Thermal performance curves (TPCs), which quantify how an ectotherm's body temperature (Tb) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate ...change. Here, we examine the key – but often biologically unreasonable – assumptions underlying this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced Tb. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs. For example, rather than assuming that TPCs are fixed during ontogeny, one can measure TPCs for each major life stage and incorporate these into stage‐specific ecological models to reveal the life stage most likely to be vulnerable to climate change. Our overall goal is to explicitly examine the assumptions underlying the integration of TPCs with Tb, to develop a framework within which empiricists can place their work within these limitations, and to facilitate the application of thermal physiology to understanding the biological implications of climate change.
Abstract Background The oncologic equivalence of laparoscopic distal pancreatectomy (LDP) to open pancreatectomy (ODP) for ductal adenocarcinoma (DAC) is not established. Methods The National Cancer ...Data Base was used to compare perioperative outcomes following LDP and ODP for DAC between 2010 and 2011. Results One hundred forty-five patients underwent LDP; 625 underwent ODP. Compared with ODP, patients undergoing LDP were older (68 ± 10.1 vs 66 ± 10.5 years, P = .027), more likely treated in academic centers (70% vs 59%, P = .01), and had shorter hospital stays (6.8 ± 4.6 vs 8.9 ± 7.5 days, P < .001). Demographic data, lymph node count, 30-day unplanned readmission, and 30-day mortality were identical between groups. Multivariable regression identified a lower probability of prolonged length of stay with LDP (odds ratio .51, 95% confidence interval .327 to .785, P = .0023). There was no association between surgical approach and node count, readmission, or mortality. Conclusion LDP for DAC provides shorter postoperative lengths of stay and rates of readmission and 30-day mortality similar to OPD without compromising perioperative oncologic outcomes.
Background There is considerable debate about the safety and clinical equivalence of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for pancreatic ductal ...adenocarcinoma (PDCA). Study Design We queried the National Cancer Data Base to identify patients undergoing LPD and OPD for PDCA between 2010 and 2011. Chi-square and Student's t -tests were used to evaluate differences between the 2 approaches. Multivariable logistic regression modeling was performed to identify patient, tumor, or facility factors associated with perioperative mortality. Results Four thousand and thirty-seven (91%) patients underwent OPD. Three hundred and eighty-four (9%) patients underwent LPD. There were no statistical differences between the 2 surgical cohorts with regard to age, race, Charlson score, tumor size, grade, stage, or treatment with neoadjuvant chemoradiotherapy. Laparoscopic pancreaticoduodenectomy demonstrated a shorter length of stay (10 ± 8 days vs 12 ± 9.7 days; p < 0.0001) and lower rates of unplanned readmission (5% vs 9%; p = 0.027) than OPD. In an unadjusted comparison, there was no difference in 30-day mortality between the LPD and OPD cohorts (5.2% vs 3.7%; p = 0.163). Multivariable logistic regression modeling predicting perioperative mortality controlling for age, Charlson score, tumor size, nodal positivity, stage, facility type, and pancreaticoduodenectomy volume identified age (odds ratio OR = 1.05; p < 0.0001), positive margins (OR = 1.45; p = 0.030), and LPD (OR = 1.89; p = 0.009) as associated with an increased probability of 30-day mortality; higher hospital volume was associated with a lower risk of 30-day mortality (OR = 0.98; p < 0.0001). In institutions that performed ≥10 LPDs, the 30-day mortality rate of the laparoscopic approach was equal to that for the open approach (0.0% vs 0.7%; p = 1.00). Conclusions Laparoscopic pancreaticoduodenectomy is equivalent to OPD in length of stay, margin-positive resection, lymph node count, and readmission rate. There is a higher 30-day mortality rate with LPD, but this appears driven by a surmountable learning curve for the procedure.
Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual ...patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.
Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 86% of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, 95% CI -4.9, -1.6 mmHg). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg -3.3, 1.2), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg -2.2, 1.8; ambulatory 1.1 mmHg -0.3, 2.5). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies.
Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rejecting theorizations of refugee camps as humanitarian spaces of exception and bare life, recent research has emphasized how camps are sites of material struggle, and how refugees are agential ...political subjects. While valuable, this research bifurcates between the material dwellings of refugee camps on one hand and the political subjectivity of refugees on the other. In contrast, this paper examines how Palestinian refugees reproduce a sense of collective belonging within the physical space of the camp and through material practices of care. This research centers the voices of Palestinian children to understand how they view their inherited refugee identities in the context of multi-generational displacement. Using participatory digital storytelling, this research illustrates how, for some Palestinian refugee children, a sense of longing for a future return to their past homeland motivates acts of care in the present that produces a sense of belonging in the camp. The creative agency that refugee youth demonstrate in articulating this entangled temporality of belonging challenges top-down models of youth socialization and refugee subjectivity. The importance of visual and narrative practices in reproducing refugee-ness suggests a wider role for creative methods in research with refugees. This paper introduces place-based digital storytelling as one such method.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Tumor suppressor gene TUSC2/FUS1 (TUSC2) is frequently inactivated early in lung cancer development. TUSC2 mediates apoptosis in cancer cells but not normal cells by upregulation of the intrinsic ...apoptotic pathway. No drug strategies currently exist targeting loss-of-function genetic abnormalities. We report the first in-human systemic gene therapy clinical trial of tumor suppressor gene TUSC2.
Patients with recurrent and/or metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous N-1-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTAP):cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2) every 3 weeks.
