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Background: The integration of time with dietary patterns throughout a day, or temporal dietary patterns (TDPs), have been linked with dietary quality but relations to health are unknown.Objective: The association between TDPs and selected health status indicators and obesity, type 2 diabetes (T2D), and metabolic syndrome (MetS) was determined.Methods: The first-day 24-h dietary recall from 1627 nonpregnant US adult participants aged 20-65 y from the NHANES 2003-2006 was used to determine timing, amount of energy intake, and sequence of eating occasions (EOs). Modified dynamic time warping (MDTW) and kernel k-means algorithm clustered participants into 4 groups representing distinct TDPs. Multivariate regression models determined associations between TDPs and health status, controlling for potential confounders, and adjusting for the survey design and multiple comparisons (P <0.05/6).Results: A cluster representing a TDP with evenly spaced, energy balanced EOs reaching ≤1200 kcal between 06:00 to 10:00, 12:00 to 15:00, and 18:00 to 22:00, had statistically significant and clinically meaningful lower mean BMI (P <0.0001), waist circumference (WC) (P <0.0001), and 75% lower odds of obesity compared with 3 other clusters representing patterns with much higher peaks of energy: 1000-2400 kcal between 15:00 and 18:00 (OR: 5.3; 95% CI: 2.8, 10.1), 800-2400 kcal between 11:00 and 15:00 (OR: 4.4; 95% CI: 2.5, 7.9), and 1000-2600 kcal between 18:00 and 23:00 (OR: 6.7; 95% CI: 3.9, 11.6).Conclusions: Individuals with a TDP characterized by evenly spaced, energy balanced EOs had significantly lower mean BMI, WC, and odds of obesity compared with the other patterns with higher energy intake peaks at different times throughout the day, providing evidence that incorporating time with other aspects of a dietary pattern may be important to health status. [ABSTRACT FROM AUTHOR]

Introduction: Prior studies suggest overuse of nonrecommended lung cancer screening tests in U.S. community practice and underuse of recommended tests.Methods: Data from the 2010 and 2015 National Health Interview Surveys was analyzed from 2016 to 2018. Prevalence, populations, and number of chest computed tomography (CT) and chest x-ray tests were estimated for people who did and did not meet U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening, among people aged ≥40 years without lung cancer.Results: In 2015, among those who met USPSTF criteria, 4.4% (95% CI=3.0%, 6.6%), or 360,000 (95% CI=240,000, 535,000) people reported lung cancer screening with a chest CT; and 8.5% (95% CI=6.5%, 11.1%), or 689,000 (95% CI=526,000, 898,000) people reported a chest x ray. Among those who did not meet USPSTF criteria, 2.3% (95% CI=2.0%, 2.6%), or 3,259,000 (95% CI=2,850,000, 3,724,000) people reported a chest x ray; and 1.3% (95% CI=1.1%, 1.5%), or 1,806,000 (95% CI=1,495,000, 2,173,000) people reported a chest CT. The estimated population meeting USPSTF criteria for lung cancer screening in 2015 was 8,098,000 (95% CI=7,533,000, 8,702,000), which was smaller than the 9,620,000 people (95% CI=8,960,000, 10,325,000) in 2010.Conclusions: The number of adults inappropriately screened for lung cancer greatly exceeds the number screened according to USPSTF recommendations, the prevalence of appropriate lung cancer screening is low, and the population meeting USPSTF criteria is shrinking. To realize the potential benefits of screening, better processes to appropriately triage eligible individuals to screening, plus screening with a USPSTF-recommended test, would be beneficial. [ABSTRACT FROM AUTHOR]

Background: Previous trials of iron supplementation in infancy did not consider maternal iron supplementation.Objective: This study assessed effects of iron supplementation in infancy and/or pregnancy on infant iron status, illnesses, and growth at 9 mo.Methods: Enrollment occurred from December 2009 to June 2012 in Hebei, China. Infants born to women in a pregnancy iron supplementation trial were randomly assigned 1:1 to iron [∼1 mg Fe/(kg · d) as oral iron proteinsuccynilate] or placebo from 6 wk to 9 mo, excluding infants with cord ferritin <35 μg/L. Study groups were pregnancy placebo/infancy placebo (placebo/placebo), pregnancy placebo/infancy iron (placebo/iron), pregnancy iron/infancy placebo (iron/placebo), and pregnancy iron/infancy iron (iron/iron). The primary outcome was 9-mo iron status: iron deficiency (ID) by cutoff (≥2 abnormal iron measures) or body iron <0 mg/kg and ID + anemia (hemoglobin <110 g/L). Secondary outcomes were doctor visits or hospitalizations and weight or length gain from birth to 9 mo. Statistical analysis by intention to treat and dose-response (between number of iron bottles received and outcome) used logistic regression with concomitant RRs and general linear models, with covariate control as applicable.Results: Of 1482 infants randomly allocated, 1276 had 9-mo data (n = 312-327/group). Iron supplementation in infancy, but not pregnancy, reduced ID risk: RRs (95% CIs) were 0.89 (0.79, 0.998) for placebo/iron compared to placebo/placebo, 0.79 (0.63, 0.98) for placebo/iron compared to iron/placebo, 0.87 (0.77, 0.98) for iron/iron compared to placebo/placebo, and 0.86 (0.77, 0.97) for iron/iron compared to iron/placebo. However, >60% of infants still had ID at 9 mo. Receiving more bottles of iron in infancy was associated with better infant iron status at 9 mo but only among iron-supplemented infants whose mothers were also iron supplemented (i.e., the iron/iron group). There were no group differences in hospitalizations or illnesses and no adverse effects on growth overall or among infants who were iron sufficient at birth.Conclusions: Iron supplementation in Chinese infants reduced ID at 9 mo without adverse effects on growth or illness. Effects of iron supplementation in pregnancy were observed only when higher amounts of iron were distributed in infancy. This trial was registered at clinicaltrials.gov as NCT00613717. [ABSTRACT FROM AUTHOR]

Background: Medial wedged foot orthoses are frequently prescribed to reduce retropatellar stress in patients with patellofemoral pain (PFP) by controlling calcaneal eversion and internal rotation of the tibia. During activities of daily living, the highest patella loads occur during stair descent, but the effect of foot orthoses during stair descent remains unclear.Research Question: The purpose of this study was to compare the kinematics, kinetics and muscle activation during a step descent task in healthy volunteers using three designs of foot orthoses (insoles).Methods: Sixteen healthy subjects with a mean age of 25.7 years, BMI of 23.3, and +5 Foot Posture Index were recruited. Subjects performed a step down task from 20 cm using a 5o rearfoot medial wedge (R), a 5o rearfoot and forefoot medial wedge (R/F), and a control flat insole (C).Results: Significant improvements in control were seen in the R and R/F insoles over the C insole in the foot and at the ankle and hip kinematics. The R and R/F insoles increased the knee adduction moments, but reduced knee internal rotation moment compared to the C insole. Abductor hallucis (AH) activity was reduced with both insoles, whereas tibialis anterior (TA) activity was reduced with the R insole only.Significance: Foot orthoses can change joint mechanics in the foot and lower limbs providing greater stability and less work done by AH and TA muscles. This data supports the use of foot orthoses to provide functional benefits during step descent, which may benefit patients with PFP. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the learning process of knee osteoarthritis (KOA) patients learning to change their foot progression angle (FPA) over a six-week toe-in gait training program. Sixteen patients with medial KOA completed a six-week toe-in gait training program with real-time biofeedback. Patients walked on an instrumented treadmill while receiving real-time feedback on their foot progression angle (FPA) with reference to a target angle. The FPA difference (difference between target and actual FPA) was analyzed during i) natural walking, ii) walking with feedback, iii) walking without feedback and iv) walking with a dual-task at the start and end of the training program. Self-reported difficulty and abnormality and time spent walking and training were also analyzed. The FPA difference during natural walking was significantly decreased from median 6.9 to median 3.6° i.e. by 3.3° in week six (p < 0.001); adding feedback reduced FPA difference to almost zero. However the dual-task condition increased the FPA difference at week one compared to the feedback condition (median difference: 1.8°, p = 0.022), but after training this effect was minimized (median difference: 0.6°, p = 0.167). Self-reported abnormality and difficulty decreased from median 5 to 3 and from median 6 to 3 on the NRS respectively (p < 0.05). Patients with medial KOA could reduce the FPA difference during natural walking after the gait retraining program, with some evidence of a reduction in the cognitive demand needed to achieve this. Automation of adaptions might need support from more permanent feedback using wearable technologies. [ABSTRACT FROM AUTHOR]

