1,639 research outputs found
Global academic response to COVID â19: Crossâsectional study
This study explores the response to COVIDâ19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A crossâsectional bibliometric review of COVIDâ19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submissionâtoâacceptance time and availability of original data. Publisherâresponsiveness was assessed by measuring the acceptanceâtoâpublication time and the provision of open access. Three hundred and ninetyâeight of 2,835 COVIDâ19 and 55 of 1,513 MERS search results were eligible. Most COVIDâ19 studies were clinical reports (n =â242; 60.8%). The submissionâtoâacceptance [median: 5âdays (IQR: 3â11) versus 71.5âdays (38â106); P <â.001] and acceptanceâtoâpublication [median: 5âdays (IQR: 2â8) versus 22.5âdays (4â48¡5â; P <â.001] times were strikingly shorter for COVIDâ19. Almost all COVIDâ19 (n =â396; 99.5%) and MERS (n =â55; 100%) studies were openâaccess. Data sharing was infrequent, with original data available for 104 (26.1%) COVIDâ19 and 10 (18.2%) MERS studies (P =â.203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only oneâinâfour were published alongside original data, which is a key target for improvement
Target of Rapamycin Inhibitors (TOR-I; Sirolimus and Everolimus) for Primary Immunosuppression in Kidney Transplant Recipients
Background: Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are immunosuppressive agents with a novel mode of action but an uncertain clinical role. Objectives: To investigate the benefits and harms of immunosuppressive regimens containing TOR-I when compared to other regimens as initial therapy for kidney transplant recipients. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library, issue 2, 2005), MEDLINE (1966-June 2005), EMBASE (1980-June 2005), the specialised register of the Cochrane Renal Group (June 2005)., and contacted authors and pharmaceutical companies to identify relevant studies. Selection criteria: All randomised controlled trials (RCTs) and quasi-RCTs where drug regimens containing TOR-I were compared to alternative drug regimens in the immediate post-transplant period were included, without age restriction, dosage or language of report. Data collection and analysis: Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as relative risk (RR) or weight mean difference (MD) with 95% confidence intervals (CI). Main results: Thirty three trials (142 reports) were included (sirolimus (27), everolimus (5), head-to-head (1)). When TOR-I replaced CNI there was no difference in acute rejection, but serum creatinine was lower (MD -18.31 micromol/L, -30.96 to -5.67), and bone marrow more suppressed (leucopenia: RR 2.02 1.12 to 3.66; thrombocytopenia: RR 6.97 2.97 to 16.36; anaemia: RR 1.67, 1.27 to 2.20). When TOR-I replaced antimetabolites, acute rejection (RR 0.84, 0.71 to 0.99) and cytomegalovirus infection (CMV) (RR 0.49; 0.37 to 0.65) were reduced, but hypercholesterolaemia was increased (RR 1.65, 1.32 to 2.06). For low versus high-dose TOR-I, with equal CNI dose, rejection was increased (RR 1.23, 1.06 to 1.43) but calculated GFR higher (MD 4.27 mL/min, 1.12 to 7.41), and for low-dose TOR-I/standard-dose CNI versus higher-dose TOR-I/reduced CNI, acute rejection (RR 0.67, 0.52 to 0.88) and calculated GFR (MD -9.46 mL/min, -12.16 to -6.76) were reduced. There was no significant difference in mortality, graft loss or malignancy risk for TOR-I in any comparison. Authors' conclusions: TOR-I have been evaluated in four different primary immunosuppressive algorithms; as replacement for CNI and for antimetabolites, in combination with CNI at low and high dose and with variable dose of CNI. Generally, surrogate endpoints for graft survival favour TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes are worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust RCTs are still needed
Epigenetic Differences in Cortical Neurons from a Pair of Monozygotic Twins Discordant for Alzheimer's Disease
