141 research outputs found
Peripheral arterial disease: gadolinium-enhanced MR angiography versus color-guided duplex US--a meta-analysis
PURPOSE: To summarize and compare the published data on
gadolinium-enhanced magnetic resonance (MR) angiography and color-guided
duplex ultrasonography (US) for the work-up for peripheral arterial
disease. MATERIALS AND METHODS: Studies published between January 1984 and
November 1998 were included if (a) gadolinium-enhanced MR angiography
and/or color-guided duplex US were performed for evaluation of arterial
stenoses and occlusions in the work-up for peripheral arterial disease of
the lower extremities, (b) conventional angiography was the reference
standard, and (c) absolute numbers of true-positive, false-negative,
true-negative, and false-positive results were available or derivable.
RESULTS: With a random effects model, pooled sensitivity for MR
angiography (97.5% [95% CI: 95.7%, 99.3%]) was higher than that for duplex
US (87.6% [95% CI: 84.4%, 90.8%]). Pooled specificities were similar:
96.2% (95% CI: 94.4%, 97.9%) for MR angiography and 94.7% (95% CI: 93.2%,
96.2%) for duplex US. Summary receiver operating characteristic analysis
demonstrated better discriminatory power for MR angiography than for
duplex US. Regression coefficients for MR angiography versus US were 1.67
(95% CI: -0.23, 3.56) with adjustment for covariates, 2.11 (95% CI: 0.12,
4.09) without such adjustment, and 1.73 (95% CI: 0.44, 3.02) with a random
effects model. CONCLUSION: Gadolinium-enhanced MR angiography has better
discriminatory power than does color-guided duplex US and is a highly
sensitive and specific method, as compared with conventional angiography,
for the work-up for peripheral arterial disease
The prevalence and incidence of musculoskeletal symptoms among hospital physicians: a systematic review
Physicians are exposed to a range of work-related risk factors that may result in occupational diseases. This systematic review aims at shedding light on the prevalence and incidence of musculoskeletal complaints among hospital physicians. A systematic literature search was performed in Pubmed and EMBASE (1990-2010), and methodological quality criteria were applied. A search was done for musculoskeletal complaints. Five medium-quality studies and three high-quality studies were included in this review. The definitions and assessment used in the studies for musculoskeletal complaints were different. In short, the frequently reported prevalence for hand and wrist pain was 8-33 and 0%, 17% for shoulder pain, and 9-28% for neck pain. Moreover, the annual prevalence of low back pain was between 33 and 68%. The limited number of studies makes it difficult to draw conclusions, and the results should be intepreted with care. In conclusion, musculoskeletal complaints may be work-related complaints in hospital physicians, which need future attentio
Living renal donors: optimizing the imaging strategy--decision- and cost-effectiveness analysis
PURPOSE: To determine the most cost-effective strategy for preoperative
imaging performed in potential living renal donors. MATERIALS AND METHODS:
In a decision-analytic model, the societal cost-effectiveness of digital
subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR)
angiography, contrast material-enhanced spiral computed tomographic (CT)
angiography, and combinations of these imaging techniques was evaluated.
Outcome measures included lifetime cost, quality-adjusted life-years
(QALYs), and incremental cost-effectiveness ratios. A base-case analysis
was performed with a 40-year-old female donor and a 40-year-old female
recipient. RESULTS: For the donor, MR angiography (24.05 QALYs and 9,000
dollars) dominated all strategies except for MR angiography with CT
angiography, which had an incremental ratio of 245,000 dollars per QALY.
For the recipient, DSA and DSA with MR angiography yielded similar results
(10.46 QALYs and 179,000 dollars) and dominated all other strategies. When
results for donor and recipient were combined, DSA dominated all other
strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a
99% specificity or less for detection of renal disease, MR angiography
with CT angiography was superior (34.47 QALYs and 190,000 dollars).
CONCLUSION: For preoperative imaging in a potential renal donor, DSA is
the most cost-effective strategy if it has a specificity greater than 99%
for detection of renal disease; otherwise, MR angiography with CT
angiography is the most cost-effective strategy
RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2
Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting RAD51 nucleofilament formation at stalled replication forks. CDK2 phosphorylates BRCA2 (pS3291-BRCA2) to limit stabilizing contacts with polymerized RAD51; however, how replication stress modulates CDK2 activity and whether loss of pS3291-BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that LATS1 forms part of an ATR-mediated response to replication stress that requires the tumour suppressor RASSF1A. Importantly, perturbation of the ATR–RASSF1A–LATS1 signalling axis leads to genomic defects associated with loss of BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers
Missed treatment opportunities and barriers to comprehensive treatment for sexual violence survivors in Kenya: a mixed methods study
Background
In Kenya, most sexual violence survivors either do not access healthcare, access healthcare late or do not complete treatment. To design interventions that ensure optimal healthcare for survivors, it is important to understand the characteristics of those who do and do not access healthcare. In this paper, we aim to: compare the characteristics of survivors who present for healthcare to those of survivors reporting violence on national surveys; understand the healthcare services provided to survivors; and, identify barriers to treatment.
Methods
A mixed methods approach was used. Hospital records for survivors from two referral hospitals were compared with national-level data from the Kenya Demographic and Health Survey 2014, and the Violence Against Children Survey 2010. Descriptive summaries were calculated and differences in characteristics of the survivors assessed using chi-square tests. Qualitative data from six in-depth interviews with healthcare providers were analysed thematically.