Background: The relative length of the second and fourth fingers (2D:4D) may be a sex-linked correlate of prenatal androgen exposure. However, the nature of the sex-linkage is controversial, with evidence for both X- and Y-linkage of the 2D:4D phenotype.Aims: To examine transgenerational effects relating to sex-linkage. In addition, assortative mating on 2D:4D was considered, as well as associations between 2D:4D and age and sex.Study Design: A family study was conducted. Parents and offspring completed a demographic questionnaire, and digit ratios were calculated from photocopies of participants' hands.Subjects: We recruited and phenotyped 585 individuals attending a cultural festival in Wales. 2D:4D information was available for 47 mother-son dyads, 70 mother-daughter dyads, 31 father-son dyads and 30 father-daughter dyads.Outcome Measures: Correlations between 2D:4D of parents and children, as well as between mothers and fathers were conducted. 2D:4D was also examined in relation to age and sex.Results and Conclusions: There was a sex difference in 2D:4D (males

Background: The efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported.Methods: Across study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2. Participants (18-65 y) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20-70mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores ≥18 and <50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAEs).Results: Least squares mean (95% CI) treatment differences (LDX-placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [-1.7, 2.0], P=0.883) or study 2 (-0.5 [-2.3, 1.3], P=0.583). The only TEAE reported by >5% of LDX participants at twice the placebo rate in both studies was dry mouth.Limitations: Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response.Conclusion: Contrary to expectations, LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare a developmental optical coherence tomography (OCT) based contact lens inspection instrument to a widely used geometric inspection instrument (Optimec JCF), to establish the capability of a market focused OCT system.Methods: Measurements of 27 soft spherical contact lenses were made using the Optimec JCF and a new OCT based instrument, the Optimec is830. Twelve of the lenses analysed were specially commissioned from a traditional hydrogel (Contamac GM Advance 49%) and 12 from a silicone hydrogel (Contamac Definitive 65), each set with a range of back optic zone radius (BOZR) and centre thickness (CT) values. Three commercial lenses were also measured; CooperVision MyDay (Stenfilcon A) in -10D, -3D and +6D powers. Two measurements of BOZR, CT and total diameter were made for each lens in temperature controlled saline on both instruments.Results: The results showed that the is830 and JCF measurements were comparable, but that the is830 had a better repeatability coefficient for BOZR (0.065mm compared to 0.151mm) and CT (0.008mm compared to 0.027mm). Both instruments had similar results for total diameter (0.041mm compared to 0.044mm).Conclusions: The OCT based instrument assessed in this study is able to match and improve on the JCF instrument for the measurement of total diameter, back optic zone radius and centre thickness for soft contact lenses in temperature controlled saline. [ABSTRACT FROM AUTHOR]

Objective: Most women diagnosed with unilateral breast cancer without BRCA1 or BRCA2 mutations are at low risk of contralateral breast cancer. Contralateral Prophylactic Mastectomy (CPM) decreases the relative risk of contralateral breast cancer, but may not increase life expectancy; yet international uptake is increasing. This study applied protection motivation theory (PMT) to determine factors associated with women's intentions to undergo CPM.Methods: Three hundred eighty-eight women previously diagnosed with unilateral breast cancer and of negative or unknown BRCA1 or BRCA2 status were recruited from an advocacy group's research database. Participants completed measures of PMT constructs based on a common hypothetical CPM decision-making scenario.Results: PMT constructs explained 16% of variance in intentions to undergo CPM. Response efficacy (CPM's advantages) and response costs (CPM's disadvantages) were unique individual predictors of intentions.Conclusion: Decision-making appears driven by considerations of the psychological, cosmetic and emotional advantages and disadvantages of CPM. Overestimations of threat to life from contralateral breast cancer and survival benefit from CPM also appear influential factors.Practice Implications: Patients require balanced and medically accurate information regarding the pros and cons of CPM, survival rates, and recurrence risks to ensure realistic and informed decision-making. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate self-reported diabetes and age at diagnosis among a sample of the British population, using general practitioners (GPs) as the reference standard. Using data from the Medical Research Council National Survey of Health and Development (NSHD), self-reported diabetes was determined either in response to a direct question at five follow-ups between 1977 and 2010, or from other self-reported medical information. A validation questionnaire was sent to the GP for all participants who reported a diagnosis of diabetes and gave permission to contact their GP (172). The validity of self-reported diabetes was assessed by calculating the percentage of self-reported diabetes cases that were confirmed by their GP, i.e. the positive predictive value (PPV). The difference between self-reported and GP-confirmed age at diagnosis was analysed with a Bland-Altman plot. Completed questionnaires were obtained from 157 GPs (91.2%). Of these, 149 confirmed their patient self-reported diabetes diagnosis (PPV=94.9%). Results were similar when self-reported diabetes was assessed by responses to direct questions only (PPV=95.4%). The average difference between self-reported and GP-reported age at diagnosis was 0.6 years (95% CI 0.2-1.1). We conclude that among the British population questionnaires are a valid method to assess GP-diagnosed diabetes, as measured by responses to a direct question or by patient-reported medical information. [ABSTRACT FROM AUTHOR]

The task of stepping over obstacles is known to be particularly risky for persons post stroke. A kinetic analysis informing on the movement strategies used to ensure clearance of the leading limb over an obstacle is, however, lacking. We examined obstacle avoidance strategies in six community dwelling stroke survivors comparing the use of paretic and non-paretic limb as the leading limb for clearance over obstacles measuring 7.5% and 15% of their total leg length. Subjects were able to increase foot clearance height in both limbs in order to avoid the two obstacles. Obstacle clearance with the non-paretic limb leading was associated with positive knee flexor work that increased when stepping over each obstacle, thus showing a normal knee strategy that flexes both the knee and the hip for foot clearance. There was also slightly increased hip flexor contribution for non-paretic obstacle clearance that was the same for both obstacle heights. When the paretic limb led during obstacle clearance, there was also evidence of an increased knee flexor moment, suggesting a residual knee strategy, but it was less pronounced than for the non-paretic limb and was assisted by greater vertical hip elevation and additional positive hip flexor work that both gained greater importance with increased obstacle height. These findings suggest that rehabilitation should explore the ability to improve the residual, but less powerful, knee flexor strategy in the paretic limb in specific patients, with further promotion of a hip flexor and limb elevation strategy depending on patient deficits and obstacle height. [ABSTRACT FROM AUTHOR]

Objective: To identify and rank perceived personal benefits from parenting practices that promote intake of calcium-rich foods and beverages (CRF/B) by early adolescents. Methods: A convenience sample of parents/caregivers (n = 133) of early adolescents (10-13 years) from 6 states (CA, HI, MN, OH, OR, UT) participated in a qualitative study using a Nominal Group Technique process. Benefits identified by parents/caregivers were ranked by importance, given a score weight, and summed to create a total weighted score across states. Results: The top benefit from making CRF/B available was parent emotional rewards. The top benefit perceived by parents from role modeling intake of CRF/B and setting expectations for intake of CRB was child health promotion. Conclusions and Implications: Child health promotion and parent emotional rewards were important perceived benefits derived from CRF/B parenting practices, and thus, should be included as the focus of education to increase the frequency of these practices. [ABSTRACT FROM AUTHOR]

Background: In acute pain models, coadministration of low doses of morphine and oxycodone markedly enhanced analgesia relative to either opioid given alone. Enhanced analgesia with coadministration of morphine and oxycodone has also been reported in acute and chronic moderate to severe pain conditions during double- blind studies. Objective: The goal of this study was to compare the efficacy and tolerability of a flexible dose regimen of the morphine/oxycodone combination versus oxycodone/acet-aminophen and fixed low-dose morphine/oxycodone. Methods: This was a 5-center, randomized, open-label study of hospitalized patients (n = 44) with acute moderate to severe postoperative pain after total knee arthroplasty. Inpatients were randomized to a flexible dose regimen of morphine/oxycodone (3 mg/2 mg to 24 mg/16 mg), fixed low-dose morphine/oxycodone regimen (3 mg/2 mg), or oxycodone/acetaminophen (5 mg/325 mg). Treatment was initiated following surgery after intravenous (IV) morphine patient-controlled analgesia. An algorithm was evaluated for converting the patient-controlled analgesia morphine dose to an initial oral dose of morphine/oxycodone. The primary efficacy variable was the time-weighted sum of pain intensity difference from 0 to 48 hours. Results: The median values for the sum of the pain intensity difference from 0 to 48 hours for the morphine/oxycodone flexible dose and oxycodone/acetaminophen were similar and approximately twice that of fixed morphine/oxycodone 3 mg/2 mg (148.0, 139.5, and 71.3, respectively). Moderate to severe gastrointestinal adverse events occurred in 50% of patients in the oxycodone/acetaminophen group compared with 15% of the equianalgesic morphine/ oxycodone group. On several items of the Brief Pain Inventory (general activity, walking ability, and sleep), the morphine/oxycodone flexible dose produced greater benefit than oxycodone/acetaminophen. Conclusions: Flexible dose morphine/oxycodone was superior to low-dose morphine/oxycodone and comparable to oxycodone/acetaminophen. Flexible dose morphine/oxycodone-treated patients had a lower rate of moderate to severe nausea or vomiting than equianalgesic oxycodone/acetaminophen-treated patients. Thus, morphine/oxycodone offers an attractive alternative to oxycodone/acetaminophen for the management of moderate to severe postoperative pain. ClinicalTrials.gov: identifier: NCT00818493. [ABSTRACT FROM AUTHOR]

