Serum vitamin D decreases during chemotherapy: an Australian prospective cohort study

Background and Objectives: Vitamin D plays an important role in bone and muscle function, and cell prolifera-tion. The impact of chemotherapy and associated behavioural changes such as fatigue and sun avoidance on vit-amin D (25(OH) D) is unknown. This study aims to evaluate variations in serum vitamin D during chemotherapy and the predictive value of latitude, season and pre-existing vitamin D deficiency. Methods and Study Design: A 12-week prospective cohort study was conducted in chemotherapy-naïve patients in two Australian locations with different sun exposure. Vitamin D deficiency was defined as ≤ 25 nmol/L and insufficiency 26-50 nmol/L 25(OH) D. Demographics, chemotherapy regimen, nutritional status, sun exposure, geographic location, and sea-son were collected at baseline, 6 and 12 weeks after commencing chemotherapy. Results: Eighty-five patients (μ55.3±13.4 years of age; 49% female) were recruited, 96% Caucasian. Fifty-four patients were treated with cura-tive intent (mostly for breast [n=29] or colorectal [n=12] cancers). At baseline, 10 patients were vitamin D defi-cient and 33 were insufficient. Mean serum 25(OH) D (nmol/L) was higher at latitude -27.5o (Brisbane) than lati-tude -34.9o (Adelaide) (μ61.9±22.1 vs μ42.2±19.2, p < 0.001) and varied according to season (spring: μ46.9±20.3, summer: μ50.8±18.2, autumn: μ76.4±25.2, winter: μ36.5±15.7, p < 0.001). Serum 25(OH) D decreased with chemotherapy (baseline: μ49.2±22.3, 6-weeks: μ40.9±19.0, 12-weeks: μ45.9±19.7, p=0.05), with a significant and more rapid decline in winter and autumn (p=0.03). Conclusions: Chemotherapy is associated with a decrease in serum vitamin D, particularly during winter and autumn. Investigations into the underlying mechanism and as-sociated potential outcomes with this decrease requires further investigation

Walk on the Wild Side: Estimating the Global Magnitude of Visits to Protected Areas

How often do people visit the world’s protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don’t know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world’s terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y—of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US$250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation.This study was supported by The Natural Capital Project (http://www.naturalcapitalproject.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002074

Walk on the wild side: estimating the global magnitude of visits to protected areas.

How often do people visit the world's protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don't know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world's terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y-of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US$250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation.This study was supported by The Natural Capital Project (http://www.naturalcapitalproject.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002074

Adaptation Space: Surviving Non-Maskable Failures

Some failures cannot be masked by redundancies, because an unanticipated situation occurred, because fault-tolerance measures were not adequate, or because there was a security breach (which is not amenable to replication). Applications that wish to continue to offer some service despite nonmaskable failure must adapt to the loss of resources. When numerous combinations of non-maskable failure modes are considered, the set of possible adaptations becomes complex. This paper presents adaptation spaces, a formalism for navigating among combinations of adaptations. An adaptation space describes a collection of possible adaptations of a software component or system, and provides a uniform way of viewing a group of alternative software adaptations. Adaptation spaces describe the different means for monitoring the conditions that different adaptations depend on, and the particular configurations through which an adaptive application navigate. Our goal is to use adaptation spaces to provide survivable services to applications despite non-maskable failures such as malicious attacks. We present the basic concepts concerning adaptation spaces, with examples. We then present a formal model for reasoning about and selecting alternative adaptations, allowing developers of survivable application to automate their system’s adaptive behavior

Structural basis for arginine glycosylation of host substrates by bacterial effector proteins

The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens

Monitoring and dietary risk assessment of 81 pesticide residues in 11 local agricultural products from the 3 largest cities of Cameroon

