Comparative performance of bone char-based filters for the removal of fluoride from drinking water

There is a great need for effective, reliable and inexpensive filters for the removal of fluoride for the millions of people affected in low and middle-income countries. This paper compares field and laboratory performance of bone char (BC) filters and filters, known as contact precipitation (CP), based on a combination of bone char and calcium-phosphate pellets

Use of a tablet-based system to perform abdominal ultrasounds in a field investigation of schistosomiasis-related morbidity in western Kenya

Chronic intestinal schistosomiasis can cause severe hepatosplenic disease and is a neglected tropical disease of public health importance in sub-Saharan Africa, including Kenya. Although the goal of control programs is to reduce morbidity, milestones for program performance focus on reductions in prevalence and intensity of infection, rather than actual measures of morbidity. Using ultrasound to measure hepatosplenic disease severity is an accepted method of determining schistosomiasis-related morbidity; however, ultrasound has not historically been considered a field-deployable tool because of equipment limitations and unavailability of expertise. A point-of-care tablet-based ultrasound system was used to perform abdominal ultrasounds in a field investigation of schistosomiasis-related morbidity in western Kenya; during the study, other pathologies and pregnancies were also identified via ultrasound, and participants referred to care. Recent technological advances may make it more feasible to implement ultrasound as part of a control program and can also offer important benefits to the community

The development of bone char-based filters for the removal of flouride from drinking water

Millions of people rely on drinking water that contains excess fluoride. Only few fluoride removal techniques have been implemented on a wider scale in low and middle income countries. One of these methods, bone char filtration, is highly efficient. However, its lifespan is rather limited. This paper presents first laboratory results and field testing of a new fluoride removal technology, based on a combination of bone char and calcium-phosphate pellets. These chemicals are slowly released to the water for fluoride precipitation. Although this method, commonly referred to as contact precipitation is known, the development of such pellets is new. Fixed-bed laboratory experiments show that this mixture of materials can increase filter uptake capacity by a factor of 3 and more. However, to reduce the phosphate concentration in the treated water, the design of full-scale community filters for field testing has to be slightly modified

DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance

Background: Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients. Methods: We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint. Results: The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027). Conclusions: DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol

Scaling Up the 2010 World Health Organization HIV Treatment Guidelines in Resource-Limited Settings: A Model-Based Analysis

Rochelle Walensky and colleagues use a model-based analysis to examine which of the 2010 WHO antiretroviral therapy guidelines should be implemented first in resource-limited settings by ranking them according to survival, cost-effectiveness, and equity

Delivery Practices and Associated Factors among Mothers Seeking Child Welfare Services in Selected Health Facilities in Nyandarua South District, Kenya

<p>Abstract</p> <p>Background</p> <p>A measure of the proportion of deliveries assisted by skilled attendants is one of the indicators of progress towards achieving Millennium Development Goal (MDG) 5, which aims at improving maternal health. This study aimed at establishing delivery practices and associated factors among mothers seeking child welfare services at selected health facilities in Nyandarua South district, Kenya to determine whether mothers were receiving appropriate delivery care.</p> <p>Methods</p> <p>A hospital-based cross-sectional survey among women who had recently delivered while in the study area was carried out between August and October 2009. Binary Logistic regression was used to identify factors that predicted mothers' delivery practice.</p> <p>Results</p> <p>Among the 409 mothers who participated in the study, 1170 deliveries were reported. Of all the deliveries reported, 51.8% were attended by unskilled birth attendants. Among the deliveries attended by unskilled birth attendants, 38.6% (452/1170) were by neighbors and/or relatives. Traditional Birth Attendants attended 1.5% (17/1170) of the deliveries while in 11.7% (137/1170) of the deliveries were self administered. Mothers who had unskilled birth attendance were more likely to have <3 years of education (Adjusted Odds ratio [AOR] 19.2, 95% confidence interval [CI] 1.7 - 212.8) and with more than three deliveries in a life time (AOR 3.8, 95% CI 2.3 - 6.4). Mothers with perceived similarity in delivery attendance among skilled and unskilled delivery attendants were associated with unsafe delivery practice (AOR 1.9, 95% CI 1.1 - 3.4). Mother's with lower knowledge score on safe delivery (%) were more likely to have unskilled delivery attendance (AOR 36.5, 95% CI 4.3 - 309.3).</p> <p>Conclusion</p> <p>Among the mothers interviewed, utilization of skilled delivery attendance services was still low with a high number of deliveries being attended by unqualified lay persons. There is need to implement cost effective and sustainable measures to improve the quality of maternal health services with an aim of promoting safe delivery and hence reducing maternal mortality.</p

