Food security, farming, and climate change to 2050: Scenarios, results, policy options

As the global population grows and incomes in poor countries rise, so too, will the demand for food, placing additional pressure on sustainable food production. Climate change adds a further challenge, as changes in temperature and precipitation threaten agricultural productivity and the capacity to feed the world's population. This study assesses how serious the danger to food security might be and suggests some steps policymakers can take to remedy the situation.global food security, Climate change, Food prices, Agricultural productivity,

Photoselektive Vaporisation der Prostata: Erfahrungen mit Prostataadenomen >80cm3

Zusammenfassung: Hintergrund: Wir berichten über unsere Erfahrungen mit der photoselektiven Vaporisation der Prostata (PVP) bei Patienten mit symptomatischer benigner Prostatahyperplasie (BPH) und Prostataadenomen >80cm3. Patienten und Methode: 201Patienten mit BPH wurden in die Studie eingeschlossen; 51 (25,4%) Patienten hatten ein Prostatavolumen >80cm3 und 150 (74,6%) Patienten ein Volumen 80cm3 stellt die PVP eine durchführbare Therapieoption da

Climate change: Impact on agriculture and costs of adaptation

"The Challenge The unimpeded growth of greenhouse gas emissions is raising the earth’s temperature. The consequences include melting glaciers, more precipitation, more and more extreme weather events, and shifting seasons. The accelerating pace of climate change, combined with global population and income growth, threatens food security everywhere. Agriculture is extremely vulnerable to climate change. Higher temperatures eventually reduce yields of desirable crops while encouraging weed and pest proliferation. Changes in precipitation patterns increase the likelihood of short-run crop failures and long-run production declines. Although there will be gains in some crops in some regions of the world, the overall impacts of climate change on agriculture are expected to be negative, threatening global food security. Populations in the developing world, which are already vulnerable and food insecure, are likely to be the most seriously affected. In 2005, nearly half of the economically active population in developing countries—2.5 billion people—relied on agriculture for its livelihood. Today, 75 percent of the world’s poor live in rural areas. This Food Policy Report presents research results that quantify the climate-change impacts mentioned above, assesses the consequences for food security, and estimates the investments that would offset the negative consequences for human well-being. This analysis brings together, for the first time, detailed modeling of crop growth under climate change with insights from an extremely detailed global agriculture model, using two climate scenarios to simulate future climate. The results of the analysis suggest that agriculture and human well-being will be negatively affected by climate change: * In developing countries, climate change will cause yield declines for the most important crops. South Asia will be particularly hard hit. * Climate change will have varying effects on irrigated yields across regions, but irrigated yields for all crops in South Asia will experience large declines. * Climate change will result in additional price increases for the most important agricultural crops–rice, wheat, maize, and soybeans. Higher feed prices will result in higher meat prices. As a result, climate change will reduce the growth in meat consumption slightly and cause a more substantial fall in cereals consumption. * Calorie availability in 2050 will not only be lower than in the no–climate-change scenario—it will actually decline relative to 2000 levels throughout the developing world. * By 2050, the decline in calorie availability will increase child malnutrition by 20 percent relative to a world with no climate change. Climate change will eliminate much of the improvement in child malnourishment levels that would occur with no climate change. * Thus, aggressive agricultural productivity investments of US$7.1–7.3 billion are needed to raise calorie consumption enough to offset the negative impacts of climate change on the health and well-being of children." from TextAdaptation, Agriculture, Climate change, Developing countries, food security,

Abnormal brain state distribution and network connectivity in a SYNGAP1 rat model

Mutations in the SYNGAP1 gene are one of the common predictors of neurodevelopmental disorders, commonly resulting in individuals developing autism, intellectual disability, epilepsy, and sleep deficits. EEG recordings in neurodevelopmental disorders show potential to identify clinically translatable biomarkers to both diagnose and track the progress of novel therapeutic strategies, as well as providing insight into underlying pathological mechanisms. In a rat model of SYNGAP1 haploinsufficiency in which the exons encoding the calcium/lipid binding and GTPase-activating protein domains have been deleted (Syngap(+/Δ−GAP)), we analysed the duration and occurrence of wake, non-rapid eye movement and rapid eye movement brain states during 6 h multi-electrode EEG recordings. We find that although Syngap(+/Δ−GAP) animals spend an equivalent percent time in wake and sleep states, they have an abnormal brain state distribution as the number of wake and non-rapid eye movement bouts are reduced and there is an increase in the average duration of both wake and non-rapid eye movement epochs. We perform connectivity analysis by calculating the average imaginary coherence between electrode pairs at varying distance thresholds during these states. In group averages from pairs of electrodes at short distances from each other, a clear reduction in connectivity during non-rapid eye movement is present between 11.5 Hz and 29.5 Hz, a frequency range that overlaps with sleep spindles, oscillatory phenomena thought to be important for normal brain function and memory consolidation. Sleep abnormalities were mostly uncorrelated to the electrophysiological signature of absence seizures, spike and wave discharges, as was the imaginary coherence deficit. Sleep spindles occurrence, amplitude, power and spread across multiple electrodes were not reduced in Syngap(+/Δ−GAP) rats, with only a small decrease in duration detected. Nonetheless, by analysing the dynamic imaginary coherence during sleep spindles, we found a reduction in high-connectivity instances between short-distance electrode pairs. Finally comparing the dynamic imaginary coherence during sleep spindles between individual electrode pairs, we identified a group of channels over the right somatosensory, association and visual cortices that have a significant reduction in connectivity during sleep spindles in mutant animals. This matched a significant reduction in connectivity during spindles when averaged regional comparisons were made. These data suggest that Syngap(+/Δ−GAP) rats have altered brain state dynamics and EEG connectivity, which may have clinical relevance for SYNGAP1 haploinsufficiency in humans