Abstract: Background: Results from studies with a combination of oral morphine and oxycodone in postsurgical patients demonstrate significant analgesia and a tolerability profile comparable to other pain medications at morphine-equivalent doses. However, an intravenous (IV) combination has not previously been studied. Objective: This study evaluated the efficacy and tolerability of IV morphine versus a combination of IV morphine and IV oxycodone in a 1:1 ratio. Methods: This was a 2-center, randomized, double-blind, active-controlled pilot trial of 40 patients who had undergone total hip replacement. After surgery, when pain levels reached ≥4 (on the 11-point Numerical Pain Rating Scale), patients were randomized to 1 of 2 treatment groups. In part 1 of the study, patients were dosed every 5 minutes for the first 65 minutes (up to 13 doses) with study drug, provided that vital signs criteria were met. After an initial loading dose of either morphine 1.5 mg coadministered with oxycodone 1.5 mg or morphine 3 mg alone, patients received IV morphine 1.5 mg or IV morphine 0.75 mg/IV oxycodone 0.75 mg every 5 minutes. If patients achieved a pain score of 2 or experienced intolerable adverse events to drug when stable, they were permitted to enter part 2. In part 2, patients received blinded study medication (IV morphine plus IV oxycodone [0.5 mg/0.5 mg] or 1 mg IV morphine alone) via patient-controlled analgesia (PCA) for 47 hours. Results: At baseline, treatment groups were comparable except for a higher proportion of females in the IV morphine group. Baseline pain intensity averaged 7 on the Numerical Pain Rating Scale of 0 to 10. One patient in the morphine group and 2 patients in the morphine/oxycodone group discontinued the study. The sum of the pain intensity differences from baseline to 65 minutes during the dose-titration phase was 1.8 for morphine alone versus 2.7 for morphine/oxycodone (P = 0.12); these values occurred at the same median number of doses (12) for each group. In part 2 (PCA dosing) of the study, similar levels of analgesia were achieved. During the study, 24% of the IV morphine/oxycodone group and 37% of the IV morphine group experienced nausea, and 10% of the IV morphine/oxycodone group and 16% of the IV morphine group had emesis. Two patients in the IV morphine/oxycodone group and 4 in the IV morphine alone group experienced oxygen desaturation. Conclusions: The combination of IV morphine and oxycodone provided pain relief with an acceptable tolerability profile in these patients experiencing moderate to severe postoperative pain. However, as an explorative pilot study, the power was not adequate to demonstrate statistical significance for differences between IV morphine/oxycodone and IV morphine alone. European Clinical Trials Data Base registration code: EudraCT-No. 2008-008527-14. [Copyright &y& Elsevier]

Several proposed biotechnological applications of green fluorescent protein (GFP) are likely to result in its introduction into the food supply of domestic animals and humans. We fed pure GFP and diets containing transgenic canola expressing GFP to young male rats for 26 d to evaluate the potential toxicity and allergenicity of GFP. Animals (n = 8 per group) were fed either AIN-93G (control), control diet plus 1.0 mg of purified GFP daily, modified control diet with 200 g/kg canola (Brassica rapa cv Westar), or control diet with 200 g/kg transgenic canola containing one of two levels of GFP. Ingestion of GFP did not affect growth, food intake, relative weight of intestine or other organs, or activities of hepatic enzymes in serum. Comparison of the amino acid sequence of GFP to known food allergens revealed that the greatest number of consecutive amino acid matches between GFP and any food allergen was four, suggesting the absence of common allergen epitopes. Moreover, GFP was rapidly degraded during simulated gastric digestion. These data indicate that GFP is a low allergenicity risk and provide preliminary indications that GFP is not likely to represent a health risk. [ABSTRACT FROM AUTHOR]

Laparoscopic cholecystectomy is now considered the “gold standard” operation for patients with gallstone disease. A number of patients require conversion to an open cholecystectomy for the safe completion of the procedure. This study investigates how the etiology and incidence of conversion from laparoscopic to open cholecystectomy has changed over time. All 5884 patients undergoing laparoscopic cholecystectomy between March 1991 and June 2001 were prospectively collected in a database. A total of 310 patients (5.2%) had had their cholecystectomies converted to an open procedure. The mortality rate for these patients was 0.7%. Causes for conversion were inability to correctly identify anatomy (50%), “other” indications (16%), bleeding (14%), suspected choledocholithiasis (11%), and suspected bile duct injury (8%). After an initial learning curve in thin patients with symptomatic cholelithiasis, inclusion of patients with acute cholecystitis, morbid obesity, or a prior celiotomy resulted in a peak conversion rate of 11% by 1994. From 1994 to the first half of 2001, the conversion rate has declined significantly for all patients (10% to 1%), as well as for patients with acute cholecystitis (26% to 1%). Although unclear anatomy secondary to inflammation remains the most common reason for conversion, the impact of acute cholecystitis on the operative outcome has decreased with time. ( J Gastrointest Surg 2002;6:800–805.) [Copyright &y& Elsevier]

In ruminants, pancreatic alpha-amylase is the primary enzyme responsible for the initial hydrolysis of alpha-linked glucose in the small intestinal lumen. The objective of this experiment was to examine the effects of altered dietary starch and energy supply on the expression of pancreatic alpha-amylase mRNA, protein and activity in lambs. Wether lambs (n = 24; 28 +/- 0.5 kg body weight) were fed low or high starch diets at 1.2 or 1.8 x net energy of maintenance for at least 28 d before tissue collection. Lambs fed the high energy/high starch diet tended to have more pancreatic alpha-amylase protein (54.5 kDa; P: = 0.08) and had greater activity (P: = 0.03), but alpha-amylase mRNA (1.6 kb) tended to be lower (P: = 0.17). Additionally, rumen fluid total short-chain fatty acid concentration was greater (P: = 0.04) and plasma glucose concentration tended to be greater (P: = 0.07) in lambs fed the high energy/high starch diet. However, pancreatic trypsinogen protein (25. 5 kDa) and jejunal maltase activity were not influenced by dietary treatment, suggesting that different regulatory systems are involved in regulating the tissue protein or activity levels of these two enzymes compared with alpha-amylase. These data suggest that dietary regulation of pancreatic alpha-amylase expression in ruminants is complex and probably regulated by transcriptional and post-transcriptional events. [ABSTRACT FROM AUTHOR]

Objectives: The use of high-resolution in vivo confocal imaging may offer a clinically useful adjunct to standard methods for the diagnosis and screening of epithelial precancers. This study assesses the feasibility of real-time confocal reflectance imaging of cervical tissue and the use of acetic acid as a contrast agent to increase visualization of cell nuclei.Study Design: A confocal microscope was used to image cervical cells and colposcopically normal and abnormal cervical biopsy specimens. Images were obtained before and after the application of 6% acetic acid.Results: The confocal imaging system resolved subcellular detail throughout the entire epithelial thickness. Normal and abnormal tissues were clearly able to be differentiated. Addition of acetic acid enhanced nuclear signal in all acquired images.Conclusion: High-contrast reflected light images of cervical tissue are attainable in near real time. Acetic acid significantly increases light scattering from cell nuclei, which may partially explain why acetowhitening occurs. [ABSTRACT FROM AUTHOR]

