Studies Directed Toward Improving the Spatial Resolution of the Distribution of Plutonium in Bone

Of several methods which have been discussed for the improvement of resolution in fission fragment track detectors for neutron-induced autoradiography, emphasis had been on the use of absorber layers inserted between the sample and the detector. Scanning electron microscopy was shown to be beneficial for viewing only the entrance holes of fission fragment tracks in the detector foil. The primary disadvantage of using thick absorbers lies in the factor of 50 to 100 percent loss in sensitivity over bare detectors. One promising solution to this problem is the use of glass detectors with high critical angles, no absorbers, and short etching times. Such detectors gave the best resolution of any system tested (+-2 $mu$), though they suffered at fluences greater than 10$sup 16$ n/sub th/ cm$sup 2$ from high backgrounds as a result of their natural uranium content. Two samples of bone, each of 1 mg were dissolved in HNO$sub 3$ spiked with $sup 244$Pu, and analyzed for total $sup 239$Pu content in an isotopic abundance mass spectrometer. The $sup 239$Pu concentration was 1 ppm by weight; bones with 10 ppm of $sup 239$Pu are required, therefore, for neutron-induced autoradiography. Bones in suitable form for IMMA required only to be coated with a thin conductive coating of gold. In a fast scan mode, all elements were searched in 200 x 200 areas. Good quality micrographs were obtained showing Na, K, Ca, and P as major constituents with minor elements present, such as Cr and Fe. (CH

Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.

Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer.Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63).Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%).Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects

Comparative study of combustion product emissions of Pakistani coal briquettes and traditional Pakistani domestic fuels

A comparative emissions study was conducted on combustion products of various solid domestic cooking fuels; the objective was to compare relative levels of organic and inorganic toxic emissions from traditional Pakistani fuels (wood, wood charcoal, and dried animal dung) with manufactured low-rank coal briquettes (Lakhra and Sor- Range coals) under conditions simulating domestic cooking. A small combustion shed 12 m[sup 3] internal volume, air exchange rate 14 h[sup [minus]1] was used to simulate south Asian cooking rooms. 200-g charges of the various fuels were ignited in an Angethi stove located inside the shed, then combusted to completion; effluents from this combustion were monitored as a function of time. Measurements were made of respirable particulates, volatile and semi-volatile organics, CO, SO[sub 2], and NO[sub x]. Overall it appears that emissions from coal briquettes containing combustion amendments (slaked lime, clay, and potassium nitrate oxidizer) are no greater than emissions from traditional fuels, and in some cases are significantly lower; generally, emissions are highest for all fuels in the early stages of combustion

‘Stepping away from the computer and into the sweats': The construction and negotiation of exercise identities in a Norwegian public company

While research has found that a developed exercise identity enables individuals to view exercise participation as self- reinforcing, the social barriers to such exercise identity development and participation have not been fully addressed. The subsequent aim of this study was to explore some of the social complexities at play in terms of how company employees construct and manage their exercise identities within a work place setting. A case-study method was used to address the research issue over a nine-month period. The case to be studied included a sample of 72 employees from a Norwegian public company who participated in an on-going work-based exercise programme called ‘Exercise for all’. The principal means of data collection comprised participant observation, individual interviews and exercise logbooks. The data were subject to inductive analysis. The primary barriers to exercise participation included high levels of social comparison in a competitive working context, particularly in relation to ‘competent colleagues’, and feelings of guilt associated with partaking in ‘recreational’ activities during work hours. Strategies engaged with to overcome and negotiate such obstacles included justifying participation through a health-related discourse, and constructing a more distinct ‘worker-exerciser’ identity

Impact of financial inclusion in low- and middle-income countries: a systematic review of reviews

Financial inclusion programmes seek to increase access to financial services such as credit, savings, insurance and money transfers and so allow poor and low-income households in low- and middle-income countries to enhance their welfare, grasp opportunities, mitigate shocks, and ultimately escape poverty. This systematic review of reviews assesses the evidence on economic, social, behavioural and gender-related outcomes from financial inclusion. It collects and appraises all of the existing meta-studies - that is systematic reviews and meta-analyses - of the impact of financial inclusion. The authors first analyse the strength of the methods used in those meta-studies, then synthesise the findings from those that are of a sufficient quality, and finally, report the implications for policy, programming, practice and further research arising from the evidence. Eleven studies are included in the analysis

Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma

The mitochondrial genome (mtDNA) encodes essential machinery for oxidative phosphorylation and metabolic homeostasis. Tumor mtDNA is among the most somatically mutated regions of the cancer genome, but whether these mutations impact tumor biology is debated. We engineered truncating mutations of the mtDNA-encoded complex I gene, Mt-Nd5, into several murine models of melanoma. These mutations promoted a Warburg-like metabolic shift that reshaped tumor microenvironments in both mice and humans, consistently eliciting an anti-tumor immune response characterized by loss of resident neutrophils. Tumors bearing mtDNA mutations were sensitized to checkpoint blockade in a neutrophil-dependent manner, with induction of redox imbalance being sufficient to induce this effect in mtDNA wild-type tumors. Patient lesions bearing >50% mtDNA mutation heteroplasmy demonstrated a response rate to checkpoint blockade that was improved by ~2.5-fold over mtDNA wild-type cancer. These data nominate mtDNA mutations as functional regulators of cancer metabolism and tumor biology, with potential for therapeutic exploitation and treatment stratification

An integrated framework for assessing coastal community vulnerability across cultures, oceans and scales.

Coastal communities are some of the most at-risk populations with respect to climate change impacts. It is therefore important to determine the vulnerability of such communities to co-develop viable adaptation options. Global efforts to address this issue include international scientific projects, such as Global Learning for Local Solutions (GULLS), which focuses on five fast warming regions of the southern hemisphere and aims to provide an understanding of the local scale processes influencing community vulnerability that can then be up-scaled to regional, country and global levels. This paper describes the development of a new social and ecological vulnerability framework which integrates exposure, sensitivity and adaptive capacity with the social livelihoods and food security approaches. It also measures community flexibility to understand better the adaptive capacity of different levels of community organization. The translation of the conceptual framework to an implementable method is described and its application in a number of “hotspot” countries, where ocean waters are warming faster than the rest of the world, is presented. Opportunities for cross-cultural comparisons to uncover similarities and differences in vulnerability and adaptation patterns among the study’s coastal communities, which can provide accelerated learning mechanisms to other coastal regions, are highlighted. The social and ecological framework and the associated survey approach allow for future integration of local-level vulnerability data with ecological and oceanographic models