The International Mass Loading Service

The International Mass Loading Service computes four loadings: a) atmospheric pressure loading; b) land water storage loading; c) oceanic tidal loading; and d) non-tidal oceanic loading. The service provides to users the mass loading time series in three forms: 1) pre-computed time series for a list of 849 space geodesy stations; 2) pre-computed time series on the global 1deg x 1deg grid; and 3) on-demand Internet service for a list of stations and a time range specified by the user. The loading displacements are provided for the time period from 1979.01.01 through present, updated on an hourly basis, and have latencies 8-20 hours.Comment: 8 pages, 3 figures, to appear in the Proceedings of the Reference Frames for Applications in Geosciences Simposium, held in Luxemboug in October 201

Differences in the Active Endometrial Microbiota across Body Weight and Cancer in Humans and Mice

Obesity is a risk factor for endometrial cancer. The aim of this study was to determine whether actively replicating microbiota in the endometrium differ between obese vs. lean and cancer vs. benign states. We performed 16S rRNA amplicon sequencing on endometrial tissues from lean and obese women with and without endometrial cancer, and lean and obese mice. Results displayed human endometrial microbiota clustered into three community types (R = 0.363, p = 0.001). Lactobacillus was dominant in community type 1 (C1) while community type 2 (C2) had high levels of Proteobacteria and more cancer samples when compared to C1 (p = 0.007) and C3 (p = 0.0002). A significant increase in the prevalence of the C2 community type was observed across body mass index and cancer (χ2 = 14.24, p = 0.0002). The relative abundance of Lactobacillus was lower in cancer samples (p = 0.0043), and an OTU with 100% similarity to Lactobacillus iners was enriched in control samples (p = 0.0029). Mouse endometrial microbiota also clustered into three community types (R = 0.419, p = 0.001) which were not influenced by obesity. In conclusion, obesity and cancer are associated with community type prevalence in the human endometrium, and Lactobacillus abundance is associated with normal uterine histologies in humans and mice

Reminiscence therapy for dementia

BACKGROUND: This updated Cochrane Review of reminiscence therapy (RT) for dementia was first published in 1998, and last updated in 2005. RT involves the discussion of memories and past experiences with other people using tangible prompts such as photographs or music to evoke memories and stimulate conversation. RT is implemented widely in a range of settings using a variety of formats. OBJECTIVES: To assess the effects of RT on people living with dementia and their carers, taking into account differences in its implementation, including setting (care home, community) and modality (group, individual). SEARCH METHODS: We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's Specialized Register) on 6 April 2017 using the search term 'reminiscence.' SELECTION CRITERIA: We included all randomised controlled trials of RT for dementia in which the duration of the intervention was at least four weeks (or six sessions) and that had a 'no treatment' or passive control group. Outcomes of interest were quality of life (QoL), cognition, communication, behaviour, mood and carer outcomes. DATA COLLECTION AND ANALYSIS: Two authors (LOP and EF) independently extracted data and assessed risk of bias. Where necessary, we contacted study authors for additional information. We pooled data from all sufficiently similar studies reporting on each outcome. We undertook subgroup analysis by setting (community versus care home) and by modality (individual versus group). We used GRADE methods to assess the overall quality of evidence for each outcome. MAIN RESULTS: We included 22 studies involving 1972 people with dementia. Meta-analyses included data from 16 studies (1749 participants). Apart from six studies with risk of selection bias, the overall risk of bias in the studies was low.Overall, moderate quality evidence indicated RT did not have an important effect on QoL immediately after the intervention period compared with no treatment (standardised mean difference (SMD) 0.11, 95% confidence interval (CI) -0.12 to 0.33; I2= 59%; 8 studies; 1060 participants). Inconsistency between studies mainly related to the study setting. There was probably a slight benefit in favour of RT in care homes post-treatment (SMD 0.46, 95% CI 0.18 to 0.75; 3 studies; 193 participants), but little or no difference in QoL in community settings (867 participants from five studies).For cognitive measures, there was high quality evidence for a very small benefit, of doubtful clinical importance, associated with reminiscence at the end of treatment (SMD 0.11, 95% CI 0.00 to 0.23; 14 studies; 1219 participants), but little or no difference at longer-term follow-up. There was a probable slight improvement for individual reminiscence and for care homes when analysed separately, but little or no difference for community settings or for group studies. Nine studies included the widely used Mini-Mental State Examination (MMSE) as a cognitive measure, and, on this scale, there was high quality evidence for an improvement at the end of treatment (mean difference (MD) 1.87 points, 95% CI 0.54 to 3.20; 437 participants). There was a similar effect at longer-term follow-up, but the quality of evidence for this analysis was low (1.8 points, 95% CI -0.06 to 3.65).For communication measures, there may have been a benefit of RT at the end of treatment (SMD -0.51 points, 95% CI -0.97 to -0.05; I2= 62%; negative scores indicated improvement; 6 studies; 249 participants), but there was inconsistency between studies, related to the RT modality. At follow-up, there was probably a slight benefit of RT (SMD -0.49 points, 95% CI -0.77 to -0.21; 4 studies; 204 participants). Effects were uncertain for individual RT, with very low quality evidence available. For reminiscence groups, evidence of moderate quality indicated a probable slight benefit immediately (SMD -0.39, 95% CI -0.71 to -0.06; 4 studies; 153 participants), and at later follow-up. Community participants probably benefited at end of treatment and follow-up. For care home participants, the results were inconsistent between studies and, while there may be an improvement at follow-up, at the end of treatment the evidence quality was very low and effects were uncertain.Other outcome domains examined for people with dementia included mood, functioning in daily activities, agitation/irritability and relationship quality. There were no clear effects in these domains. Individual reminiscence was probably associated with a slight benefit on depression scales, although its clinical importance was uncertain (SMD -0.41, 95% CI -0.76 to -0.06; 4 studies; 131 participants). We found no evidence of any harmful effects on people with dementia.We also looked at outcomes for carers, including stress, mood and quality of relationship with the person with dementia (from the carer's perspective). We found no evidence of effects on carers other than a potential adverse outcome related to carer anxiety at longer-term follow-up, based on two studies that had involved the carer jointly in reminiscence groups with people with dementia. The control group carers were probably slightly less anxious (MD 0.56 points, 95% CI -0.17 to 1.30; 464 participants), but this result is of uncertain clinical importance, and is also consistent with little or no effect. AUTHORS' CONCLUSIONS: The effects of reminiscence interventions are inconsistent, often small in size and can differ considerably across settings and modalities. RT has some positive effects on people with dementia in the domains of QoL, cognition, communication and mood. Care home studies show the widest range of benefits, including QoL, cognition and communication (at follow-up). Individual RT is associated with probable benefits for cognition and mood. Group RT and a community setting are associated with probable improvements in communication. The wide range of RT interventions across studies makes comparisons and evaluation of relative benefits difficult. Treatment protocols are not described in sufficient detail in many publications. There have been welcome improvements in the quality of research on RT since the previous version of this review, although there still remains a need for more randomised controlled trials following clear, detailed treatment protocols, especially allowing the effects of simple and integrative RT to be compared

