887 research outputs found
Combination of drug level measurement and parasite genotyping data for improved assessment of amodiaquine and sulfadoxine-pyrimethamine efficacies in treating Plasmodium falciparum malaria in Gabonese children
Controlling the carrier-envelope phase of few-cycle focused laser beams with a dispersive beam expander
We report on a procedure to focalize few-cycle laser pulses in dispersive media with controlled waveform. Stationarity of the carrierenvelope phase for extended depth of focus is attained by shaping the spatial dispersion of the ultrashort beam. An adjustable group velocity is locally tuned in order to match a prescribed phase velocity at focus. A hybrid diffractive-refractive lens system is proposed to drive the wavefield to an immersion microscope objective under convenient broadband modulation. Numerical simulations demonstrate robustness over positioning of this dispersive beam expander
Development of exchange lists for M editerranean and H ealthy E ating D iets: implementation in an intervention trial
Background There has been little research published on the adaptation of diabetic exchange list diet approaches for the design of intervention diets in health research despite their clinical utility. The exchange list approach can provide clear and precise guidance on multiple dietary changes simultaneously. The present study aimed to develop exchange list diets for M editerranean and H ealthy E ating, and to evaluate adherence, dietary intakes and markers of health risks with each counselling approach in 120 subjects at increased risk for developing colon cancer. Methods A randomised clinical trial was implemented in the USA involving telephone counselling. The M editerranean diet had 10 dietary goals targeting increases in mono‐unsaturated fats, n ‐3 fats, whole grains and the amount and variety of fruits and vegetables. The Healthy Eating diet had five dietary goals that were based on the US H ealthy P eople 2010 recommendations. Results Dietary compliance was similar in both diet arms, with 82–88% of goals being met at 6 months, although subjects took more time to achieve the M editerranean goals than the H ealthy E ating goals. The relatively modest fruit and vegetable goals in the Healthy Eating arm were exceeded, resulting in fruit and vegetable intakes of approximately eight servings per day in each arm after 6 months. A significant ( P < 0.05) weight loss and a decrease in serum C ‐reactive protein concentrations were observed in the overweight/obese subgroup of subjects in the M editerranean arm in the absence of weight loss goals. Conclusions Counselling for the M editerranean diet may be useful for both improving diet quality and for achieving a modest weight loss in overweight or obese individuals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108685/1/jhn12158.pd
Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study
<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p>
<p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p>
<p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p>
<p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p>
Pasireotide versus octreotide in acromegaly: A head-to-head superiority study
Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control.
Objective: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly.
Design and Setting: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries.
Patients: A total of 358 patients with medically naive acromegaly (GH > 5 mu g/L or GH nadir >= 1 mu g/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging.
Interventions: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to pasireotide LAR 60 mg or octreotide LAR 30 mg was permitted, but not mandatory, if GH >= 2.5 mu g/L and/or IGF-1 was above the upper limit of normal.
Main Outcome Measure: The main outcome measure was the proportion of patients in each treatment arm with biochemical control (GH <2.5 mu g/L and normal IGF-1) at month 12.
Results: Biochemical control was achieved by significantly more pasireotide LAR patients than octreotide LAR patients (31.3% vs 19.2%; P = .007; 35.8% vs 20.9% when including patients with IGF-1 below the lower normal limit). In pasireotide LAR and octreotide LAR patients, respectively, 38.6% and 23.6% (P = .002) achieved normal IGF-1, and 48.3% and 51.6% achieved GH <2.5 mu g/L. 31.0% of pasireotide LAR and 22.2% of octreotide LAR patients who did not achieve biochemical control did not receive the recommended dose increase. Hyperglycemia-related adverse events were more common with pasireotide LAR (57.3% vs 21.7%).
Conclusions: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly
A phenomenological study of instructional leadership and preparation: perspective of urban principals
The role of the principal as an instructional leader has continued to change since the 1970s. Our understanding of the complexity and ambiguity of the role has grown and the focus shifted from management and supervision to one of building capacity for shared leadership and implementing second order change. This phenomenological study was undertaken to uncover perceptions of urban principals have regarding their view and implementation of instructional leadership and challenges that affect implementation. Qualitative methods of in depth interviewing, on site observation and artifact collection were used to collect data from 10 elementary and 2 middle school principals.An analysis of interview data revealed several themes regarding how principals view their instructional leadership role and how they implement the role. First, principals perceive 1) themselves to be the instructional leader of their school; 2) the role to be important, complex and multifaceted; and 3) it as only one of many roles they have. Second, they perceive themselves implementing the role through 1) provision of professional development; 2) monitoring instruction; and 3) building relationships. Principals perceived their instructional leadership to be challenged by 1) limited time to monitor instruction and 2) not having enough staff for the delegation non-instructional duties. Artifact analysis revealed that principals do provide professional development and monitor instruction. Overall, artifacts did not show the content, format or context in which professional development occurred. Evidence of professional development linked to building capacity in others toward shared leadership or to address second order change was also not present.A major recommendation of this study recognizes that university programs designed to prepare principals for instructional leadership have not kept pace with changes in the role. The recommendation suggests that universities might consider using the principles of second order change to design preparation programs characterized by a thoughtful mixture of research, theory, practitioner voices, course work, reflections and authentic learning experiences that will result in principals being prepared to 1) effectively build capacity in others to participate in shared leadership; and 2) lead deep change in schools that will result in increased numbers of students achieving at higher levels.Ph.D., Education -- Drexel University, 200
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Rigorous characterization of acoustic-optical interactions in silicon slot waveguides by full-vectorial finite element method
For the first time detailed interactions between optical and acoustic modes in a silicon slot waveguide are presented. A new computer code has been developed by using a full-vectorial formulation to study the acoustic modes in optical waveguides. The results have shown that the acoustic modes in an optical slot waveguide are not purely longitudinal or transverse but fully hybrid in nature. The model allows the effects of Stimulated Brillouin Scattering and the associated frequency shift due to the interaction of these hybrid acoustic modes with the fully hybrid optical mode also to be presented
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