Background: Limited research has focused on identifying the extent to which social networks impact the effectiveness of brief alcohol interventions delivered in trauma care settings.Objectives: The research presented here examines the extent to which the percent of heavy drinkers and percent of abstainers in one's social network moderates the effectiveness of a brief motivational intervention with and without a telephone booster on alcohol use among trauma patients.Method: Secondary data analyses were conducted using data from 596 participants (456males) who were recruited from three urban Level I trauma centers. Patients were randomized to one of the three intervention conditions: brief advice (BA; n = 200), brief motivational intervention (BMI; n = 203), and BMI with a telephone booster (BMI + B; n = 193). For the purpose of the present study, measures of alcohol-specific social network characteristics at baseline and alcohol use at 3- and 6-month follow-up were used.Results: At low percentages (0% to ~7%) of people in one's social network who are heavy drinkers, there was a negative, statistically significant effect of the BMI conditions versus the BA condition on alcohol use. However, percent of abstainers did not moderate the effects of the BMI conditions.Conclusion: The results suggest that the BMI and BMI + B conditions may be most effective among patients with no heavy drinkers in their social networks. BMIs may benefit from including a component that addresses having one or more heavy drinkers in one's social network. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesised that the ratio of length between the second and fourth fingers (2D:4D), commonly employed as an indicator of foetal sex hormone exposure, may be positively correlated between heterosexual partners.Aims: As previous evidence has been conflicting, our study aimed to determine whether intra-couple correlations exist for digit ratio variables, and if so, to estimate the size and direction of these effects.Study Design: We present a preregistered (osf.io/6jg8p) correlational study and quantitative meta-analysis of the available literature, and attempted to locate further published and unpublished data (i.e. 'grey literature') by contacting n = 248 researchers in the 2D:4D and related fields.Subjects: n = 58 heterosexual dating couples from the UK took part in our empirical study, and the meta-analysis included data from k = 11 samples.Outcome Measures: We measured digit ratio for the right hand (R2D:4D), left hand (L2D:4D), and average of both hands (M2D:4D), as well as the right-left-difference (D[R-L]).Results: We found no evidence of significant positive intra-couple correlations in our own data, but a significant (positive) meta-analytic effect size estimate emerged for R2D:4D (r = 0.072, p = 0.014). The meta-analytic effects for L2D:4D (r = 0.043, p = 0.303), M2D:4D (r = 0.070, p = 0.225), and D[R-L] (r = 0.028, p = 0.649) were all in the same direction but not statistically significant. However, if the sample from Klimek et al. (2014, 2016) were omitted, meta-analysis would also yield a significant positive correlation for M2D:4D (r = 0.128, p = 0.001).Conclusions: Although our findings are based on a fairly small range of studies, which themselves provide a relatively small sample of participants, they do imply the intriguing possibility of small effects of positive assortment in relation to characteristics associated with the prenatal hormonal environment. [ABSTRACT FROM AUTHOR]

Background: This study aims to examine if risk of dementia differs between adult- and late-onset depression.Methods: 16,608 community-living dementia-free older adults were followed for 6 years to the outcome of incident dementia. Depression was diagnosed according to international diagnostic guidelines. Depression in adulthood or late life was categorized using age 65 as cutoff. Hazard ratio for dementia was estimated using Cox regression analysis.Results: People with depression in adulthood only did not have higher dementia incidence, suggesting those in remission from adult-onset depression are not at greater risk of dementia. Conversely, having depression in both adulthood and late life was associated with higher dementia risk, and improvement in depression in late life was associated with lower risk, suggesting persistent or recurrent lifetime depression is a risk factor for dementia. Those with depression in late life only were not associated with higher dementia risk after controlling for the longitudinal changes in depressive symptoms, consistent with late-onset depression being a prodrome of dementia.Limitations: Reverse causation is a potential limitation. This was minimized by careful ascertainment of depression and dementia cases, exclusion of individuals with suspected dementia at baseline and those who developed dementia within 3 years after baseline, and controlling for various important confounders.Conclusions: Risk of incident dementia varies with presence and resolution of depression at different ages. Further studies are needed to test whether treating adult-onset depression may prevent dementia. Older adults with a history of depression present for an extended time should be monitored for cognitive decline. [ABSTRACT FROM AUTHOR]

Background: To gain new insights into the origin and prevention of diagnostic delays in the evaluation of hematuria in an electronic health record (EHR)-based integrated care setting.Methods: We performed a retrospective review of 298 consecutive patients with new-onset hematuria at a Veterans Affairs facility from January 1, 2011 to December 31, 2013 excluding those where diagnostic evaluation was unnecessary (i.e., cystoscopy within 3 years prior). We collected data on presentation, such as red flags of painless gross hematuria (PGH) or asymptomatic microhematuria (AMH) and subsequent evaluation (imaging, urologic referral, and cystoscopy). Delay was defined when evaluation was not completed within 60 days. Logistic regression was performed to identify predictors of delay.Results: Of 201 patients, 149 had delays. PGH was present in 99 patients. These patients had a higher rate of urology referral within 1 year than patients with AMH (86.7% vs. 64.7%; P<0.01) and were more likely to undergo cystoscopy (75.8% vs. 52%; P<0.01). Delays occurred in 67% of PGH patients vs. 81% of AMH patients (OR 0.46; P = 0.02), and roughly a third were related to scheduling/coordination, patient-related issues, or delay in primary care referral. Bladder neoplasms were detected in 18% of patients with PGH and 2% of those with AMH.Conclusion: Delays in evaluation for hematuria occur commonly, regardless of strength of the red-flag. Many delays were preventable and could be targeted with interventions including EHR-based tracking systems or reformed scheduling practices. [ABSTRACT FROM AUTHOR]

Background: The differences and relationship between joint stiffness and leg stiffness can be used to characterize the lower limb behavior during different walking speeds.Research Question: This study aimed to investigate the differences in whole leg and lower limb joint stiffness at different walking speeds and the interactions between leg and lower limb joint stiffness.Methods: Twenty-seven healthy adults, seventeen males (age: 19.6 ± 2.2 years, height: 176.0 ± 6.0 cm, mass: 69.7 ± 8.9 kg), and ten females (age: 19.1 ± 1.9 years, height: 164.0 ± 3.0 cm, mass: 59.6 ± 3.8 kg), were recruited. Dynamic leg and joint stiffness were calculated during eccentric loading from data recorded using 3D infrared motion analysis and force plates at slow, normal, and fast walking speeds. Differences in dynamic stiffness, joint angles and moments were explored between the walking speeds using Repeated Measures ANOVA with Sidak post-hoc tests. Correlations between leg, joint stiffness, and walking speed were also explored.Results: The results indicated that the leg dynamic stiffness is decreased by walking speed, however, hip and ankle joint stiffness were increased (p < 0.001) and knee stiffness was unaffected. Leg stiffness showed no correlation with hip, knee, or ankle stiffness. A positive significant correlation was seen between hip and ankle stiffness (p < 0.01) and between knee and ankle stiffness (p < 0.001), however, no correlation was seen between hip and knee stiffness.Significance: These results suggest leg stiffness is not associated with lower limb joint stiffness during eccentric loading. This provides new information on the responses of ankle, knee and hip joint stiffness to walking speed. [ABSTRACT FROM AUTHOR]

Objective To assess qualitatively and quantitatively college students' perceived differences between a real meal, meal, and snack. Design A descriptive study design was used to administer an 11-item online survey to college students. Setting Two university campuses in the western US. Participants Pilot testing was conducted with 20 students. The final survey was completed by 628 ethnically diverse students. Main Outcome Measures Students' perceptions of the terms real meal , meal , and snack . Analysis Three researchers coded the data independently, reconciled differences via conference calls, and agreed on a final coding scheme. Data were reevaluated based on the coding scheme. Means, frequencies, Pearson chi-square, and t test statistics were used. Results More than half of students perceived a difference between the terms real meal and meal . Most (97.6%) perceived a difference between the terms meal and snack . A marked difference in the way students defined these terms was evident, with a real meal deemed nutritious and healthy and meeting dietary recommendations, compared with meals, which were considered anything to eat. Conclusions and Implications These findings suggest that the term real meal may provide nutrition educators with a simple phrase to use in educational campaigns to promote healthful food intake among college students. [ABSTRACT FROM AUTHOR]