DNA methylation [1], [2] is capable of modulating coordinate expression of large numbers of genes across many different pathways, and may therefore warrant investigation for their potential role between genes and disease phenotype. In a rare set of monozygotic twins discordant for Alzheimer's disease (AD), significantly reduced levels of DNA methylation were observed in temporal neocortex neuronal nuclei of the AD twin. These findings are consistent with the hypothesis that epigenetic mechanisms may mediate at the molecular level the effects of life events on AD risk, and provide, for the first time, a potential explanation for AD discordance despite genetic similarities
Target of rapamycin inhibitors (TORâI; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients
Background Kidney transplantation is the therapy of choice for many patients with endâstage kidney disease (ESKD) with an improvement in survival rates and satisfactory short term graft survival. However, there has been little improvement in longâterm survival. The place of target of rapamycin inhibitors (TORâI) (sirolimus, everolimus), which have different modes of action from other commonly used immunosuppressive agents, in kidney transplantation remains uncertain. This is an update of a review first published in 2006. Objectives To evaluate the short and longâterm benefits and harms of TORâI (sirolimus and everolimus) when used in primary immunosuppressive regimens for kidney transplant recipients. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 20 September 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria All randomised controlled trials (RCTs) and quasiâRCTs in which drug regimens, containing TORâI commenced within seven days of transplant, were compared to alternative drug regimens, were included without age restriction, dosage or language of report. Data collection and analysis Three authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the randomâeffects model. The certainty of the evidence was assessed using GRADE Main results Seventy studies (17,462 randomised participants) were included; eight studies included two comparisons to provide 78 comparisons. Outcomes were reported at six months to three years post transplant. Risk of bias was judged to be low for sequence generation in 25 studies, for allocation concealment in 23 studies, performance bias in four studies, detection bias in 65 studies, attrition bias in 45 studies, selective reporting bias in 48 studies, and for other potential bias in three studies. Risk of bias was judged to be at high risk of bias for sequence generation in two studies, allocation concealment in two studies, performance bias in 61 studies, detection bias in one study, attrition bias in four studies, for selective reporting bias in 11 studies and for other potential risk of bias in 46 studies. Compared with CNI and antimetabolite, TORâI with antimetabolite probably makes little or no difference to death (RR 1.31, 95% CI 0.87 to 1.98; 19 studies) or malignancies (RR 0.86, 95% CI 0.50 to 1.48; 10 studies); probably increases graft loss censored for death (RR 1.32, 95% CI 0.96 to 1.81; 15 studies), biopsyâproven acute rejection (RR 1.60, 95% CI 1.25 to 2.04; 15 studies), need to change treatment (RR 2.42, 95% CI 1.88 to 3.11; 14 studies) and wound complications (RR 2.56, 95% CI 1.94 to 3.36; 12 studies) (moderate certainty evidence); but reduces CMV infection (RR 0.43, 95% CI 0.29 to 0.63; 13 studies) (high certainty evidence). Compared with antimetabolites and CNI, TORâI with CNI probably makes little or no difference to death (RR 1.06, 95% CI 0.84 to 1.33; 31 studies), graft loss censored for death (RR 1.09, 95% CI 0.82 to 1.45; 26 studies), biopsyâproven acute rejection (RR 0.95, 95% CI 0.81 to 1.12; 24 studies); and malignancies (RR 0.83, 95% CI 0.64 to 1.07; 17 studies); probably increases the need to change treatment (RR 1.56, 95% CI 1.28 to 1.90; 25 studies), and wound complications (RR 1.56, 95% CI 1.28 to 1.91; 17 studies); but probably reduces CMV infection (RR 0.44, 95% CI 0.34 to 0.58; 25 studies) (moderate certainty evidence). Lower dose TORâI and standard dose CNI compared with higher dose TORâI and reduced dose CNI probably makes little or no difference to death (RR 1.07, 95% CI 0.64 to 1.78; 9 studies), graft loss censored for death (RR 1.09, 95% CI 0.54 to 2.20; 8 studies), biopsyâproven acute rejection (RR 0.87, 95% CI 0.67 to 1.13; 8 studies), and CMV infection (RR 1.42, 95% CI 0.78 to 2.60; 5 studies) (moderate certainty evidence); and may make little or no difference to wound complications (RR 0.95, 95% CI 0.53 to 1.71; 3 studies), malignancies (RR 1.04, 95% CI 0.36 to 3.04; 7 studies), and the need to change treatments (RR 1.18, 95% CI 0.58 to 2.42; 5 studies) (low certainty evidence). Lower dose of TORâI compared with higher doses probably makes little or no difference to death (RR 0.84, 95% CI 0.67 to 1.06; 13 studies), graft loss censored for death (RR 0.92, 95% CI 0.71 to 1.19; 12 studies), biopsyâproven acute rejection (RR 1.26, 95% CI 1.10 to 1.43; 11 studies), CMV infection (RR 0.87, 95% CI 0.63 to 1.21; 9 studies), wound complications (RR 0.92, 95% CI 0.66 to 1.29; 7 studies), and malignancy (RR 0.84, 95% CI 0.54 to 1.32; 10 studies) (moderate certainty evidence); and may make little or no difference to the need to change treatments (RR 0.91, 95% CI 0.78 to 1.05; 10 studies) (low certainty evidence). It is uncertain whether sirolimus and everolimus differ in their effects on kidney function and lipid levels because the certainty of the evidence is very low based on a single small study with only three months of followâup. Authors' conclusions In studies with followâup to three years, TORâI with an antimetabolite increases the risk of graft loss and acute rejection compared with CNI and an antimetabolite. TORâI with CNI potentially offers an alternative to an antimetabolite with CNI as rates of graft loss and acute rejection are similar between interventions and TORâI regimens are associated with a reduced risk of CMV infections. Wound complications and the need to change immunosuppressive medications are higher with TORâI regimens. While further new studies are not required, longerâterm followâup data from participants in existing methodologically robust RCTs are needed to determine how useful immunosuppressive regimens, which include TORâI, are in maintaining kidney transplant function and survival beyond three years
Umbilical hernia rupture with evisceration of omentum from massive ascites: a case report
<p>Abstract</p> <p>Introduction</p> <p>The incidence of hernias is increased in patients with alcoholic liver disease with ascites. To the best of our knowledge, this is the first report of an acute rise in intra-abdominal pressure from straining for stool as the cause of a ruptured umbilical hernia.</p> <p>Case presentation</p> <p>An 81-year-old Caucasian man with a history of alcoholic liver disease presented to our emergency department with an erythematous umbilical hernia and clear, yellow discharge from the umbilicus. On straining for stool, after initial clinical assessment, our patient noted a gush of fluid and evisceration of omentum from the umbilical hernia. An urgent laparotomy was performed with excision of the umbilicus and devitalized omentum.</p> <p>Conclusion</p> <p>We report the case of a patient with a history of alcoholic liver disease with ascites. Ascites causes a chronic increase in intra-abdominal pressure. A sudden increase in intra-abdominal pressure, such as coughing, vomiting, gastroscopy or, as in this case, straining for stool can cause rupture of an umbilical hernia. The presence of discoloration, ulceration or a rapid increase in size of the umbilical hernia signals impending rupture and should prompt the physician to reduce the intra-abdominal pressure.</p
Dusty Planetary Systems
Extensive photometric stellar surveys show that many main sequence stars show
emission at infrared and longer wavelengths that is in excess of the stellar
photosphere; this emission is thought to arise from circumstellar dust. The
presence of dust disks is confirmed by spatially resolved imaging at infrared
to millimeter wavelengths (tracing the dust thermal emission), and at optical
to near infrared wavelengths (tracing the dust scattered light). Because the
expected lifetime of these dust particles is much shorter than the age of the
stars (>10 Myr), it is inferred that this solid material not primordial, i.e.
the remaining from the placental cloud of gas and dust where the star was born,
but instead is replenished by dust-producing planetesimals. These planetesimals
are analogous to the asteroids, comets and Kuiper Belt objects (KBOs) in our
Solar system that produce the interplanetary dust that gives rise to the
zodiacal light (tracing the inner component of the Solar system debris disk).
