An assessment of the potential impacts of climate change on the freshwater habitats of Indiana, U.S.A.

Recent climate-driven, physico-chemical changes documented in aquatic systems throughout the world are expected to intensify in the future. Specifically, changes in key environmental attributes of aquatic systems, such as water quantity, clarity, temperatures, ice cover, seasonal flow regimes, external loading, and oxygen content, will undoubtedly have a broad set of direct and indirect ecological consequences. Some anticipated impacts may be similar across different aquatic ecosystems, while others may be system-specific. Here, we review the potential effects of climatic changes for different freshwater habitats within the state of Indiana, USA, a Midwestern state with diverse land and water features. Given this heterogeneity and that the state is among the southernmost states of the US Midwest, evaluation of freshwater habitats of Indiana provides a useful perspective on potential impacts of climate change. In our study, we first review expected or anticipated changes to physico-chemical and habitat conditions in wetlands, lotic systems, small glacial lakes and Lake Michigan. We then highlight anticipated responses of select aquatic biota to these changes. We describe how climatic changes may interact with other anthropogenic stressors affecting freshwater habitats and consider the potential for evolutionary adaptation of freshwater aquatic organisms to mediate any responses. Given anticipated changes, we suggest aquatic ecosystem managers take a precautionary approach broadly applicable in temperate regions to (a) conserve a diversity of aquatic habitats, (b) enhance species diversity and both inter- and intra-population genetic variation, and (c) limit stressors which may exacerbate the risk of decline for aquatic biota

Efficacy of Fluoxetine, Riluzole and Amiloride in treating neuropathic pain associated with secondary progressive multiple sclerosis. Pre-specified analysis of the MS-SMART double-blind randomised placebo-controlled trial

BACKGROUND: Evidence-based treatment of pain in people with MS presents a major unmet need. OBJECTIVE: We aimed to establish if use of Fluoxetine, Riluzole or Amiloride improved neuropathic pain outcomes in comparison to placebo, in adults with secondary progressive MS participating in a trial of these putative neuroprotectants. METHODS: In pre-specified secondary analyses of the MS SMART phase-2b double-blind randomised controlled trial (NCT01910259), we analyzed reports of neuropathic pain, overall pain, and pain interference. Multivariate analyses included adjustment for baseline pain severity. Additionally, we explored associations of pain severity with clinical and MRI brain imaging variables. RESULTS: 445 Participants were recruited from 13 UK neuroscience centres. We found no statistically significant benefit of active intervention on any rating of neuropathic pain, or pain overall. Compared to placebo, adjusted mean difference in pain intensity was 0.38 (positive values favouring placebo, 95%CI -0.30 to 1.07, p = 0.27) for Amiloride; 0.52 (-0.17 to 1.22, p = 0.14) for Fluoxetine; and 0.40 (-0.30 to 1.10, p = 0.26) for Riluzole. Pain severity was positively correlated with depressive symptoms (Spearman correlation 0.19, 95%CI 0.10-0.28) and fatigue (Rho 0.30, 95%CI 0.20-0.39). CONCLUSION: Use of Fluoxetine, Riluzole or Amiloride was not associated with improvement in neuropathic pain symptoms, in comparison to placebo

Board of Regents

This report, fifteenth of an annual series, describes 1993 mineral, oil and gas, and geothermal activities and accomplishments in Nevada: production statistics, exploration and development including drilling for petroleum and geothermal resources, discoveries of orebodies, new mines opened, and expansion and other activities of existing mines. Statistics of known gold and silver deposits, and directories of mines and mills are included. For more information contact

NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system

BACKGROUND: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample. METHODOLOGY/PRINCIPAL FINDINGS: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity. CONCLUSIONS/SIGNIFICANCE: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes

Cardiac and vascular structure and function parameters do not improve with alternate nightly home hemodialysis: An interventional cohort study

Background: Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)