Face valid phenotypes in a mouse model of the most common mutation in EEF1A2 related neurodevelopmental disorder, E122K

De novo heterozygous missense mutations in EEF1A2, encoding neuromuscular translation-elongation factor eEF1A2, are associated with developmental and epileptic encephalopathies. We used CRISPR/Cas9 to recapitulate the most common mutation, E122K, in mice. Although E122K heterozygotes were not observed to have convulsive seizures, they exhibited frequent electrographic seizures and EEG abnormalities, transient early motor deficits and growth defects. Both E122K homozygotes and Eef1a2-null mice developed progressive motor abnormalities, with E122K homozygotes reaching humane endpoints by P31. The null phenotype is driven by progressive spinal neurodegeneration; however, no signs of neurodegeneration were observed in E122K homozygotes. The E122K protein was relatively stable in neurons yet highly unstable in skeletal myocytes, suggesting that the E122K/E122K phenotype is instead driven by loss of function in muscle. Nevertheless, motor abnormalities emerged far earlier in E122K homozygotes than in nulls, suggesting a toxic gain of function and/or a possible dominant-negative effect. This mouse model represents the first animal model of an EEF1A2 missense mutation with face-valid phenotypes and has provided mechanistic insights needed to inform rational treatment design.</p

Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1epileptic encephalopathy

Dynamin-1 is a large GTPase with an obligatory role in synaptic vesicle endocytosis at mammalian nerve terminals. Heterozygous missense mutations in the dynamin-1 gene (DNM1) cause a novel form of epileptic encephalopathy, with pathogenic mutations clustering within regions required for its essential GTPase activity. We reveal the most prevalent pathogenic DNM1 mutation, R237W, disrupts dynamin-1 enzyme activity and endocytosis when overexpressed in central neurons. To determine how this mutation impacted cell, circuit and behavioural function, we generated a mouse carrying the R237W mutation. Neurons from heterozygous mice display dysfunctional endocytosis, in addition to altered excitatory neurotransmission and seizure-like phenotypes. Importantly, these phenotypes are corrected at the cell, circuit and in vivo level by the drug, BMS-204352, which accelerates endocytosis. Here, we demonstrate a credible link between dysfunctional endocytosis and epileptic encephalopathy, and importantly reveal that synaptic vesicle recycling may be a viable therapeutic target for monogenic intractable epilepsies.<br/

Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer’s Disease

Abstract Network hyperexcitability is a feature of Alzheimer’ disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APPNL/F). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APPNL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD

ProCOC: The prostate cancer outcomes cohort study

BACKGROUND: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study. METHODS/DESIGN: This is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future. DISCUSSION: We presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer

Retroperitoneoscopy-Assisted Cryoablation of Renal Tumors Using Multiple 1.5 mm Ultrathin Cryoprobes: A Preliminary Report

Abstract Objectives: Laparoscopic cryoablation has recently been proposed as a minimally invasive nephron-sparing treatment for selected patients. We report on our experience with a retroperitoneoscopic technique using multiple ultrathin cryoprobes. Methods: Seven patients underwent retroperitoneoscopic renal cryoablation for solid renal masses. Mean tumor size on the CT scan was 2.6 (1.5-3.5) cm. A double freeze-thaw cycle of renal cryoablation was performed under realtime ultrasound monitoring using a total of six 1.5-mm cryoprobes simultaneously. Results: Cryoablation was technically successful in all patients without any need for conversion. Mean duration of surgery was 161 (130-195) minutes and mean blood loss was 107 (50-250) ml. Perioperative biopsy of the tumor confirmed renal cell carcinoma in four patients and angiomyolipoma in two patients; it was inconclusive in one case. Mean follow-up for 13.6 (4-22) months showed no evidence of residual tumor or recurrence. Conclusions: Retroperitoneoscopy-assisted cryosurgical ablation using multiple ultrathin 1.5-mm cryoprobes is a minimally invasive treatment that is suitable to treat small renal tumors.

Effectiveness of Air Filters and Air Cleaners in Allergic Respiratory Diseases: A Review of the Recent Literature

Air filtration is frequently recommended as a component of environmental control measures for patients with allergic respiratory disease. Residential air filtration can be provided by whole house filtration via the home’s heating, ventilation, or air conditioning system, by portable room air cleaners, or a combination of the two. Appliances to filter the sleep breathing zone also have been developed. High-efficiency whole house filtration, high-efficiency particulate air sleep zone air filtration, and high-efficiency particulate air room air cleaners all appear to provide various degrees of benefit. Recent studies of various types of filtration, used alone or as part of more comprehensive environmental control measures, are reviewed