Integrative Treatment for Children with Cerebral Palsy

Cerebral palsy is a highly prevent motor disorder that is well studied but not necessarily well understood. Caused through various damaged neural mechanisms, cerebral palsy has wide spread implications on both physiological and psychological health. Through use of both occupational and constraint-induced therapy, improvements in motor movements can be seen but the issue of psychology well being is not addressed. The author argues for the use of longitudinal studies in order to better understand the impact of various therapeutic methods

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] >= 50 copies/mL) and VL = 50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Rapid coastal deoxygenation due to ocean circulation shift in the NW Atlantic.

Global observations show that the ocean lost approximately 2% of its oxygen inventory over the last five decades 1-3, with important implications for marine ecosystems 4, 5. The rate of change varies with northwest Atlantic coastal waters showing a long-term drop 6, 7 that vastly outpaces the global and North Atlantic basin mean deoxygenation rates 5, 8. However, past work has been unable to resolve mechanisms of large-scale climate forcing from local processes. Here, we use hydrographic evidence to show a Labrador Current retreat is playing a key role in the deoxygenation on the northwest Atlantic shelf. A high-resolution global coupled climate-biogeochemistry model 9 reproduces the observed decline of saturation oxygen concentrations in the region, driven by a retreat of the equatorward-flowing Labrador Current and an associated shift toward more oxygen-poor subtropical waters on the shelf. The dynamical changes underlying the shift in shelf water properties are correlated with a slowdown in the simulated Atlantic Meridional Overturning Circulation 10. Our results provide strong evidence that a major, centennial-scale change of the Labrador Current is underway, and highlight the potential for ocean dynamics to impact coastal deoxygenation over the coming century

Development of a proficiency-based virtual reality simulation training curriculum for laparoscopic appendicectomy

This paper was presented at the 10th Annual Academic Surgical Congress (ASC), 3–5 February 2015 in Las Vegas, NV, USA.Background: Proficiency-based virtual reality (VR) training curricula improve intraoperative performance, but have not been developed for laparoscopic appendicectomy (LA). This study aimed to develop an evidence-based training curriculum for LA. Methods: A total of 10 experienced (>50 LAs), eight intermediate (10–30 LAs) and 20 inexperienced (<10 LAs) operators performed guided and unguided LA tasks on a high-fidelity VR simulator using internationally relevant techniques. The ability to differentiate levels of experience (construct validity) was measured using simulator-derived metrics. Learning curves were analysed. Proficiency benchmarks were defined by the performance of the experienced group. Intermediate and experienced participants completed a questionnaire to evaluate the realism (face validity) and relevance (content validity). Results: Of 18 surgeons, 16 (89%) considered the VR model to be visually realistic and 17 (95%) believed that it was representative of actual practice. All ‘guided’ modules demonstrated construct validity (P < 0.05), with learning curves that plateaued between sessions 6 and 9 (P < 0.01). When comparing inexperienced to intermediates to experienced, the ‘unguided’ LA module demonstrated construct validity for economy of motion (5.00 versus 7.17 versus 7.84, respectively; P < 0.01) and task time (864.5 s versus 477.2 s versus 352.1 s, respectively, P < 0.01). Construct validity was also confirmed for number of movements, path length and idle time. Validated modules were used for curriculum construction, with proficiency benchmarks used as performance goals. Conclusion: A VR LA model was realistic and representative of actual practice and was validated as a training and assessment tool. Consequently, the first evidence-based internationally applicable training curriculum for LA was constructed, which facilitates skill acquisition to proficiency.Pramudith Sirimanna and Marc A. Gladma

What Can Hydrography Between the New England Slope, Bermuda and Africa Tell us About the Strength of the AMOC Over the Last 90 years?

The Gulf Stream is the only pathway in the subtropical North Atlantic by which warm water flows poleward. This transport of warm water and return of cold water at depth is called the Atlantic Meridional Overturning Circulation (AMOC). The dynamic method is applied to hydrocasts collected since the 1930s to estimate upper-ocean transport (0–1,000 m) between the U.S. Continental Slope and Bermuda and separately to Africa with focus on the longest directly observable timescale. Calculating transport between the Slope and Bermuda eliminates the Gulf Stream\u27s northern and southern recirculation gyres, while calculations between the Slope and Africa remove all other recirculating geostrophic flow. The net Slope-Bermuda upper-ocean transport is estimated to be 41.1 ± 0.4 Sv, decreasing by 2.0 ± 0.8 Sv between 1930 and 2020. The AMOC contribution is 18.4 ± 0.6 Sv, decreasing by 0.4 ± 0.6 Sv between 1930 and 2020

Gulf Stream rings may rival atmospheric iron supply to the North Atlantic subtropical gyre

Substantial amounts of nitrogen fixation occur in the North Atlantic subtropical gyre, due to the activity of cyanobacteria with high iron requirements. Iron is delivered to this region by dust from the Sahara Desert. However, this dust deposition is typically localized and episodic. Therefore, other sources of iron may also be important. Here, we report observations of dissolved iron concentrations in a Gulf Stream cold-core ring, which transported iron-rich water from near the continental slope into the subtropical gyre. We find that iron concentrations were elevated in the ring compared with subtropical waters, reflecting its source waters. Using iron data from these source waters and the identification of ring activity in satellite data, we estimate that cold-core rings provide a net flux of 0.3 ± 0.17 × 108 mol Fe yr−1 across the northwestern gyre edge, on the order of 15% of our median estimates of gyre-wide supply of iron by dust deposition. We suggest that iron supply from cold-core rings is an important source of iron to the northwestern gyre edge. We conclude that mesoscale ocean circulation features may play an important role in subtropical nutrient and carbon cycling

Do All Integrase Strand Transfer Inhibitors Have the Same Lipid Profile? Review of Randomised Controlled Trials in Naïve and Switch Scenarios in HIV-Infected Patients

In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies

Clinical perspectives on human genetic screening to prevent nevirapine toxicity

Nevirapine is one of the most extensively prescribed antiretroviral drugs worldwide. However, a concern is increased risk for severe toxicity when antiretroviral-naive individuals with higher CD4 T-cell counts initiate nevirapine-containing regimens. Several genetic variants are associated with nevirapine toxicities. The authors used data from a previous study to anticipate potential consequences of genetic screening to prevent nevirapine adverse events. That study enrolled cohorts of African, Asian and European descent in 11 countries, including 276 patients who had experienced severe cutaneous and/or hepatic adverse events with nevirapine-containing regimens and 587 matched nevirapine-tolerant controls. Associations were identified with HLA-Cw*04, HLA-B*35, HLA-DRB*01 and CYP2B6 516G>T (rs3745274); however, positive predictive values for these genetic markers were low, and most nevirapine-associated adverse events occurred in patients without these markers. Unless better genetic predictors are identified, nevirapine toxicity is best avoided by continuing to follow current prescribing guidelines that are based largely on CD4 T-cell criteria