The presence of these "debris disks" around stars with a wide range of masses,
luminosities, and metallicities, with and without binary companions, is
evidence that planetesimal formation is a robust process that can take place
under a wide range of conditions. This chapter is divided in two parts. Part I
discusses how the study of the Solar system debris disk and the study of debris
disks around other stars can help us learn about the formation, evolution and
diversity of planetary systems by shedding light on the frequency and timing of
planetesimal formation, the location and physical properties of the
planetesimals, the presence of long-period planets, and the dynamical and
collisional evolution of the system. Part II reviews the physical processes
that affect dust particles in the gas-free environment of a debris disk and
their effect on the dust particle size and spatial distribution.Comment: 68 pages, 25 figures. To be published in "Solar and Planetary
Systems" (P. Kalas and L. French, Eds.), Volume 3 of the series "Planets,
Stars and Stellar Systems" (T.D. Oswalt, Editor-in-chief), Springer 201
High sample throughput genotyping for estimating C-lineage introgression in the dark honeybee: an accurate and cost-effective SNP-based tool
The natural distribution of the honeybee (Apis mellifera L.) has been changed by humans in recent
decades to such an extent that the formerly widest-spread European subspecies, Apis mellifera
mellifera, is threatened by extinction through introgression from highly divergent commercial strains
in large tracts of its range. Conservation efforts for A. m. mellifera are underway in multiple European
countries requiring reliable and cost-efficient molecular tools to identify purebred colonies. Here, we
developed four ancestry-informative SNP assays for high sample throughput genotyping using the
iPLEX Mass Array system. Our customized assays were tested on DNA from individual and pooled,
haploid and diploid honeybee samples extracted from different tissues using a diverse range of
protocols. The assays had a high genotyping success rate and yielded accurate genotypes. Performance
assessed against whole-genome data showed that individual assays behaved well, although the
most accurate introgression estimates were obtained for the four assays combined (117 SNPs).
The best compromise between accuracy and genotyping costs was achieved when combining two
assays (62 SNPs). We provide a ready-to-use cost-effective tool for accurate molecular identification
and estimation oinfo:eu-repo/semantics/publishedVersio
Does familial risk for alcohol use disorder predict alcohol hangover?
Positive family history of alcohol use disorder (FHP), a variable associated with propensity for alcohol use disorder (AUD), has been linked with elevated hangover frequency and severity, after controlling for alcohol use. This implies that hangover experiences may be related to AUD. However, inadequate control of alcohol consumption levels, low alcohol dose and testing for hangover during the intoxication phase detract from these findings. Here, we present further data pertinent to understanding the relationship between family history and alcohol hangover. Study 1 compared past year hangover frequency in a survey of 24 FHP and 118 family history negative (FHN) individuals. Study 2 applied a quasi-experimental naturalistic approach assessing concurrent hangover severity in 17 FHP and 32 FHN individuals the morning after drinking alcohol. Both studies applied statistical control for alcohol consumption levels. In Study 1, both FHP status and estimated blood alcohol concentration on the heaviest drinking evening of the past month predicted the frequency of hangover symptoms experienced over the previous 12Â months. In Study 2, estimated blood alcohol concentration the previous evening predicted hangover severity but FHP status did not. FHP, indicating familial risk for AUD, was not associated with concurrent hangover severity but was associated with increased estimates of hangover frequency the previous year
The Global Research Neglect of Unassisted Smoking Cessation: Causes and Consequences
Simon Chapman and Ross MacKenzie review the evidence and argue that health promotion messages should emphasize that the most successful method used by most ex-smokers is unassisted cessation
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