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points

Heterogeneity and the dynamics of technology adoption

We estimate the demand for a videocalling technology in the presence of both network effects and heterogeneity. Using a unique dataset from a large multinational firm, we pose and estimate a fully dynamic model of technology adoption. We propose a novel identification strategy based on post-adoption technology usage to disentangle equilibrium beliefs concerning the evolution of the network from observed and unobserved heterogeneity in technology adoption costs and use benefits. We find that employees have significant heterogeneity in both adoption costs and network benefits, and have preferences for diverse networks. Using our estimates, we evaluate a number of counterfactual adoption policies, and find that a policy of strategically targeting the right subtype for initial adoption can lead to a faster-growing and larger network than a policy of uncoordinated or diffuse adoption

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation

Urocortin protects chondrocytes from NO-induced apoptosis: a future therapy for osteoarthritis?

Osteoarthritis (OA) is characterized by a loss of joint mobility and pain resulting from progressive destruction and loss of articular cartilage secondary to chondrocyte death and/ or senescence. Certain stimuli including nitric oxide (NO) and the pro-inflammatory cytokine tumor necrosis factor α (TNF-α have been implicated in this chondrocyte death and the subsequent accelerated damage to cartilage. In this study, we demonstrate that a corticotrophin releasing factor (CRF) family peptide, urocortin (Ucn), is produced by a human chondrocyte cell line, C-20/A4, and acts both as an endogenous survival signal and as a cytoprotective agent reducing the induction of apoptosis by NO but not TNF-α when added exogenously. Furthermore, treatment with the NO donor S-nitroso-N-acetyl-D-L-penicillamine upregulates chondrocyte Ucn expression, whereas treatment with TNF-α does not. The chondroprotective effects of Ucn are abolished by both specific ligand depletion (with an anti-Ucn antibody) and by CRF receptor blockade with the pan-CRFR antagonist α-helical CRH(9-41). CRFR expression was confirmed by reverse transcription-PCR with subsequent amplicon sequence analysis and demonstrates that C-20/A4 cells express both CRFR1 and CRFR2, specifically CRFR1α and CRFR2β. Protein expression of these receptors was confirmed by western blotting. The presence of both Ucn and its receptors in these cells, coupled with the induction of Ucn by NO, suggests the existence of an endogenous autocrine/paracrine chondroprotective mechanism against stimuli inducing chondrocyte apoptosis via the intrinsic/mitochondrial pathway