Thirty-one patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram). The MTD was determined to be 0.06 mg/kg. Five patients achieved stable disease (2.6-10.8 months, including 2 minor responses). One patient had a metabolic response on positron emission tomography (PET) imaging. RT-PCR analysis detected TUSC2 plasmid expression in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens and peripheral blood lymphocyte controls. Proximity ligation assay, performed on paired biopsies from 3 patients, demonstrated low background TUSC2 protein staining in pretreatment tissues compared with intense (10-25 fold increase) TUSC2 protein staining in post-treatment tissues. RT-PCR gene expression profiling analysis of apoptotic pathway genes in two patients with high post-treatment levels of TUSC2 mRNA and protein showed significant post-treatment changes in the intrinsic apoptotic pathway. Twenty-nine genes of the 82 tested in the apoptosis array were identified by Igenuity Pathway Analysis to be significantly altered post-treatment in both patients (Pearson correlation coefficient 0.519; p<0.01).
DOTAP:chol-TUSC2 can be safely administered intravenously in lung cancer patients and results in uptake of the gene by human primary and metastatic tumors, transgene and gene product expression, specific alterations in TUSC2-regulated pathways, and anti-tumor effects (to our knowledge for the first time for systemic DOTAP:cholesterol nanoparticle gene therapy).
ClinicalTrials.gov NCT00059605.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effects of progressive global acidification on the shells of marine organisms is a topic of much current interest. Most studies on molluscan shell resistance to dissolution consider the carbonate ...mineral component, with less known about the protective role of the outer organic periostracum. Outer-shell resistance would seem especially important to gastropods living in carbonate-undersaturated and calcium-deficient estuarine waters that threaten shell dissolution and constrain CaCO3 production. We tested this prediction using gastropods from an acidified estuarine population (Neripteron violaceum) that form a clay shield outside the periostracum. Specifically, we aimed to show that the carbonate shell component lacks integrity, that the formation of the clay shield is directed by the organism, and that the clay shield functions to protect against shell dissolution. We found no evidence for any specific carbonate dissolution resistance strategy in the thin, predominantly aragonitic shells of these gastropods. Shield formation was directed by an ornamented periostracum which strongly bonded illite elements (e.g., Fe, Al and S), that become available through suspension in the water column. In unshielded individuals, CaCO3 erosion was initiated randomly across the shell (not age-related) and progressed rapidly when the periostracum was breached. A light reflectance technique showed qualitatively that shield consolidation is negatively-related to shell erosion. These findings support a conceptual framework for gastropod outer-shell responses to acidification that considers both environmental and evolutionary constraints on shell construction. We describe a novel strategy for shell protection against dissolution, highlighting the diversity of mechanisms available to gastropods facing extreme coastal acidification.
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•Acidified estuaries compromise building and threaten dissolution of gastropods shells.•Periostracum of Neripteron snails directs formation of an outer shell clay shield.•Shield constructed of the mineral illite is tightly chemically-bonded to the periostracum.•The more reflective unshielded shells showed a greater rate of dissolution.•Ecological and evolutionary constraints on carbonate shell building predict outer protection.
We investigate the impact that the four principal large‐scale patterns of Southern Hemisphere (SH) atmospheric circulation variability have on Antarctic surface air temperature (SAT): (1) the ...southern baroclinic annular mode (BAM), which is associated with variations in extratropical storm amplitude; (2) the Southern Annular Mode (SAM), associated with latitudinal shifts in the midlatitude jet; and (3) the two Pacific‐South American patterns (PSA1 and PSA2), which are characterized by wave trains originating in the tropical Pacific that extend across the SH extratropics. A key aspect is the use of 35 years of daily observations and reanalysis data, which affords a sufficiently large sample size to assess the signatures of the circulation patterns in both the mean and variability of daily mean SAT anomalies. The BAM exerts the weakest influence on Antarctic SAT, albeit it is still important over select regions. Consistent with previous studies, the SAM is shown to influence SAT across most of the continent throughout the year. The PSA1 also affects SAT across almost all of Antarctica. Regionally, both PSA patterns can exert a greater impact on SAT than the SAM but also have a significantly weaker influence during summer, reflecting the seasonality of the SH response to El Niño–Southern Oscillation. The SAM and PSA patterns have distinct signatures in daily SAT variance that are physically consistent with their signatures in extratropical dynamic variability. The broad‐scale climate linkages identified here provide benchmarks for interpreting the Antarctic climate response to future changes in tropical sea surface temperatures, ozone recovery, and greenhouse gas increases.
Key Points
Large‐scale circulation patterns exert significant influence on Antarctic surface temperatures
The impact of the Pacific‐South American patterns is as large as the Southern Annular Mode
The circulation patterns also affect daily temperature variability across much of Antarctica
A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron ...transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning β-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment.
Mass bleaching associated with unusually high sea temperatures represents one of the greatest threats to corals and coral reef ecosystems. Deeper reef areas are hypothesized as potential refugia, but ...the susceptibility of Scleractinian species over depth has not been quantified. During the most severe bleaching event on record, we found up to 83% of coral cover severely affected on Maldivian reefs at a depth of 3–5 m, but significantly reduced effects at 24–30 m. Analysis of 153 species' responses showed depth, shading and species identity had strong, significant effects on susceptibility. Overall, 73.3% of the shallow-reef assemblage had individuals at a depth of 24–30 m with reduced effects, potentially mitigating local extinction and providing a source of recruits for population recovery. Although susceptibility was phylogenetically constrained, species-level effects caused most lineages to contain some partially resistant species. Many genera showed wide variation between species, including Acropora, previously considered highly susceptible. Extinction risk estimates showed species and lineages of concern and those likely to dominate following repeated events. Our results show that deeper reef areas provide refuge for a large proportion of Scleractinian species during severe bleaching events and that the deepest occurring individuals of each population have the greatest potential to survive and drive reef recovery.