Background and Aim: The Suicide Crisis Syndrome (SCS) is an evidence-based pre-suicidal cognitive and affective state predictive of short-term suicide risk. The most recent SCS formulation, proposed as a suicide-specific DSM diagnosis, features a feeling of Entrapment accompanied by four additional symptom clusters: Affective Disturbance; Loss of Cognitive Control; Hyperarousal; and Social Withdrawal. The aim of the present study was to revise the Suicide Crisis Inventory (SCI; Barzilay et al., 2020), a self-report measure assessing the presence of the SCS,in accordance with the current SCS formulation, as well as to assess the psychometric properties and clinical utility of its revised version, the Suicide Crisis Inventory-2 (SCI-2).Methods: The SCI-2, a 61-item self-report questionnaire, was administered to 421 psychiatric inpatients and outpatients at baseline. Prospective suicidal outcomes including suicidal ideation, preparatory acts, and suicidal attempts were assessed after one month. Internal structure and consistency were assessed with confirmatory factor analysis, convergent, discriminant, and current criterion validity. Receiver-operating characteristic (ROC) curves with Area under the Curve (AUC) were used to examine the predictive validity of the SCI-2 to prospective outcomes. Exploratory analyses assessed the predictive validity of the five SCI-2 dimensions.Results: The SCI-2 demonstrated excellent internal consistency (Cronbach's α = 0.971), good convergent, discriminant, and current criterion validity. The SCI-2 significantly predicted all three outcomes, and was the only significant predictor of suicidal attempts with AUC = 0.883.Discussion: The results of this study indicate that the SCI-2 is a valid and reliable tool to assess the presence and intensity of the Suicide Crisis Syndrome and to predict short-term prospective suicidal behaviors and attempts among psychiatric outpatients and inpatients regardless of patients' readiness to disclose suicidal ideation. [ABSTRACT FROM AUTHOR]

Introduction: Clinical preventive services can reduce mortality and morbidity, but Americans receive only half of the recommended care. Although wellness visits protect time for clinicians to review needs and discuss care with patients, studies have not shown that having a wellness visit improves health outcomes. This study seeks to understand the types of discussions and volume of care delivered during wellness visits.Methods: Using a sample of 1,008 patients scheduled for a wellness visit from 22 primary care clinicians across 3 states from 2018 to 2019, electronic health records were reviewed, and a subset of visits was audio recorded. The discussion and delivery of clinical preventive services, as recommended by the U.S. Preventive Services Task Force, were measured, and new diagnoses were identified from the clinical preventive services. Analyses were completed in 2020.Results: Even though patients were up to date with 80% of the recommended clinical preventive services 3 months after the visit, only 0.5% of patients were up to date with all the recommended clinical preventive services. On average, 6.9 clinical preventive service discussions occurred during each wellness visit on the basis of electronic health records review, and 7.7 clinical preventive services discussions occurred on the basis of audio recordings. An average of 0.4 new diagnoses was identified, including cancer diagnoses, cardiovascular risks, and infections.Conclusions: Wellness visits are an important time for patients and clinicians to discuss prevention strategies and to deliver recommended clinical preventive services, leading to the identification of previously unrecognized diagnoses. This will improve patients' health. Policies and incentives that promote wellness visits are important, and efforts are needed to deliver them to those most in need. [ABSTRACT FROM AUTHOR]

The past decade has witnessed a new wave of hospital-physician integration, with the fraction of hospitals owning any office-based physician practice increasing from 28% in 2009 to 53% in 2015 nationwide. We offer one of the first hospital-level longitudinal analyses in examining how hospital-physician integration affects hospital prices in the modern healthcare environment. We find a robust 3-5% increase in hospital prices following integration. There is little indication that hospital quality is commensurately higher or that patient mix has changed following integration. Our supplementary analyses point to stronger bargaining leverage and foreclosure of rival hospitals as potential mechanisms for the estimated price effects. [ABSTRACT FROM AUTHOR]

Background: Walking at a brisk pace is widely recommended to promote health. When partners walk together, walking activity is increased and maintained due to enhanced social support and accountability, but at least one person must adjust their gait speed. Decreased gait speed could compromise health benefits, which may be especially relevant for the aging population.Research Question: Do adults change gait speed when walking with their romantic partner, relative to walking alone, and is the change in speed affected by age or pathway conditions?Methods: Participants were 141 individuals from 72 romantic couples; age range 25-79 years. The three couple conditions were walking alone, walking with their partner, and walking while holding hands with their partner. The two pathway conditions were clear pathway and pathway with obstacles. Gait speed was modeled as a function of the couple conditions, pathway conditions, and covariates (gender, age, relationship duration, and physical activity) using mixed-effects (3-level) regression.Results: In both pathway conditions, both partners reduced speed when walking together (p < 0.001), and reduced speed further while holding hands (p < 0.001), when compared to walking alone. These effects were unchanged when covariates were included in the model. Further, speed was slower on the obstructed pathway for all participants, but the magnitude of slowing was greater with increasing age (p < 0.001) and in females (p=0.03).Significance: Across the adult lifespan, when walking together, both partners decreased gait speed by a clinically meaningful amount (≥0.05 m/s). While walking with a partner may increase walking activity due to social support, reduced speed when walking together may unintentionally reduce health benefits and gait quality in both partners. Future research should identify how health is impacted by the trade-off between increased walking activity and reduced gait speed when romantic partners walk together. [ABSTRACT FROM AUTHOR]

Background: Sensorimotor foot orthoses is an alternative concept, which in addition to mechanical effects, are designed to change muscle activation by altering sensory input to the plantar surface of the foot. However, there is little evidence of how these affect the kinematics of the foot during gait.Research Question: The aim of the study was to explore the immediate effect of calcaneal medial heel bars and retrocapital bars on foot kinematics during the stance phase of gait.Methods: Kinematic data were collected from 32 healthy individuals using an eight camera motion capture system and a six-degrees-of-freedom multi-segment foot model in three different orthotic conditions; calcaneal medial heel bar, retrocapital bar, and no orthosis. Vector field statistical analysis was performed to explore the effect of the orthotic conditions over the kinematic time series curves during stance phase. Peak median and interquartile ranges were also reported during the different phases of stance.Results: The calcaneal medial bar significantly decreased rearfoot eversion for the majority of the stance phase and compensatory increased midfoot eversion during the entire stance phase compared to the no orthosis condition. The retrocapital bar rotated the foot externally significantly abducting the rearfoot for the entire stance phase and the midfoot for the majority of stance phase.Significance: The calcaneal medial heel bar and retrocapital bar significantly altered the foot kinematics in a way that may benefit patients with abnormal pronation and intoeing gait. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC).Methods: This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis.Results: Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes.Conclusion: We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug. [ABSTRACT FROM AUTHOR]

Necuparanib, a rationally engineered low-molecular-weight heparin, combined with gemcitabine/nab-paclitaxel showed an encouraging safety and oncologic signal in a phase Ib trial. This randomised multicentre phase II trial evaluates the addition of necuparanib or placebo to gemcitabine/nab-paclitaxel in untreated metastatic pancreatic ductal adenocarcinoma (PDAC). Eligibility included 18 years, histologically or cytologically confirmed metastatic PDAC, measurable disease and Eastern Co-Operative Oncology Group performance status of 0–1. Patients were randomly assigned to necuparanib (5 mg/kg subcutaneous injection once daily) or placebo (subcutaneous injection once daily) and gemcitabine/nab-paclitaxel on days 1, 8 and 15 of 28-day cycles. The primary end-point was median overall survival (OS), and secondary end-points included median progression-free survival, response rates and safety. One-hundred ten patients were randomised, 62 to necuparanib arm and 58 to placebo arm. The futility boundary was crossed at a planned interim analysis, and the study was terminated by the Data Safety Monitoring Board. The median OS was 10.71 months (95% confidence interval [CI]: 7.95–11.96) for necuparanib arm and 9.99 months (95% CI: 7.85–12.85) for placebo arm (hazard ratio: 1.12, 95% CI: 0.66–1.89, P-value: 0.671). The necuparanib arm had a higher incidence of haematologic toxicity relative to placebo patients (83% and 70%). The addition of necuparanib to standard of care treatment for advanced PDAC did not improve OS. Safety was acceptable. No further development of necuparanib is planned although targeting the coagulation cascade pathway remains relevant in PDAC. NCT01621243 • Preclinical data have shown that necuparanib decreases tumour growth and metastatic spread in pancreas models. • Early phase Ib evaluation of gemcitabine, nab-paclitaxel and necuparanib indicated safety for the combination and promising clinical activity. • The addition of necuparanib to gemcitabine and nab-paclitaxel did not improve outcome over standard therapy. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase-9 (PDE9) reduces natriuretic peptide (NP) signaling and may be involved in the pathophysiology of heart failure (HF).Objectives: This study investigated for the first time the integrated hemodynamic, endocrine, and renal effects of phosphodiesterase-9 inhibition (PDE9-I).Methods: A total of 8 normal sheep and 8 sheep with pacing-induced HF received incremental intravenous boluses of PDE9-I (30, 100, and 300 mg PF-04749982 at 1-h intervals).Results: PDE9-I dose-dependently increased plasma cyclic guanosine monophosphate (cGMP) in normal sheep (p < 0.05) while concurrently reducing circulating atrial natriuretic peptide levels (p < 0.01). Similar trends were evident in HF, resulting in significant elevations in the cGMP/NP ratio in both states (p < 0.001 and p < 0.05, respectively). PDE9-I also produced progressive falls in arterial pressure (HF: p < 0.001), atrial pressure (Normal: p < 0.001; HF: p < 0.001), and peripheral resistance (HF: p < 0.001), and transiently increased cardiac output at the top dose (Normal: p < 0.05; HF: p < 0.001). Inhibition of PDE9 had a negligible effect on circulating hormones at the lower doses, but post-high dose, acutely increased renin activity (Normal: p < 0.001; HF: p < 0.05), vasopressin (Normal: p < 0.001; HF: p < 0.01), and cyclic adenosine monophosphate (HF: p < 0.001). Plasma aldosterone increased briefly after high-dose PDE9-I in normal sheep, and fell following the top dose in HF. PDE9-I dose-dependently increased urinary cGMP in both states (both p < 0.001). In HF, this was associated with increases in urine volume (p < 0.01), sodium excretion (p < 0.01), and creatinine clearance (p < 0.001).Conclusions: PDE9-I improves NP efficacy in conjunction with beneficial hemodynamic and renal effects in experimental HF. These results support a role for PDE9 in HF pathophysiology and suggest its inhibition may constitute a novel therapeutic approach to this disease. [ABSTRACT FROM AUTHOR]

