ischemia-reperfusion injury (IRI) after hemorrhage is potentiated by aortic occlusion or resuscitative endovascular balloon occlusion of the aorta (REBOA). Given the central role of mitochondrial ...injury in shock, we hypothesized that Elamipretide, a peptide that protects mitochondria, would mitigate IRI after hemorrhagic shock and REBOA. Twelve pigs were subjected to hemorrhagic shock and 45 min of REBOA. After 25 min of REBOA, animals received either saline or Elamipretide. Animals were transfused with autologous blood during balloon deflation, and pigs were resuscitated with isotonic crystalloids and norepinephrine for 4.25 h. Elamipretide-treated animals required less crystalloids than the controls (62.5 50-90 and 25 5-30 mL/kg, respectively), but similar amounts of norepinephrine (24.7 8.6-39.3 and 9.7 2.1-12.5 mcg/kg, respectively). Treatment animals had a significant reduction in serum creatinine (control: 2.7 2.6-2.8; Elamipretide: 2.4 2.4-2.5 mg/dL; p = 0.04), troponin (control: 3.20 2.14-5.47 ng/mL, Elamipretide: 0.22 0.1-1.91 ng/mL; p = 0.03), and interleukin-6 concentrations at the end of the study. There were no differences in final plasma lactate concentration. Elamipretide reduced fluid requirements and protected the kidney and heart after profound IRI. Further understanding the subcellular consequences of REBOA and mitochondrial rescue will open new therapeutic avenues for patients suffering from IRI after hemorrhage.
This paper reviews the biogeography of the Australian monsoon tropical biome to highlight general patterns in the distribution of a range of organisms and their environmental correlates and ...evolutionary history, as well as to identify knowledge gaps. Northern Australia, Australian Monsoon Tropics (AMT). The AMT is defined by areas that receive more than 85% of rainfall between November and April. Literature is summarized, including the origin of the monsoon climate, present-day environment, biota and habitat types, and phylogenetic and geographical relationships of selected organisms. Some species are widespread throughout the AMT while others are narrow-range endemics. Such contrasting distributions correspond to present-day climates, hydrologies (particularly floodplains), geological features (such as sandstone plateaux), fire regimes, and vegetation types (ranging from rain forest to savanna). Biogeographical and phylogenetic studies of terrestrial plants (e.g. eucalypts) and animals (vertebrates and invertebrates) suggest that distinct bioregions within the AMT reflect the aggregated effects of landscape and environmental history, although more research is required to determine and refine the boundaries of biogeographical zones within the AMT. Phylogenetic analyses of aquatic organisms (fishes and prawns) suggest histories of associations with drainage systems, dispersal barriers, links to New Guinea, and the existence of Lake Carpentaria, now submerged by the Gulf of Carpentaria. Complex adaptations to the landscape and climate in the AMT are illustrated by a number of species. The Australian monsoon is a component of a single global climate system, characterized by a dominant equator-spanning Hadley cell. Evidence of hot, seasonally moist climates dates back to the Late Eocene, implying that certain endemic elements of the AMT biota have a long history. Vicariant differentiation is inferred to have separated the Kimberley and Arnhem Land bioregions from Cape York Peninsula/northern Queensland. Such older patterns are overlaid by younger events, including dispersal from Southeast Asia, and range expansions and contractions. Future palaeoecological and phylogenetic investigations will illuminate the evolution of the AMT biome. Understanding the biogeography of the AMT is essential to provide a framework for ecological studies and the sustainable development of the region.
Almost 3000 men who received a placebo in the Prostate Cancer Prevention Trial and who never had a prostate-specific antigen (PSA) level of more than 4.0 ng per milliliter during the seven years of ...the trial underwent a prostate biopsy at the end of the study. Biopsy revealed prostate cancer in 449 men (15 percent), 67 of whom had high-grade tumors.
A PSA level of 4.0 ng per milliliter or less does not rule out the presence of prostate cancer, including high-grade tumors.
When first described in 1979, prostate-specific antigen (PSA) was considered a useful marker for assessing treatment responses and follow-up among patients with prostate cancer.
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After the publication of reports on several series in which the need for a biopsy of the prostate was based on the results of PSA tests, the potential of the PSA level as a screening tool was recognized.
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Further experience led to the consensus that a PSA level of more than 4.0 ng per milliliter had predictive value for the diagnosis of prostate cancer.
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Disease detection subsequently increased dramatically.
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More recent data suggest that a . . .
Abstract Adaptation is a central component of climate policy, helping manage and reduce risks. Sometimes, however, adaptation to climate change may consume energy, threatening efforts to reduce ...greenhouse gas emissions. Examples are numerous, and include the use of air conditioning or water desalination. Nevertheless, no clear view exists on how energy demand globally can be impacted by climate change. In this paper we systematically map existing evidence on how and to what extent adaptation responses to climate change may impact energy demand. The literature is large, fast-growing and spans several disciplines, but we identify several research gaps. First, the literature focuses almost exclusively on heating and cooling demand, while overlooking other potential sectors. It also focuses heavily on a few world regions, while local specific climate and socio-economic conditions may highly influence the impacts, and focuses largely on average demand, while often disregarding peak energy demand. Finally, and most importantly, only a handful of papers—most of them with a specific geographical scope—consider that different adaptation possibilities may lead to different impacts on energy demand, which is an important prerequisite if the impact of adaptation on energy demand is to be lowered and maladaptation to be avoided. The reviewed papers study for the most part similar options, and most adaptation possibilities are conversely studied by just one or two papers.
