69 research outputs found
INTOX - A PROSPECTIVE MEASUREMENT OF BLOOD CONCENTRATIONS OF ROUTINE DRUGS IN PATIENTS TREATED IN THE INTENSIVE CARE UNIT
Sense of entitlement to support for the reconciliation of employment and family life
This article explores young European women and men’s expectations of support - from the state and employers - for reconciling paid employment and family life. It is based on a qualitative study employing focus groups with young women and men in Norway, Sweden, Portugal, Ireland and the UK. Drawing on the concept of sense of entitlement, derived from social justice theory, it was expected that the type of welfare state and ‘gender contract’ that young adults have experienced will influence their sense of entitlement to support for work and family life. Findings indicate that participants perceived their entitlement to state and employer support differently across national context. However this is moderated by gender, parental and occupational status, and particularly by awareness of provisions in other countries in the case of state support, while perceived entitlement to employer support varies according to the specific policy considered, gender and perception of benefits to employers. Some implications for public policy makers and employers are discussed
Neurophysiologic effects of spinal manipulation in patients with chronic low back pain
<p>Abstract</p> <p>Background</p> <p>While there is growing evidence for the efficacy of SM to treat LBP, little is known on the mechanisms and physiologic effects of these treatments. Accordingly, the purpose of this study was to determine whether SM alters the amplitude of the motor evoked potential (MEP) or the short-latency stretch reflex of the erector spinae muscles, and whether these physiologic responses depend on whether SM causes an audible joint sound.</p> <p>Methods</p> <p>We used transcranial magnetic stimulation to elicit MEPs and electromechanical tapping to elicit short-latency stretch reflexes in 10 patients with chronic LBP and 10 asymptomatic controls. Neurophysiologic outcomes were measured before and after SM. Changes in MEP and stretch reflex amplitude were examined based on patient grouping (LBP vs. controls), and whether SM caused an audible joint sound.</p> <p>Results</p> <p>SM did not alter the erector spinae MEP amplitude in patients with LBP (0.80 ± 0.33 vs. 0.80 ± 0.30 μV) or in asymptomatic controls (0.56 ± 0.09 vs. 0.57 ± 0.06 μV). Similarly, SM did not alter the erector spinae stretch reflex amplitude in patients with LBP (0.66 ± 0.12 vs. 0.66 ± 0.15 μV) or in asymptomatic controls (0.60 ± 0.09 vs. 0.55 ± 0.08 μV). Interestingly, study participants exhibiting an audible response exhibited a 20% decrease in the stretch reflex (p < 0.05).</p> <p>Conclusions</p> <p>These findings suggest that a single SM treatment does not systematically alter corticospinal or stretch reflex excitability of the erector spinae muscles (when assessed ~ 10-minutes following SM); however, they do indicate that the stretch reflex is attenuated when SM causes an audible response. This finding provides insight into the mechanisms of SM, and suggests that SM that produces an audible response may mechanistically act to decrease the sensitivity of the muscle spindles and/or the various segmental sites of the Ia reflex pathway.</p
Adaptive Copy Number Evolution in Malaria Parasites
Copy number polymorphism (CNP) is ubiquitous in eukaryotic genomes, but the degree to which this reflects the action of positive selection is poorly understood. The first gene in the Plasmodium folate biosynthesis pathway, GTP-cyclohydrolase I (gch1), shows extensive CNP. We provide compelling evidence that gch1 CNP is an adaptive consequence of selection by antifolate drugs, which target enzymes downstream in this pathway. (1) We compared gch1 CNP in parasites from Thailand (strong historical antifolate selection) with those from neighboring Laos (weak antifolate selection). Two percent of chromosomes had amplified copy number in Laos, while 72% carried multiple (2–11) copies in Thailand, and differentiation exceeded that observed at 73 synonymous SNPs. (2) We found five amplicon types containing one to greater than six genes and spanning 1 to >11 kb, consistent with parallel evolution and strong selection for this gene amplification. gch1 was the only gene occurring in all amplicons suggesting that this locus is the target of selection. (3) We observed reduced microsatellite variation and increased linkage disequilibrium (LD) in a 900-kb region flanking gch1 in parasites from Thailand, consistent with rapid recent spread of chromosomes carrying multiple copies of gch1. (4) We found that parasites bearing dhfr-164L, which causes high-level resistance to antifolate drugs, carry significantly (p = 0.00003) higher copy numbers of gch1 than parasites bearing 164I, indicating functional association between genes located on different chromosomes but linked in the same biochemical pathway. These results demonstrate that CNP at gch1 is adaptive and the associations with dhfr-164L strongly suggest a compensatory function. More generally, these data demonstrate how selection affects multiple enzymes in a single biochemical pathway, and suggest that investigation of structural variation may provide a fast-track to locating genes underlying adaptation
Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study
Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised
Can human amblyopia be treated in adulthood?
Amblyopia is a common visual disorder that results in a spatial acuity deficit in the affected eye. Orthodox treatment is to occlude the unaffected eye for lengthy periods, largely determined by the severity of the visual deficit at diagnosis. Although this treatment is not without its problems (poor compliance, potential to reduce binocular function, etc) it is effective in many children with moderate to severe amblyopia. Diagnosis and initiation of treatment early in life are thought to be critical to the success of this form of therapy. Occlusion is rarely undertaken in older children (more than 10 years old) as the visual benefits are considered to be marginal. Therefore, in subjects where occlusion is not effective or those missed by mass screening programs, there is no alternative therapy available later in life. More recently, burgeoning evidence has begun to reveal previously unrecognized levels of residual neural plasticity in the adult brain and scientists have developed new genetic, pharmacological, and behavioral interventions to activate these latent mechanisms in order to harness their potential for visual recovery. Prominent amongst these is the concept of perceptual learning—the fact that repeatedly practicing a challenging visual task leads to substantial and enduring improvements in visual performance over time. In the normal visual system the improvements are highly specific to the attributes of the trained stimulus. However, in the amblyopic visual system, learned improvements have been shown to generalize to novel tasks. In this paper we ask whether amblyopic deficits can be reduced in adulthood and explore the pattern of transfer of learned improvements. We also show that developing training protocols that target the deficit in stereo acuity allows the recovery of normal stereo function even in adulthood. This information will help guide further development of learning-based interventions in this clinical group
- …