Purpose: There is a growing population of cancer survivors at risk of treatment-related morbidity. This study investigated how potentially curative rectal cancer treatment influences subsequent function and health-related quality of life using data from a large-scale survey of patient-reported outcomes.Methods and Materials: All individuals 12 to 36 months after receiving a diagnosis of colorectal cancer in England were sent a survey in January 2013. The survey responses were linked with cancer registration, hospital admissions, and radiation therapy data through the National Cancer Registration and Analysis Service. Outcome measures were cancer specific (Functional Assessment of Cancer Therapy and Social Difficulties Inventory items related to fecal incontinence, urinary incontinence, and sexual difficulties) and generic (EuroQol EQ-5D).Results: Surveys were returned by 6713 (64.2%) of 10,452 patients with rectal cancer. Of these, 3998 patients were in remission after a major resection and formed the final analysis sample. Compared with those who had surgery alone, patients who received preoperative radiation therapy had higher odds of reporting poor bowel control (43.6% vs 33.0%; odds ratio [OR] = 1.55; 95% confidence interval [CI], 1.26-1.91), severe urinary leakage (7.2% vs 3.5%; OR = 1.69; 95% CI, 1.18-2.43), and severe sexual difficulties (34.4% vs 18.3%; OR = 1.73; 95% CI, 1.43-2.11). Patients who received long-course chemoradiotherapy reported significantly better bowel control than those who had short-course radiation therapy, with no difference for other outcomes. Respondents with a stoma present reported significantly higher levels of severe sexual difficulties and worse health-related quality of life than those who had never had a stoma or had undergone stoma reversal.Conclusions: This study demonstrated the feasibility of a large-scale assessment of patient-reported outcomes and provided "real-world" data regarding the effect of rectal cancer treatment. The results show that patients who receive preoperative radiation therapy reported poorer outcomes, particularly for bowel and sexual function, and highlighted the negative impact of a stoma. We hope that our experience will encourage researchers to perform similar studies in other healthcare systems. [ABSTRACT FROM AUTHOR]

Background: No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine.Methods: Data were pooled from five clinical ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR-diagnosed major depressive disorder (MDD) or bipolar depression received one subanesthetic (0.5 mg/kg) ketamine infusion over 40 min. Composite SI variable scores were analyzed using growth mixture modeling to generate SI response classes, and class membership predictors were evaluated using multinomial logistic regressions. Putative predictors included demographic variables and various peripheral plasma markers.Results: The best-fitting growth mixture model comprised three classes: Non-Responders (29%), Responders (44%), and Remitters (27%). For Responders and Remitters, maximal improvements were achieved by Day 1. Improvements in SI occurred independently of improvements in a composite Depressed Mood variable for Responders, and partially independently for Remitters. Indicators of chronic SI and self-injury were associated with belonging to the Non-Responder group. Higher levels of baseline plasma interleukin-5 (IL-5) were linked to Remitters rather than Responders.Limitations: Subjects were not selected for active suicidal thoughts; findings only extend to Day 3; and plasma, rather than CSF, markers were used.Conclusion: The results underscore the heterogeneity of SI response to ketamine and its potential independence from changes in Depressed Mood. Individuals reporting symptoms suggesting a longstanding history of chronic SI were less likely to respond or remit post-ketamine. [ABSTRACT FROM AUTHOR]

Background: Affective problems increase the risk of dementia and cognitive impairment, yet the life course dimension of this association is not clearly understood. We aimed to investigate how affective problems across the life course relate to later-life cognitive state.Methods: Data from 1269 participants from the Medical Research Council National Survey of Health and Development (NSHD, the British 1946 birth cohort) were used. Prospectively-assessed measures of affective symptoms spanning ages 13-69 and categorised into case-level thresholds. Outcomes consisted of a comprehensive measure of cognitive state (Addenbrooke's Cognitive Examination (ACE-III)), verbal memory, and letter search speed and accuracy at age 69.Results: Complementary life course models demonstrated that having 2 or more case-level problems across the life course was most strongly associated with poorer cognitive outcomes, before and after adjusting for sex, childhood cognition, childhood and midlife occupational position and education.Limitations: A disproportionate loss to follow-up of those who had lower childhood cognitive scores may have led to underestimation of the strength of associations.Discussion: Using a population-based prospective study we provide evidence that recurrent lifetime affective problems predicts poorer later-life cognitive state, and this risk can be already manifest in early old age (age 69). Our findings raise the possibility that effective management to minimise affective problems reoccurring across the life course may reduce the associated risk of cognitive impairment and decline. [ABSTRACT FROM AUTHOR]

Background: Among groups of persons living with HIV (PLWH), high-risk drinking trajectories are associated with HIV severity. Whether changes in individuals' alcohol use are associated with changes in HIV severity over the same period is unknown.Methods: Veterans Aging Cohort Study (VACS) data from VA's EHR (2/1/2008-9/30/2016) identified AUDIT-C screens for all PLWH. Pairs of AUDIT-C screens within 9-15 months were included if CD4 and/or viral load (VL) was measured within 9 months after baseline and follow-up AUDIT-Cs. Linear regression assessed change in HIV severity (CD4 and logVL) associated with AUDIT-C change adjusted for confounders. Mean changes in HIV severity were estimated for each AUDIT-C change value. For all measures of change, positive values indicate improvements (lower drinking and improved HIV severity).Results: Among PLWH, 21,999 and 22,143 were eligible for CD4 and VL analyses, respectively. Most had non- or low-level drinking and stable consumption over time (mean AUDIT-C change = .08, SD = 1.91). HIV severity improved over time [mean CD4 change = 20.5 (SD 180.8); mean logVL change = 0.12 (SD 0.71)]. AUDIT-C changes were associated non-linearly with changes in CD4 (p = 0.03) and logVL (p < 0.001). Improvement in HIV severity was greatest among those with stable AUDIT-C scores over time; those with greater AUDIT-C increases fared worse than those with smaller increases in or stable AUDIT-Cs.Conclusions: Improvement in HIV severity was greatest among PLWH with relatively stable drinking, most of whom initially did not drink or drank at low levels. Those with large changes (especially increases) in drinking appear at greatest risk for poor HIV control. [ABSTRACT FROM AUTHOR]

Introduction: While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans.Methods: 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively.Results: Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005).Limitations: Limitations included small sample size and the cross-sectional nature of the data.Conclusions: The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Met's impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk. [ABSTRACT FROM AUTHOR]

Objectives: To explore the ways in which medical abortion pills are obtained and used by university students in Chile in a clandestine context.Study Design: Using a qualitative approach, we conducted in-depth interviews with 30 young women who had had a medical abortion between 2006 and 2016 while attending university. We recorded the details of their pathways to abortion and their experience of abortion, and how they used networks in the university to find the pills and learn how to use them. The interviews were analyzed using narrative content analysis.Results: The findings show that medical abortion did not take place completely outside the healthcare system for these students, who accessed ultrasound scans pre- and post-abortion and post-abortion care. However, even with help and support from contacts, partners and friends, the clandestine situation created uncertainty and fear, which dominated the whole process, from finding and purchasing the pills, to uncertainty about correct doses and whether the abortion was going as it should and was complete or not. There was a high perception that failure and complications might be occurring, which led many of them to seek post-abortion care. The process was very demanding, requiring information, time, privacy to have the abortion, support and resources, and the ability to deal with risk.Conclusions: Medical abortion allowed these young women to have safe abortions in terms of reduced risks to health and autonomy through self-management. However, clandestinity made them physically, socially and emotionally vulnerable and exposed them to the risk of normative, violent judgments during post-abortion care.Implications: Access to medical abortion has transformed the experience of abortion in Chile, where abortion is illegal, because it is possible to use it safely and effectively outside healthcare settings. However, uncertainty, fear and risk will continue to dominate the experience, which can only be transformed by making abortion legal and available. [ABSTRACT FROM AUTHOR]

