Mass balance re-analysis of Findelengletscher, Switzerland; benefits of extensive snow accumulation measurements

A re-analysis is presented here of a 10 year mass balance series at Findelengletscher, a temperate mountain glacier in Switzerland. Calculating glacier-wide mass balance from the set of glaciological point balance observations using conventional approaches, such as the profile or contour method, resulted in significant deviations from the reference value given by the geodetic mass change over a 5 year period. This is attributed to the sparsity of observations at high elevations and to the inability of the evaluation schemes to adequately estimate accumulation in unmeasured areas. However, measurements of winter mass balance were available for large parts of the study period from snow probings and density pits. Complementary surveys by helicopter-borne ground-penetrating radar (GPR) were conducted in three consecutive years. The complete set of seasonal observations was assimilated using a distributed mass balance model. This model-based extrapolation revealed a substantial mass loss at Findelengletscher of −0.43 m w.e.a⁻¹ between 2004 and 2014, while the loss was less pronounced for its former tributary, Adlergletscher (−0.30 m w.e.a⁻¹). For both glaciers, the resulting time series were within the uncertainty bounds of the geodetic mass change. We show that the model benefited strongly from the ability to integrate seasonal observations. If no winter mass balance measurements were available and snow cover was represented by a linear precipitation gradient, the geodetic mass balance was not matched. If winter balance measurements by snow probings and snow density pits were taken into account, the model performance was substantially improved but still showed a significant bias relative to the geodetic mass change. Thus, the excellent agreement of the model-based extrapolation with the geodetic mass change was owed to an adequate representation of winter accumulation distribution by means of extensive GPR measurements

Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease.

OBJECTIVE: Congenital heart disease (CHD) is the most frequent birth defect worldwide. The number of adult patients with CHD, now referred to as ACHD, is increasing with improved surgical and treatment interventions. However the mechanisms whereby ACHD predisposes patients to heart dysfunction are still unclear. ACHD is strongly associated with metabolic syndrome, but how ACHD interacts with poor modern lifestyle choices and other comorbidities, such as hypertension, obesity, and diabetes, is mostly unknown. METHODS: We used a newly characterized mouse genetic model of ACHD to investigate the consequences and the mechanisms associated with combined obesity and ACHD predisposition. Metformin intervention was used to further evaluate potential therapeutic amelioration of cardiac dysfunction in this model. RESULTS: ACHD mice placed under metabolic stress (high fat diet) displayed decreased left ventricular ejection fraction. Comprehensive physiological, biochemical, and molecular analysis showed that ACHD hearts exhibited early changes in energy metabolism with increased glucose dependence as main cardiac energy source. These changes preceded cardiac dysfunction mediated by exposure to high fat diet and were associated with increased disease severity. Restoration of metabolic balance by metformin administration prevented the development of heart dysfunction in ACHD predisposed mice. CONCLUSIONS: This study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise the prospect for a translational reassessment of ACHD presentation in the clinic

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Basic Atomic Physics

Contains reports on five research projects.National Science Foundation Grant PHY 89-19381National Science Foundation Grant PHY 92-21489U.S. Navy - Office of Naval Research Grant N00014-90-J-1322Joint Services Electronics Program Contract DAAL03-92-C-0001National Science Foundation Grant PHY 89-21769U.S. Army - Office of Scientific Research Grant DAAL03-92-G-0229U.S. Navy - Office of Naval Research Grant N00014-89-J-1207U.S. Navy - Office of Naval Research Grant N00014-90-J-164