Results
Among the 543 hospital respondents, 93.2% were female; 69.5% single; 71.9% knew the perpetrator; and 69.2% were children below 18 years. Compared to respondents disclosing sexual violence in nationally representative datasets, those who presented at hospital were less likely to be partnered, male, or assaulted by an intimate partner. Data suggest missed opportunities for treatment among those who did present to hospital: HIV PEP and other STI prophylaxis was not given to 30 and 16% of survivors respectively; 43% of eligible women did not receive emergency contraceptive; and, laboratory results were missing in more than 40% of the records. Those aged 18 years or below and those assaulted by known perpetrators were more likely to miss being put on HIV PEP. Qualitative data highlighted challenges in accessing and providing healthcare that included stigma, lack of staff training, missing equipment and poor coordination of services.
Conclusions
Nationally, survivors at higher risk of not accessing healthcare include older survivors; partnered or ever partnered survivors; survivors experiencing sexual violence from intimate partners; children experiencing violence in schools; and men. Interventions at the community level should target survivors who are unlikely to access healthcare and address barriers to early access to care. Staff training and specific clinical guidelines/protocols for treating children are urgently needed
Testing Biochemistry Revisited: How In Vivo Metabolism Can Be Understood from In Vitro Enzyme Kinetics
A decade ago, a team of biochemists including two of us, modeled yeast glycolysis and showed that one of the most studied biochemical pathways could not be quite understood in terms of the kinetic properties of the constituent enzymes as measured in cell extract. Moreover, when the same model was later applied to different experimental steady-state conditions, it often exhibited unrestrained metabolite accumulation
The Evolution of Fangs, Venom, and Mimicry Systems in Blenny Fishes
Venom systems have evolved on multiple occasions
across the animal kingdom, and they can act as key
adaptations to protect animals from predators.
Consequently, venomous animals serve as models
for a rich source of mimicry types, as non-venomous
species benefit from reductions in predation risk by
mimicking the coloration, body shape, and/or movement
of toxic counterparts. The frequent evolution
of such deceitful imitations provides notable
examples of phenotypic convergence and are often
invoked as classic exemplars of evolution by natural
selection. Here, we investigate the evolution of fangs,
venom, and mimetic relationships in reef fishes from
the tribe Nemophini (fangblennies). Comparative
morphological analyses reveal that enlarged canine
teeth (fangs) originated at the base of the Nemophini
radiation and have enabled a micropredatory feeding
strategy in non-venomous Plagiotremus spp. Subsequently,
the evolution of deep anterior grooves and
their coupling to venom secretory tissue provide
Meiacanthus spp. with toxic venom that they effectively
employ for defense. We find that fangblenny
venom contains a number of toxic components that
have been independently recruited into other animal
venoms, some of which cause toxicity via interactions
with opioid receptors, and result in a multifunctional
biochemical phenotype that exerts potent hypotensive
effects. The evolution of fangblenny venom has
seemingly led to phenotypic convergence via the formation
of a diverse array of mimetic relationships that
provide protective (Batesian mimicry) and predatory
(aggressive mimicry) benefits to other fishes.
Our results further our understanding of how novel
morphological and biochemical adaptations stimulate
ecological interactions in the natural world
Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids
BACKGROUND
Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown.
OBJECTIVES
To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change.
METHODS
Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses.
RESULTS
For the included 389 patients (55% female; mean body mass index, 28 ± 5 kg/m; 58% maintenance OCS), mean weight decreased -0.27 kg/y (95% CI, -0.51 to -0.03; P = .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI, -1.21 to -0.52; P < .001] vs +0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (β = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (β = 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001).
CONCLUSIONS
Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired
Towards a New Paradigm of Non-Captive Research on Cetacean Cognition
Contemporary knowledge of impressive neurophysiology and behavior in cetaceans, combined with increasing opportunities for studying free-ranging cetaceans who initiate sociable interaction with humans, are converging to highlight serious ethical considerations and emerging opportunities for a new era of progressive and less-invasive cetacean research. Most research on cetacean cognition has taken place in controlled captive settings, e.g., research labs, marine parks. While these environments afford a certain amount of experimental rigor and logistical control they are fraught with limitations in external validity, impose tremendous stress on the part of the captive animals, and place burdens on populations from which they are often captured. Alternatively, over the past three decades, some researchers have sought to focus their attention on the presence of free-ranging cetacean individuals and groups who have initiated, or chosen to participate in, sociable interactions with humans in the wild. This new approach, defined as Interspecies Collaborative Research between cetacean and human, involves developing novel ways to address research questions under natural conditions and respecting the individual cetacean's autonomy. It also offers a range of potential direct benefits to the cetaceans studied, as well as allowing for unprecedented cognitive and psychological research on sociable mysticetes. Yet stringent precautions are warranted so as to not increase their vulnerability to human activities or pathogens. When conducted in its best and most responsible form, collaborative research with free-ranging cetaceans can deliver methodological innovation and invaluable new insights while not necessitating the ethical and scientific compromises that characterize research in captivity. Further, it is representative of a new epoch in science in which research is designed so that the participating cetaceans are the direct recipients of the benefits
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