Sympathetic Nervous System Reactivity in Women Following Preeclamptic Pregnancies

Women who have had preeclamptic pregnancies are at risk for life-long cardiovascular disease. However, the factors contributing to this risk have yet to be established. Sympathetic nervous system dysregulation has been proposed to contribute to cardiovascular dysfunction during preeclamptic pregnancies. Therefore, we examined muscle sympathetic nerve activity (MSNA) at baseline and during a chemoreflex stimulus in women 6-24 months postpartum following a preeclamptic pregnancy (PE; n=6, age 28±2 y, BMI 27±3 kg/m2, 17±4 months postpartum). We hypothesized that MSNA responses to apnea would be greater in PE relative to control subjects, that is, women 6-24 months following a healthy pregnancy and with no history of disordered pregnancies (HP; n=6, 31±6 y, BMI 29±5 kg/m2, 17±4 months postpartum). Integrated MSNA recordings were obtained at baseline and during a voluntary end-inspiratory apnea. Baseline mean arterial pressure (MAP; 87±10 vs 95±10 mmHg, P=0.2), total peripheral resistance (TPR; 13±3 vs 14±1 mmHg/L/min, P=0.4), and heart rate (HR; 74±5 vs 74±13, P=0.9) were similar in PE vs HP. Baseline MSNA was higher in PE compared to HP (26±9 vs 14±6 bursts/100heartbeats, P\u3c0.01). The voluntary apnea was maintained for a similar duration in PE and HP (44±17 and 45±10 sec, P=0.9), without any difference in mean MAP (93±14 and 99±11, P=0.4), TPR (14±4 and 14±2, P=0.6), or HR (74±8 and 81±22, P=0.5) between groups. To discern between mild and moderate phases of chemoreflex stress, the apnea was divided into initial (i.e. first half) and latter (i.e. second half) phases for subsequent analyses. The initial phase of the apnea elicited a large increase in MSNA in the PE women which exceeded that observed in HP (37±13 vs 19±11, P=0.03, respectively). The peak sympathetic response observed in the latter half of the apnea was similar between PE and HP (56±21 vs 49±13 bursts/100hb, P=0.5). Thus, the sympathetic nervous system response to a mild chemoreflex stimulus is exaggerated in women who have had preeclampsia within the past 6-24 months relative to women without a history of preeclampsia. We have demonstrated that a recent history of preeclampsia is associated with chronic sympathetic activation as well as greater sympathetic reactivity. We propose these changes to the sympathetic nervous system contribute to the life-long risk for cardiovascular disease in formerly preeclamptic women. Funded by the Paul Titus Fellowship, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicin

Analysis Methods for Progressive Damage of Composite Structures

This document provides an overview of recent accomplishments and lessons learned in the development of general progressive damage analysis methods for predicting the residual strength and life of composite structures. These developments are described within their State-of-the-Art (SoA) context and the associated technology barriers. The emphasis of the authors is on developing these analysis tools for application at the structural level. Hence, modeling of damage progression is undertaken at the mesoscale, where the plies of a laminate are represented as a homogenous orthotropic continuum. The aim of the present effort is establish the ranges of validity of available models, to identify technology barriers, and to establish the foundations of the future investigation efforts. Such are the necessary steps towards accurate and robust simulations that can replace some of the expensive and time-consuming "building block" tests that are currently required for the design and certification of aerospace structures

Weight loss, glycemic control, and cardiovascular disease risk factors in response to differential diet composition in a weight loss program in type 2 diabetes: a randomized controlled trial.

ObjectiveTo test whether a weight loss program promotes greater weight loss, glycemic control, and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake.Research design and methodsThis randomized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling, with prepackaged foods in a planned menu during the initial phase, or to usual care (UC; two weight loss counseling sessions and monthly contacts).ResultsRelative weight loss was 7.4% (95% CI 5.7-9.2%), 9.0% (7.1-10.9%), and 2.5% (1.3-3.8%) for the lower fat, lower carbohydrate, and UC groups (P < 0.001 intervention effect). Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year (fasting glucose 141 [95% CI 133-149] vs. 159 [144-174] mg/dL, P = 0.023; hemoglobin A1c 6.9% [6.6-7.1%] vs. 7.5% [7.1-7.9%] or 52 [49-54] vs. 58 [54-63] mmol/mol, P = 0.001; triglycerides 148 [134-163] vs. 204 [173-234] mg/dL, P < 0.001). The lower versus higher carbohydrate groups maintained lower hemoglobin A1c (6.6% [95% CI 6.3-6.8%] vs. 7.2% [6.8-7.5%] or 49 [45-51] vs. 55 [51-58] mmol/mol) at 1 year (P = 0.008).ConclusionsThe weight loss program resulted in greater weight loss and improved glycemic control in type 2 diabetes

Assessment of Intralaminar Progressive Damage and Failure Analysis Using an Efficient Evaluation Framework

