Modelled ocean changes at the Plio-Pleistocene transition driven by Antarctic ice advance

The Earth underwent a major transition from the warm climates of the Pliocene to the Pleistocene ice ages between 3.2 and 2.6 million years ago. The intensification of Northern Hemisphere Glaciation is the most obvious result of the Plio-Pleistocene transition. However, recent data show that the ocean also underwent a significant change, with the convergence of deep water mass properties in the North Pacific and North Atlantic Ocean. Here we show that the lack of coastal ice in the Pacific sector of Antarctica leads to major reductions in Pacific Ocean overturning and the loss of the modern North Pacific Deep Water (NPDW) mass in climate models of the warmest periods of the Pliocene. These results potentially explain the convergence of global deep water mass properties at the Plio-Pleistocene transition, as Circumpolar Deep Water (CDW) became the common source

Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence

<p>Abstract</p> <p>Background</p> <p>Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.</p> <p>Methods</p> <p>We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.</p> <p>Results</p> <p>Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.</p> <p>Conclusion</p> <p>A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.</p

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

ICAR: endoscopic skull‐base surgery

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Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Mid-Pliocene climate change amplified by a switch in Indonesian subsurface throughflow

The tectonically driven closure of tropical seaways during the Pliocene epoch (approx5–2 million years (Myr) ago) altered ocean circulation and affected the evolution of climate. Plate tectonic reconstructions show that the main reorganization of one such seaway, the Indonesian Gateway, occurred between 4 and 3 Myr ago. Model simulations have suggested that this would have triggered a switch in the source of waters feeding the Indonesian throughflow into the Indian Ocean, from the warm salty waters of the South Pacific Ocean to the cool and relatively fresh waters of the North Pacific Ocean. Here we use paired measurements of the delta18O and Mg/Ca ratios of planktonic foraminifera to reconstruct the thermal structure of the eastern tropical Indian Ocean from 5.5 to 2 Myr ago. We find that sea surface conditions remained relatively stable throughout the interval, whereas subsurface waters freshened and cooled by about 4 °C between 3.5 and 2.95 Myr ago. We suggest that the restriction of the Indonesian Gateway led to the cooling and shoaling of the thermocline in the tropical Indian Ocean. We conclude that this tectonic reorganization contributed to the global shoaling of the thermocline recorded during the Pliocene epoch, possibly contributing to the development of the equatorial eastern Pacific cold tongue

Pediatric multiple sclerosis in Venezuela

OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS). METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%), brainstem/cerebellum and spinal cord affectation (27.6%), headache (26%). Less frequent symptoms were sensory symptoms (8%) and optic neuritis (7%). DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela

Fossil proxies of near-shore sea surface temperatures and seasonality from the late Neogene Antarctic shelf

We evaluate the available palaeontological and geochemical proxy data from bivalves, bryozoans, silicoflagellates, diatoms and cetaceans for sea surface temperature (SST) regimes around the nearshore Antarctic coast during the late Neogene. These fossils can be found in a number of shallow marine sedimentary settings from three regions of the Antarctic continent, the northern Antarctic Peninsula, the Prydz Bay region and the western Ross Sea. Many of the proxies suggest maximum spring–summer SSTs that are warmer than present by up to 5 °C, which would result in reduced seasonal sea ice. The evidence suggests that the summers on the Antarctic shelf during the late Neogene experienced most of the warming, while winter SSTs were little changed from present. Feedbacks from changes in summer sea ice covermay have driven much of the lateNeogene ocean warming seen in stratigraphic records. Synthesized late Neogene and earliest Quaternary Antarctic shelf proxy data are compared to the multi-model SST estimates of the Pliocene Model Intercomparison Project (PlioMIP) Experiment 2. Despite the fragmentary geographical and temporal context for the SST data, comparisons between the SSTwarming in each of the three regions represented in the marine palaeontological record of theAntarctic shelf and the PlioMIP climate simulations show a good concordance