districts. HrQoL (total score) was significantly lower in villages with high prevalence of S. haematobium (-4.0%, p<0.001) and among the lower socioeconomic quartiles (-2.0%, p<0.05). A greater effect was seen in the psychosocial scales as compared to the physical function scale. In moderate prevalence villages, detection of any parasite eggs in the urine was associated with a significant 2.1% (p<0.05) reduction in total score. The PedsQL reliabilities were generally high (Cronbach alphas ≥0.70), floor effects were acceptable, and identification of children from low socioeconomic standing was valid. CONCLUSIONS/SIGNIFICANCE: We conclude that exposure to urogenital schistosomiasis is associated with a 2-4% reduction in HrQoL. Further research is warranted to determine the reproducibility and responsiveness properties of QoL testing in relation to schistosomiasis. We anticipate that a case definition based on more sensitive parasitological diagnosis among younger children will better define the immediate and long-term HrQoL impact of Schistosoma infection

Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan

CD4 positive T helper cells control many aspects of specific immunity. These cells are specific for peptides derived from protein antigens and presented by molecules of the extremely polymorphic major histocompatibility complex (MHC) class II system. The identification of peptides that bind to MHC class II molecules is therefore of pivotal importance for rational discovery of immune epitopes. HLA-DR is a prominent example of a human MHC class II. Here, we present a method, NetMHCIIpan, that allows for pan-specific predictions of peptide binding to any HLA-DR molecule of known sequence. The method is derived from a large compilation of quantitative HLA-DR binding events covering 14 of the more than 500 known HLA-DR alleles. Taking both peptide and HLA sequence information into account, the method can generalize and predict peptide binding also for HLA-DR molecules where experimental data is absent. Validation of the method includes identification of endogenously derived HLA class II ligands, cross-validation, leave-one-molecule-out, and binding motif identification for hitherto uncharacterized HLA-DR molecules. The validation shows that the method can successfully predict binding for HLA-DR molecules-even in the absence of specific data for the particular molecule in question. Moreover, when compared to TEPITOPE, currently the only other publicly available prediction method aiming at providing broad HLA-DR allelic coverage, NetMHCIIpan performs equivalently for alleles included in the training of TEPITOPE while outperforming TEPITOPE on novel alleles. We propose that the method can be used to identify those hitherto uncharacterized alleles, which should be addressed experimentally in future updates of the method to cover the polymorphism of HLA-DR most efficiently. We thus conclude that the presented method meets the challenge of keeping up with the MHC polymorphism discovery rate and that it can be used to sample the MHC "space," enabling a highly efficient iterative process for improving MHC class II binding predictions

Integrated dual optical frequency comb source

A monolithically integrated dual-channel optical frequency comb source is demonstrated in this paper. Three lasers are integrated on a single chip using a regrowth-free fabrication process in a master-slave-slave configuration. The master laser’s power is split equally using a 1x2 multimode interference coupler and injection locks the two slave lasers. The slave lasers are gain-switched to produce dual optical frequency combs at 4.1 GHz and 5 GHz. To the best of our knowledge, this is the first demonstration of a dual optical frequency comb source with all light sources monolithically integrated in a photonic integrated circuit (PIC)

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

Since HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to Minimal Hepatic Encephalopathy (MHE) in the absence of cirrhosis