Background: Identifying clinical correlates associated with reduced suicidal ideation may highlight new avenues for the treatment of suicidal thoughts. Anhedonia occurs across psychiatric diagnoses and has been associated with specific neural circuits in response to rapid-acting treatments, such as ketamine. This analysis sought to evaluate whether reductions in suicidal ideation after ketamine administration were related to reduced levels of anhedonia, independent of depressive symptoms.Methods: This post-hoc analysis included treatment-resistant patients with either major depressive disorder (MDD) or bipolar disorder (BD) from several clinical trials of ketamine. Anhedonia was assessed using a subscale of the Beck Depression Inventory (BDI) and the Snaith-Hamilton Pleasure Scale (SHAPS). The outcome of interest was suicidal ideation, as measured by a subscale of the Scale for Suicide Ideation (SSI5), one day post-ketamine administration.Results: Anhedonia, as measured by the SHAPS, was associated with suicidal thoughts independent of depressive symptoms both before and after ketamine administration. One day post-ketamine administration, improvements on the SHAPS accounted for an additional 13% of the variance in suicidal thought reduction, beyond the influence of depressive symptoms. The BDI anhedonia subscale was not significantly associated with suicidal thoughts after adjusting for depressive symptoms.Limitations: Data were limited to patients experiencing a major depressive episode and may not be generalizable to patients experiencing an active suicidal crisis.Conclusions: Suicidal thoughts may be related to symptoms of anhedonia independent of other depressive symptoms. These results have implications for the potential mechanisms of action of ketamine on suicidal thoughts. [ABSTRACT FROM AUTHOR]

Background Context: Physical therapy is commonly sought by people with lumbar disc herniation and associated radiculopathy. It is unclear whether physical therapy is effective for this population.Purpose: To determine the effectiveness of physical therapist-delivered individualized functional restoration as an adjunct to guideline-based advice in people with lumbar disc herniation and associated radiculopathy.Study Design: This is a preplanned subgroup analysis of a multicenter parallel group randomized controlled trial.Patient Sample: The study included 54 participants with clinical features of radiculopathy (6-week to 6-month duration) and imaging showing a lumbar disc herniation.Outcome Measures: Primary outcomes were activity limitation (Oswestry Disability Index) and separate 0-10 numerical pain rating scales for leg pain and back pain. Measures were taken at baseline and at 5, 10, 26, and 52 weeks.Methods: The participants were randomly allocated to receive either individualized functional restoration incorporating advice (10 sessions) or guideline-based advice alone (2 sessions) over a 10-week period. Treatment was administered by 11 physical therapists at private clinics in Melbourne, Australia.Results: Between-group differences for activity limitation favored the addition of individualized functional restoration to advice alone at 10 weeks (7.7, 95% confidence interval [CI] 0.3-15.1) and 52 weeks (8.2, 95% CI 0.7-15.6), as well as back pain at 10 weeks (1.4, 95% CI 0.2-2.7). There were no significant differences between groups for leg pain at any follow-up. Several secondary outcomes also favored individualized functional restoration over advice.Conclusions: In participants with lumbar disc herniation and associated radiculopathy, an individualized functional restoration program incorporating advice led to greater reduction in activity limitation at 10- and 52-week follow-ups compared with guideline-based advice alone. Although back pain was significantly reduced at 10 weeks with individualized functional restoration, this effect was not maintained at later timepoints, and there were no significant effects on leg pain, relative to guideline-based advice. [ABSTRACT FROM AUTHOR]

Background: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial. Here, we report the results of the secondary endpoint, health-related quality of life (HRQoL), of this trial.Methods: EORTC 18071 was a multinational, double-blind, randomised, phase 3 trial in patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) in 19 countries worldwide. Participants were randomly assigned (1:1) centrally by an interactive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region. HRQoL was assessed with the EORTC QLQ-C30 quality-of-life instrument at baseline, weeks 4, 7, 10, and 24, and every 12 weeks thereafter up to 2 years, irrespective of disease progression. Results were summarised by timepoint and in a longitudinal manner in the intention-to-treat population. Two summary scores were calculated for each HRQoL scale: the average score reported during induction (ipilimumab or placebo at a dose of 10 mg/kg, administered as one single dose at the start of days 1, 22, 43, and 64-ie, four doses in 3 weeks), and the average score reported after induction. A predefined threshold of a 10 point difference between arms was considered clinically relevant. The primary HRQoL endpoint was the global health scale, with the predefined hypothesis of no clinically relevant differences after induction between groups. This trial is registered with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168.Findings: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to treatment: 475 in the ipilimumab group and 476 in the placebo group. Compliance with completing the HRQoL questionnaire was 893 (94%) of 951 patients at baseline, 693 (75%) of 924 at week 24, and 354 (51%) of 697 at week 108. Patient mean global health scores during (77·32 [SD 17·36] vs 72·96 [17·82]; p=0·00011) and after induction (76·48 [17·52] vs 72·32 [18·60]; p=0·00067) were statistically significantly different between groups but were not clinically relevant. Mean global health scores differed most between the groups at week 7 (77 [SD 19] in the placebo group vs 72 [22] in the ipilimumab group) and week 10 (77 [20] vs 70 [23]). Mean HRQoL scores differed by more than 10 points at week 10 between treatment groups for diarrhoea (7·67 [SD 17·05] for placebo vs 18·17 [28·35] for ipilimumab) and insomnia (15·17 [22·53] vs 25·60 [29·19]).Interpretation: Despite increased toxicity, which led to treatment discontinuation for most patients during the induction phase of ipilimumab administration, overall HRQoL, as measured by the EORTC QLQ-C30, was similar between groups, as no clinically relevant differences (10 points or more) in global health status scores were observed during or after induction. Clinically relevant deterioration for some symptoms was observed at week 10, but after induction, no clinically relevant differences remained. Together with the primary analysis, results from this trial show that treatment with ipilimumab results in longer recurrence-free survival compared with that for treatment with placebo, with little impairment in HRQoL despite grade 3-4 investigator-reported adverse events.Funding: Bristol-Myers Squibb. [ABSTRACT FROM AUTHOR]

Background: Despite the known benefits of physical activity (PA) among people with anxiety, little is known about PA levels in people with anxiety at the population level. This study explored the global prevalence of anxiety and its association with PA.Methods: Cross-sectional, community-based data from the World Health Survey was analyzed. Prevalence of anxiety was estimated for 237,964 individuals (47 countries). PA was categorized as low, moderate, and high based on the International Physical Activity Questionnaire (short form). The association between PA and anxiety was assessed by multivariable logistic regression.Results: The overall global prevalence of anxiety was 11.4% (47 countries). Across 38 countries with available data on PA, 62.5%, 20.2%, and 17.3% of the sample engaged in high, moderate, and low levels of PA respectively. The prevalence of low physical activity in those with and without anxiety was 22.9% vs. 16.6% (p<0.001) (38 countries, n=184,920). In the pooled model adjusted for socio-demographics, depression, and country, individuals engaging in low PA (vs. high PA) had 1.32 (95% CI=1.17-1.47) times higher odds for anxiety than those with high PA. Female sex, older age, lower education and wealth, and depression were also associated with low PA. At the individual country level, there was a significant positive association between low PA and anxiety in 17 of the 38 countries.Conclusion: Low PA levels are associated with increased prevalence of anxiety. There is a need for longitudinal research to establish the directionality of the relationships observed. [ABSTRACT FROM AUTHOR]

