A Note on the Integral Formulation of Einstein's Equations Induced on a Braneworld

We revisit the integral formulation (or Green's function approach) of Einstein's equations in the context of braneworlds. The integral formulation has been proposed independently by several authors in the past, based on the assumption that it is possible to give a reinterpretation of the local metric field in curved spacetimes as an integral expression involving sources and boundary conditions. This allows one to separate source-generated and source-free contributions to the metric field. As a consequence, an exact meaning to Mach's Principle can be achieved in the sense that only source-generated (matter fields) contributions to the metric are allowed for; universes which do not obey this condition would be non-Machian. In this paper, we revisit this idea concentrating on a Randall-Sundrum-type model with a non-trivial cosmology on the brane. We argue that the role of the surface term (the source-free contribution) in the braneworld scenario may be quite subtler than in the 4D formulation. This may pose, for instance, an interesting issue to the cosmological constant problem.Comment: 10 pages, no figures, accepted for publication in the General Relativity and Gravitation Journa

Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study

Parkinson plus diseases, comprising mainly progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are rare neurodegenerative conditions. We designed a double-blind randomized placebo-controlled trial of riluzole as a potential disease-modifying agent in Parkinson plus disorders (NNIPPS: Neuroprotection and Natural History in Parkinson Plus Syndromes). We analysed the accuracy of our clinical diagnostic criteria, and studied prognostic factors for survival. Patients with an akinetic-rigid syndrome diagnosed as having PSP or MSA according to modified consensus diagnostic criteria were considered for inclusion. The psychometric validity (convergent and predictive) of the NNIPPS diagnostic criteria were tested prospectively by clinical and pathological assessments. The study was powered to detect a 40% decrease in relative risk of death within PSP or MSA strata. Patients were randomized to riluzole or matched placebo daily and followed up to 36 months. The primary endpoint was survival. Secondary efficacy outcomes were rates of disease progression assessed by functional measures. A total of 767 patients were randomized and 760 qualified for the Intent to Treat (ITT) analysis, stratified at entry as PSP (362 patients) or MSA (398 patients). Median follow-up was 1095 days (range 249–1095). During the study, 342 patients died and 112 brains were examined for pathology. NNIPPS diagnostic criteria showed for both PSP and MSA excellent convergent validity with the investigators’ assessment of diagnostic probability (point-biserial correlation: MSA rpb = 0.93, P < 0.0001; PSP, rpb = 0.95, P < 0.0001), and excellent predictive validity against histopathology [sensitivity and specificity (95% CI) for PSP 0.95 (0.88–0.98) and 0.84 (0.77–0.87); and for MSA 0.96 (0.88–0.99) and 0.91 (0.86–0.93)]. There was no evidence of a drug effect on survival in the PSP or MSA strata (3 year Kaplan–Meier estimates PSP-riluzole: 0.51, PSP-placebo: 0.50; MSA-riluzole: 0.53, MSA-placebo: 0.58; P = 0.66 and P = 0.48 by the log-rank test, respectively), or in the population as a whole (P = 0.42, by the stratified-log-rank test). Likewise, rate of progression was similar in both treatment groups. There were no unexpected adverse effects of riluzole, and no significant safety concerns. Riluzole did not have a significant effect on survival or rate of functional deterioration in PSP or MSA, although the study reached over 80% power to detect the hypothesized drug effect within strata. The NNIPPS diagnostic criteria were consistent and valid. They can be used to distinguish between PSP and MSA with high accuracy, and should facilitate research into these conditions relatively early in their evolution

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects

Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases

In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is predominantly performed to exclude inflammatory diseases and to perform a risk assessment in dementive disorders by measurement of tau proteins and amyloid beta peptides. However, large scale data on basic findings of CSF routine parameters are generally lacking. The objective of the study was to define a normal reference spectrum of routine CSF parameters in neurodegenerative diseases. Routine CSF parameters (white cell count, lactate and albumin concentrations, CSF/serum quotients of albumin (Qalb), IgG, IgA, IgM, and oligoclonal IgG bands (OCB)) were retrospectively analyzed in an academic research setting. A total of 765 patients (Alzheimer’s disease (AD), Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), vascular dementia (VD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington’s disease (HD)) and non-demented control groups including a group of patients with muscular disorders (MD). The main outcome measures included statistical analyses of routine CSF parameters. Mildly elevated Qalb were found in a small percentage of nearly all subgroups and in a higher proportion of patients with PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients with neurodegenerative diseases without elevated cell counts; lactate levels were always normal. A slightly elevated Qalb was observed in a subgroup of patients with neurodegenerative diseases and does not exclude the diagnosis. Extensive elevation of routine parameters is not characteristic and should encourage a re-evaluation of the clinical diagnosis

Introduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67161/2/10.1177_0308275X9301300401.pd

Emergent research and priorities for shark and ray conservation

Over the past 4 decades there has been a growing concern for the conservation status of elasmobranchs (sharks and rays). In 2002, the first elasmobranch species were added to Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Less than 20 yr later, there were 39 species on Appendix II and 5 on Appendix I. Despite growing concern, effective conservation and management remain challenged by a lack of data on population status for many species, human−wildlife interactions, threats to population viability, and the efficacy of conservation approaches. We surveyed 100 of the most frequently published and cited experts on elasmobranchs and, based on ranked responses, prioritized 20 research questions on elasmobranch conservation. To address these questions, we then convened a group of 47 experts from 35 institutions and 12 countries. The 20 questions were organized into the following broad categories: (1) status and threats, (2) population and ecology, and (3) conservation and management. For each section, we sought to synthesize existing knowledge, describe consensus or diverging views, identify gaps, and suggest promising future directions and research priorities. The resulting synthesis aggregates an array of perspectives on emergent research and priority directions for elasmobranch conservation

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07