Reducing the timeline for development and certification for composite structures has been a long standing objective of the aerospace industry. This timeline can be further exacerbated when attempting to integrate new fiber-reinforced composite materials due to the large number of testing required at every level of design. computational progressive damage and failure analysis (PDFA) attempts to mitigate this effect; however, new PDFA methods have been slow to be adopted in industry since material model evaluation techniques have not been fully defined. This study presents an efficient evaluation framework which uses a piecewise verification and validation (V&V) approach for PDFA methods. Specifically, the framework is applied to evaluate PDFA research codes within the context of intralaminar damage. Methods are incrementally taken through various V&V exercises specifically tailored to study PDFA intralaminar damage modeling capability. Finally, methods are evaluated against a defined set of success criteria to highlight successes and limitations

Material Characterization for the Analysis of Skin/Stiffener Separation

Test results show that separation failure in co-cured skin/stiffener interfaces is characterized by dense networks of interacting cracks and crack path migrations that are not present in standard characterization tests for delamination. These crack networks result in measurable large-scale and sub-ply-scale R curve toughening mechanisms, such as fiber bridging, crack migration, and crack delving. Consequently, a number of unknown issues exist regarding the level of analysis detail that is required for sufficient predictive fidelity. The objective of the present paper is to examine some of the difficulties associated with modeling separation failure in stiffened composite structures. A procedure to characterize the interfacial material properties is proposed and the use of simplified models based on empirical interface properties is evaluated

Defining Megacities and Megaregions: The Need for U.S. Spatial Planning

Presented at the Megacities, Megaregions, and Spatial Planning Symposium, June 28-29, 2007, Atlanta, GA.Chapter 1: Megacities and Megaregions: Frontiers in Spatial PlanningPresented at 8:50 AM on June 28, 2007

Faster movement in non-habitat matrix promotes range shifts in heterogeneous landscapes

Ecologists often assume that range expansion will be fastest in landscapes composed entirely of the highest‐quality habitat. Theoretical models, however, show that range expansion depends on both habitat quality and habitat‐specific movement rates. Using data from 78 species in 70 studies, we find that animals typically have faster movement through lower‐quality environments (73% of published cases). Therefore, if we want to manage landscapes for range expansion, there is a trade‐off between promoting movement with nonhostile matrix, and promoting population growth with high‐quality habitat. We illustrate how this trade‐off plays out with the use of an exemplar species, the Baltimore checkerspot butterfly. For this species, we calculate that the expected rate of range expansion is fastest in landscapes with ~15% high‐quality habitat. Behavioral responses to nonhabitat matrix have often been documented in animal populations, but rarely included in empirical predictions of range expansion. Considering movement behavior could change land‐planning priorities from focus on high‐quality habitat only to integrating high‐ and low‐quality land cover types, and evaluating the costs and benefits of different matrix land covers for range expansion

Screening Young Adults for Prevalent Chlamydial Infection in Community Settings

Community-based testing may identify young adults in the general population with sexually transmitted chlamydial infection. To develop selective screening guidelines appropriate for community settings, the authors conducted a cross-sectional analysis of the National Longitudinal Study of Adolescent Health Wave III (April 2, 2001 – May 9, 2002)

Acupuncture and chiropractic care for chronic pain in an integrated health plan: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Substantial recent research examines the efficacy of many types of complementary and alternative (CAM) therapies. However, outcomes associated with the "real-world" use of CAM has been largely overlooked, despite calls for CAM therapies to be studied in the manner in which they are practiced. Americans seek CAM treatments far more often for chronic musculoskeletal pain (CMP) than for any other condition. Among CAM treatments for CMP, acupuncture and chiropractic (A/C) care are among those with the highest acceptance by physician groups and the best evidence to support their use. Further, recent alarming increases in delivery of opioid treatment and surgical interventions for chronic pain--despite their high costs, potential adverse effects, and modest efficacy--suggests the need to evaluate real world outcomes associated with promising non-pharmacological/non-surgical CAM treatments for CMP, which are often well accepted by patients and increasingly used in the community.</p> <p>Methods/Design</p> <p>This multi-phase, mixed methods study will: (1) conduct a retrospective study using information from electronic medical records (EMRs) of a large HMO to identify unique clusters of patients with CMP (e.g., those with differing demographics, histories of pain condition, use of allopathic and CAM health services, and comorbidity profiles) that may be associated with different propensities for A/C utilization and/or differential outcomes associated with such care; (2) use qualitative interviews to explore allopathic providers' recommendations for A/C and patients' decisions to pursue and retain CAM care; and (3) prospectively evaluate health services/costs and broader clinical and functional outcomes associated with the receipt of A/C relative to carefully matched comparison participants receiving traditional CMP services. Sensitivity analyses will compare methods relying solely on EMR-derived data versus analyses supplementing EMR data with conventionally collected patient and clinician data.</p> <p>Discussion</p> <p>Successful completion of these aggregate aims will provide an evaluation of outcomes associated with the real-world use of A/C services. The trio of retrospective, qualitative, and prospective study will also provide a clearer understanding of the decision-making processes behind the use of A/C for CMP and a transportable methodology that can be applied to other health care settings, CAM treatments, and clinical populations.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01345409">NCT01345409</a></p

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society