Activation of Hypoxia Inducible Factor 1 Is a General Phenomenon in Infections with Human Pathogens

Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections

Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II–III colorectal cancer from the SCOT and QUASAR 2 trials: A retrospective analysis

Background Tumour-infiltrating CD8+ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. Methods We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8+, CD20+, FoxP3+, and CD68+ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II–III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. Findings After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8IE) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75vs25] 0·73 [95% CI 0·68–0·79], p=2·5 × 10−16), and of intrastromal FoxP3 (FoxP3IS; 0·71 [0·64–0·78], p=1·5 × 10−13) but not as strongly in the epithelium (FoxP3IE; 0·89 [0·84–0·96], p=1·5 × 10−4). Associations of other markers with recurrence-free interval were moderate. CD8IE and FoxP3IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8IE-FoxP3IS) was superior when assessed as a continuous variable (adjusted [a]HR75 vs 25 0·70 [95% CI 0·63–0·78], p=5·1 × 10−11) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29–2·20], p=1·3 × 10−4; low vs high 2·58 [1·91–3·49], p=7·9 × 10−10), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8IE-FoxP3IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR75 vs 25 0·84 [95% CI 0·73–0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17–2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89–1·88], p=0·17). Interpretation Combined evaluation of CD8IE and FoxP3IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3IS cells as an immunotherapy target in colorectal cancer might be merited

Tumour-infiltrating CD8+ lymphocytes and colorectal cancer recurrence by tumour and nodal stage

Background Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage II/III colorectal cancer (CRC). We aimed to determine whether this association varies across this heterogeneous group. Methods We performed a pooled analysis of 1804 CRCs from the QUASAR2 and VICTOR trials. Intratumoural CD8+ and CD3+ densities were quantified by immunohistochemistry in tissue microarray (TMA) cores, and their association with clinical outcome analysed by Cox regression. We validated our results using publicly available gene expression data in a pooled analysis of 1375 CRCs from seven independent series. Results In QUASAR2, intratumoural CD8+ was a stronger predictor of CRC recurrence than CD3+ and showed similar discriminative ability to both markers in combination. Pooled multivariable analysis of both trials showed increasing CD8+ density was associated with reduced recurrence risk independent of confounders including DNA mismatch repair deficiency, POLE mutation and chromosomal instability (multivariable hazard ratio [HR] for each two-fold increase = 0.92, 95%CI = 0.87–0.97, P = 3.6 × 10−3). This association was not uniform across risk strata defined by tumour and nodal stage: absent in low-risk (pT3,N0) cases (HR = 1.03, 95%CI = 0.87–1.21, P = 0.75), modest in intermediate-risk (pT4,N0 or pT1-3,N1-2) cases (HR = 0.92, 95%CI = 0.86–1.0, P = 0.046) and strong in high-risk (pT4,N1-2) cases (HR = 0.87, 95%CI = 0.79–0.97, P = 9.4 × 10−3); PINTERACTION = 0.090. Analysis of tumour CD8A expression in the independent validation cohort revealed similar variation in prognostic value across risk strata (PINTERACTION = 0.048). Conclusions The prognostic value of intratumoural CD8+ cell infiltration in stage II/III CRC varies across tumour and nodal risk strata. </p