Background The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high-grade prostate cancer with finasteride ...compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects on tumor morphology or prostate size. Methods Prostate biopsies with Gleason score 8–10 (n = 90, finasteride; n = 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7–10 (n = 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided. Results Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm3, P<.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P = .016), mean tumor linear extent (greatest 4.4 versus 4.8 mm, P = .19 and aggregate 7.6 versus 9.2 mm, P = .13), bilaterality (22.8% versus 30.6%, P = .046), and perineural invasion (14.2% versus 20.3%, P = .07). Among patients who had prostatectomy, the finasteride-associated increase in high-grade disease (Gleason score ≥ 7) at biopsy (42.7% finasteride versus 25.4% placebo, P<.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P = .10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P = .01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups. Conclusions Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group.
First experimental observations in the Wendelstein 7-X stellarator indicate that the impurity confinement can be explained by turbulent processes. In particular, plasma discharges with increased ion ...to electron temperature ratio are accompanied by reduced electron density fluctuation amplitudes and anomalous impurity diffusion, suggesting a lower turbulent transport. Employing gyro-kinetic numerical simulations, we argue that the temperature ratio plays a key role for reducing the ion temperature gradient instability in Wendelstein 7-X, leading to an enhanced impurity confinement.
Context. The potentially hazardous asteroid (85990) 1999 JV6 has been a target of previously published thermal-infrared observations and optical photometry. It has been identified as a promising ...candidate for possible Yarkovsky-O’Keefe-Radzievskii-Paddack (YORP) effect detection. Aims. The YORP effect is a small thermal-radiation torque considered to be a key factor in spin-state evolution of small Solar System bodies. In order to detect YORP on 1999 JV6 we developed a detailed shape model and analysed the spin-state using both optical and radar observations. Methods. For 1999 JV6, we collected optical photometry between 2007 and 2016. Additionally, we obtained radar echo-power spectra and imaging observations with Arecibo and Goldstone planetary radar facilities in 2015, 2016, and 2017. We combined our data with published optical photometry to develop a robust physical model. Results. We determine that the rotation pole resides at negative latitudes in an area with a 5° radius close to the south ecliptic pole. The refined sidereal rotation period is 6.536787 ± 0.000007 h. The radar images are best reproduced with a bilobed shape model. Both lobes of 1999 JV6 can be represented as oblate ellipsoids with a smaller, more spherical component resting at the end of a larger, more elongated component. While contact binaries appear to be abundant in the near-Earth population, there are only a few published shape models for asteroids in this particular configuration. By combining the radar-derived shape model with optical light curves we determine a constant-period solution that fits all available data well. Using light-curve data alone we determine an upper limit for YORP of 8.5 × 10−8 rad day−2. Conclusions. The bifurcated shape of 1999 JV6 might be a result of two ellipsoidal components gently merging with each other, or a deformation of a rubble pile with a weak-tensile-strength core due to spin-up. The physical model of 1999 JV6 presented here will enable future studies of contact binary asteroid formation and evolution.
The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish ...between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.
Little is known about primary care physicians' (PCPs) prescribing of opioids. We describe trends and factors associated with opioid prescribing during PCP visits over the past decade. Using the ...National Ambulatory Medical Care Survey, we found an opioid prescribed in 2,206 (5%) PCP visits from 1992 to 2001. The prevalence of visits where an opioid was prescribed increased from a low of 41 per 1000 visits in 1992-1993 to a peak of 63 per 1000 in 1998-1999 (P < .0001 for trend) and then stabilized (59 per 1000 in 2000-2001). Several factors increased the odds of receiving an opioid: having Medicaid (odds ratio OR 2.09 95% confidence interval (CI) 1.82-2.40) or Medicare (OR 2.00 95% CI 1.68-2.39); having a visit between 15 and 35 minutes (OR 1.16 95% CI 1.05-1.27); and receiving an NSAID (OR 2.27 95% CI 2.04-2.53). Patients of hispanic (OR .67 95% CI .56-.81) or other race/ethnicity (OR .68 95% CI .52-.90), patients in health maintenance organizations (OR .74 95% CI .66-.84), and those living in the northeast (OR .60 95% CI .51-.69) or midwest (OR .75 95% CI .66-.85) had lower odds of receiving an opioid. Substantial variation exists in opioid prescribing by PCPs. Now that pain management standards are advocated, understanding the dynamics of opioid prescribing is necessary.
This study describes a decade-long increase in opioid prescribing by U.S. primary care physicians and identifies important geographic-, racial/ethnic-, and insurance-related differences in who receives these medications. Several underlying factors, including regulatory and legal pressures, attitudes and knowledge of opioids, and publicized opioid-related events, may contribute to these differences.
The cosmopolitan killer whale Orcinus orca feeds on a wide variety of prey types over its global range, but in at least some regions, genetically distinct and ecologically specialised lineages of ...killer whales coexist sympatrically. In coastal waters of the northeastern Pacific, 2 such lineages have been well described: the so-called 'residents' prey on teleost fish, especially salmonids and the other ('transients') on marine mammals. A third lineage in this region ('offshores') appears from chemical tracers to be ecologically distinct from residents and transients, but its diet is very poorly known. Here we describe 2 encounters with offshore killer whales during which multiple predation events involving sharks were observed. Using DNA analysis of tissue samples collected from these predation events, we identified the prey species as Pacific sleeper shark Somniosus pacificus and determined that a minimum of 16 individuals were consumed over the 2 encounters. This represents the first confirmed prey species of offshore killer whales based on field observations of foraging and the first record of any Somniosus species in the prey of Orcinus. We also show quantitatively that apical tooth wear is far greater in offshores than in resident and transient killer whales, and propose that such wear is at least in part due to abrasion from dermal denticles embedded in shark skin. Further studies are needed to determine whether offshore killer whales are as specialised ecologically as resident and transient killer whales, and whether sharks play a dominant role in their diet.
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