This study monitored 81 pesticides residues in 160 samples of 11 dry agricultural products collected in the 3 largest cities of Cameroon, extracted using QuEChERS method and analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Residues of 58 (71.6%) compounds were found in the samples, the most distributed pesticides were Imazalil, Triadimenol and Pyrimethanil, and those with the highest average concentrations were Cymoxanil, Thiamethoxam and Thifensulfuron. Half of the positive pesticides were above their European Union maximum residue limits (MRLs) among which Carbaryl, Carbofuran, Malathion, Metalaxyl and Propoxur are pesticides banned in the country. All the 11 food items contained pesticides, the highest contamination rates (12.8%–5.0%) were found in white pepper, maize, Egusi seeds and groundnuts, while groundnuts, Egusi seeds, maize and soybeans showed the highest residue concentrations (1.46–1.37 mg/kg). Pesticide contamination rates were similar in the 3 sampling cities, but Bafoussam and Yaounde had more samples above the MRLs than Douala. Using the food consumption data for Cameroon from the recent Sub-Saharan Africa Total Diet Study, dietary exposure was calculated and potential health risk of Cameroonian consumers was evaluated. Hazard quotient of Carbofuran in groundnuts was 22% above the safe value, the remaining food items could be considered safe for individual pesticide residues, although Triazophos and Metribuzin in maize were of concern. Groundnuts (0.531) and maize (0.443) showed high hazard index, with 17 highly contributing compounds, but there is no reason to be concerned about cumulative exposure to residues from the food items. While the food items are in general safe to eat, to minimize the increasing human health risk of consumers and ensure approval of Cameroon export produces on international market, this study suggests that authorities must regulate the usage of agrochemicals, strengthen the controls for effective implementation of the pesticide bans and implement strong control of obsolete pesticide stocks in the country

Maternal Alcohol Consumption During Pregnancy and Physical Outcomes up to 5 Years of Age: A Longitudinal Study

Aim To examine whether alcohol exposure in pregnancy affects weight and head circumference (HC) at birth and 5 years, and whether these effects are independent of cigarette exposure in pregnancy and social disadvantage. Study design The Mater-University Study of Pregnancy (MUSP) involves a prospective cohort of 8556 mothers who were enrolled at first antenatal visit. The quantity and frequency of alcohol consumption in early and late pregnancy and a measure of binge drinking in early pregnancy were recorded. Weight and HC were measured on children seen at birth and at 5 years. Level of cigarette use in early pregnancy and maternal age and level of education and family income were also measured. Results Light and moderate alcohol consumption in early or later pregnancy had no independent effects on weight or HC at birth or 5 years. Binge drinking in early pregnancy was not associated with restricted HC, and there was no effect modification by concurrent cigarette use in early pregnancy. An apparent effect of alcohol in late pregnancy on birth weight was due to confounding by cigarette use, with social risk being an independent predictor. Conclusion Alcohol ingestion up to moderate levels in pregnancy was not associated with deficits in either weight or HC at birth or at 5 years

Intra-oral compartment pressures: a biofunctional model and experimental measurements under different conditions of posture

Oral posture is considered to have a major influence on the development and reoccurrence of malocclusion. A biofunctional model was tested with the null hypotheses that (1) there are no significant differences between pressures during different oral functions and (2) between pressure measurements in different oral compartments in order to substantiate various postural conditions at rest by intra-oral pressure dynamics. Atmospheric pressure monitoring was simultaneously carried out with a digital manometer in the vestibular inter-occlusal space (IOS) and at the palatal vault (sub-palatal space, SPS). Twenty subjects with normal occlusion were evaluated during the open-mouth condition (OC), gently closed lips (semi-open compartment condition, SC), with closed compartments after the generation of a negative pressure (CCN) and swallowing (SW). Pressure curve characteristics were compared between the different measurement phases (OC, SC, CCN, SW) as well as between the two compartments (IOS, SPS) using analysis of variance and Wilcoxon matched-pairs tests adopting a significance level of α = 0.05. Both null hypotheses were rejected. Average pressures (IOS, SPS) in the experimental phases were 0.0, −0.08 (OC); −0.16, −1.0 (SC); −48.79, −81.86 (CCN); and −29.25, −62.51 (SW) mbar. CCN plateau and peak characteristics significantly differed between the two compartments SPS and IOS. These results indicate the formation of two different intra-oral functional anatomical compartments which provide a deeper understanding of orofacial biofunctions and explain previous observations of negative intra-oral pressures at rest