Analysis of long term hydrological records to assess the changing regime and pathways in oil shale mining districts of North East Estonia

This paper documents long term (1923-2005) changes in surface drainage areas and run-off characteristics in two small to medium (100-1000 km2) rivers draining part of the Ordovician oil shale field of north east Estonia. The changing regime in the heavily mined catchments is contrasted with a morphologically similar reference catchment (River Keila) where there has been no mining activity. Coupling of flow regime with mining records (discharge rates and workings locations) is undertaken to assess the impact of expansion in oil shale mining through the mid to late 20th century on downstream flow regime and pathways. The study shows that during phases of intense mining, summer baseflow is between 53-72% higher than long term average baseflow in the Purtse catchment and between 66-92% higher in the smaller Pühajõgi catchment where the volumetric significance of mine discharges is greater. The Keila catchment does not show any significant change in summer baseflow during the study period suggesting that the changes in the Pühajõgi and Purtse are not controlled by climatic drivers. Assessment of mine flow records highlights the significant augmentation of baseflow in the mined catchments

What's Love Got to do with it: Role of oxytocin in trauma, attachment and resilience..

Oxytocin (OT) is a neurohypophysial hormone and neuropeptide produced by the hypothalamus and released by the pituitary gland. It has multiple physiological roles including stimulation of parturition and lactation, and promotion of pro-adaptive social behaviors necessary for mammalian survival. OT interacts with one receptor subtype: the OT receptor (OTR), which, upon stimulation, triggers different intracellular signal transduction cascades to mediate its physiological actions. Preclinical studies show that OT regulates social behaviors such as pair bonding, recognition and social interaction. It also coordinates the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of corticotrophin-releasing hormone. Further evidence suggests that OT plays an important role in regulating caloric intake and metabolism, and in maintaining electrolyte and cardiovascular homeostasis. OT is also involved in attenuating the neurophysiological and neurochemical effects of trauma on the brain and body by facilitating both physical attachment such as wound healing, and psychological/social attachment, thereby increasing resilience to subsequent traumatic events. Clinical trials have reported that intranasal administration of OT provides therapeutic benefits for patients diagnosed with traumatic stress-related diseases such as major depressive disorders and post-traumatic stress disorder. OT's therapeutic benefits may result from context-dependent interactions with key neural pathways (social, cognitive, and reward), neurotransmitters (dopamine, norepinephrine, serotonin, and endogenous opioids), and biomarkers (adrenocorticotropic hormone, cortisol, and dehydroepiandrosterone sulfate), that lead to a decrease in stress associated behaviors, and facilitate post-traumatic growth, ultimately leading to increased resilience, through improved social cohesion and attachment. OT induced-augmentation of physical and cognitive resilience may play a significant role in both the prevention of, and improved clinical outcomes for, traumatic stress-related disorders following either acute or enduring traumatic experiences

Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial

Background Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. Methods In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (= 50 years) and intended duration of antiviral prophylaxis after transplantation ( 3 to <= 6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials. gov (NCT01229267) and EudraCT (2010-020150-34). Findings Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2 . 4 years (SD 1.3) in the vaccine consistency lot group and 2.3 years (SD 1.3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32.9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91.9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63.8% (95% CI 48.4-74.6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0.2%, 95% CI -5.1 to 5.5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0.1%, -1.4 to 1.1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22.6%, 95% CI 18.5-26.6; p<0.0001). Interpretation This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. Funding Merck & Co., Inc. Copyright (C) 2018 Elsevier Ltd. All rights reserved