Introduction: Osteosynthesis of anterior pubic ramus fractures can be challenging, especially in poor bone quality. The aim of the present study was to compare plate and retrograde endomedullary screw fixation of the superior pubic ramus with low bone mineral density (BMD).Materials and Methods: Twelve human cadaveric hemi-pelvises were analyzed in a matched pair study design. BMD of the specimens was 35±30mgHA/cm(3), as measured in the fifth lumbar vertebra. A simulated two-fragment superior pubic ramus fracture model was fixed with either a 7.3-mm cannulated retrograde screw (Group 1) or a 10-hole 3.5-mm reconstruction plate (Group 2). Cyclic progressively increasing axial loading was applied through the acetabulum. Relative interfragmentary movements were captured using an optical motion tracking system.Results: Initial axial construct stiffness was 424±116.1N/mm in Group 1 and 464±69.7N/mm in Group 2, with no significant difference (p=0.345). Displacement and gap angle at the fracture site during cyclic loading were significantly higher in Group 1 compared to Group 2. Cycles to failure, based on clinically relevant criteria, were significantly lower in Group 1 (3469±1837) compared to Group 2 (10,226±3295) (p=0.028). Failure mode in Group 1 was characterized by screw cutting through the cancellous bone. In Group 2 the specimens exclusively failed by plate bending.Conclusions: From biomechanical point of view, pubic ramus stabilization with plate osteosynthesis is superior compared to a single retrograde screw fixation in osteoporotic bone. However, the extensive surgical approach needed for plating must be considered. [ABSTRACT FROM AUTHOR]

Introduction: Implant-related infection is a challenging complication in musculoskeletal trauma surgery. In the present study, we examined the role of implant material and surface topography as influencing factors on the development of infection in an experimental model of plating osteosynthesis in the rabbit.Methods: The implants included in this experimental study were composed of: standard Electropolished Stainless Steel (EPSS), standard titanium (Ti-S), roughened stainless steel (RSS) and surface polished titanium (Ti-P). Construct stability and load-to-failure of Ti-P implants was compared to that of Ti-S implants in a rabbit cadaveric model. In an in vivo study, a rabbit humeral fracture model was used. Each rabbit received one of three Staphylococcus aureus inocula, aimed at determining the infection rate at a low, medium and high dose of bacteria. Outcome measures were quantification of bacteria on the implant and in the surrounding tissues, and determination of the infectious dose 50 (ID50).Results: No significant differences were observed between Ti-S and Ti-P regarding stiffness or failure load in the cadaver study. Of the 72 rabbits eventually included in the in vivo study, 50 developed an infection. The ID50 was found to be: EPSS 3.89×10(3) colony forming units (CFU); RSS 8.23×10(3) CFU; Ti-S 5.66×10(3) CFU; Ti-P 3.41×10(3) CFU. Significantly lower bacterial counts were found on the Ti-S implants samples compared with RSS implants (p<0.001) at the high inoculum. Similarly, lower bacterial counts were found in the bone samples of animals in the Ti-S group in comparison with both RSS and EPSS groups, again at the high inoculation dose (p<0.005).Conclusion: No significant differences were seen in susceptibility to infection when comparing titanium and steel implants with conventional or modified topographies. Ti-P implants, which have previously been shown in preclinical studies to reduce complications associated with tissue adherence, do not affect infection rate in this preclinical fracture model. Therefore, Ti-P implants are not expected to affect the infection rate, or influence implant stability in the clinical situation. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson's disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure is currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson's disease who experience freezing.Methods: Twenty participants with idiopathic Parkinson's disease who experienced freezing during gait but who were able to walk short distances indoors independently were recruited. At least three attempts at gait initiation were recorded using a 10 camera Qualisys motion analysis system and four force platforms. Test conditions were; Laser Cane, sound metronome, vibrating metronome, walking stick and no intervention.Results: During testing 12 of the 20 participants had freezing episodes, from these participants 100 freezing and 91 non-freezing trials were recorded. Clear differences in the movement patterns were seen between freezing and non-freezing episodes. The Laser Cane was most effective cueing device at improving the forwards/backwards and side to side movement and had the least number of freezing episodes. The walking stick also showed significant improvements compared to the other conditions. The vibration metronome appeared to disrupt movement compared to the sound metronome at the same beat frequency.Conclusion: This study identified differences in the movement patterns between freezing episodes and non-freezing episodes, and identified immediate improvements during gait initiation when using the Laser Cane over the other interventions. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in profiling the quality of individual medical providers. Valid assessment of individuals should highlight improvement opportunities, but must be considered in the context of limitations.Study Design: High quality clinical data from the American College of Surgeons NSQIP, gathered in accordance with strict policies and specifications, was used to construct individual surgeon-level assessments. There were 39,976 cases evaluated, performed by 197 surgeons across 9 hospitals. Both 2-level (cases by surgeon) and 3-level (cases by surgeon by hospital) risk-adjusted, hierarchical regression analyses were performed. Outcomes were 30-day postoperative morbidity, surgical site infection, and mortality. Surgeon performance was compared in both absolute and relative terms. "Signal-to-noise" reliability was calculated for surgeons and models. Projected case requirements for reliability levels were generated.Results: Surgeon performances could be distinguished to different degrees: morbidity distinguished best, mortality least. Outliers could be identified for morbidity and infection, but not mortality. Reliability was also highest for morbidity and lowest for mortality. Even models with high overall reliability did not assess all providers reliably. Incorporating institutional effects had predictable effects: penalizing providers at "good" institutions, benefiting providers at "poor" institutions.Conclusions: Individual surgeon profiles can, at times, be distinguished with moderate or good reliability, but to different degrees in different models. Absolute and relative comparisons are feasible. Incorporating institutional level effects in individual provider modeling presents an interesting policy dilemma, appearing to benefit providers at "poor-performing" institutions, but penalizing those at "high-performing" ones. No portrayal of individual medical provider quality should be accepted without consideration of modeling rationale and, critically, reliability. [ABSTRACT FROM AUTHOR]

Aims: To ascertain perceptions of reasons for follow-up after cancer treatment among service users (patients and carers), primary care practitioners and specialist clinicians (doctors and specialist nurses) and to identify levels of preference for different models of follow-up and the effect of an individual’s experience on preferred models. Materials and methods: A national survey designed to meet the needs of each key respondent group was carried out after a structured literature review, an extensive consultation process and a pilot scheme. Respondents were asked to assess their degree of preference for 10 pre-selected indications for follow-up. Eight models of follow-up were also identified and respondents were asked to state their experience and preference for each type. The questionnaire was distributed nationally via the 34 cancer networks in England and was available both online and in hard copy (postal). The uptake for the electronic format was in the main by primary care practitioners and specialist clinicians. Service users preferred the paper (postal) format. The survey was also publicised through the primary care and patient partnership forums at a Cancer Network Development event. Results: In total, 2928 responses were received, comprising service users (21% of the sample), primary care practitioners (32%) and specialist clinicians (47%). Eighty-six per cent of responses were received from the 10 strategic health authorities in England, with the remaining 14% from Scotland, Wales and The Isle of Man. The responses from Scotland, Wales and the Isle of Man generally occurred where they interfaced with English cancer networks or had been engaged through word of mouth by colleagues. Among all respondents the main aims of cancer follow-up were considered to be: (1) to monitor for early complications after treatment; (2) to detect recurrences early; (3) to detect late effects of treatment. The most commonly experienced method of follow-up among all respondent groups was outpatient review with a doctor. This was considered to be the most preferred follow-up option among service users (86%). The least preferred option among service users was postal follow-up (32%). Primary care practitioners and specialist clinicians were more likely than service users to have experienced alternative methods of follow-up, such as telephone follow-up, self-triggered referral and non-specialist follow-up. These models were highly rated by those who had experience of them. Conclusions: There was a reasonable level of consensus between service users, primary care practitioners and specialist clinicians as to the reasons for follow-up. Service users seemed to have higher expectations of follow-up, particularly in relation to detecting recurrences early. As respondents were more likely to prefer a method of follow-up delivery that they had experienced than one they had not; there could be resistance to change from established methods to new methods without adequate explanation. This suggests that the communication of new methods could be critical to their successful introduction. [Copyright &y& Elsevier]

Abstract: This article reports the use of a two-dimensional (2-D) capacitive micro-machined ultrasound transducer (CMUT) to acquire radio-frequency (RF) echo data from relatively large volumes of a simple ultrasound phantom to compare three-dimensional (3-D) elasticity imaging methods. Typical 2-D motion tracking for elasticity image formation was compared with three different methods of 3-D motion tracking, with sum-squared difference (SSD) used as the similarity measure. Differences among the algorithms were the degree to which they tracked elevational motion: not at all (2-D search), planar search, combination of multiple planes and plane independent guided search. The cross-correlation between the predeformation and motion-compensated postdeformation RF echo fields was used to quantify motion tracking accuracy. The lesion contrast-to-noise ratio was used to quantify image quality. Tracking accuracy and strain image quality generally improved with increased tracking sophistication. When used as input for a 3-D modulus reconstruction, high quality 3-D displacement estimates yielded accurate and low noise modulus reconstruction. (E-mail: tgfisher@wisc.edu) [Copyright &y& Elsevier]

Abstract: Ultrasound strain imaging using 2-D speckle tracking has been proposed to quantitatively assess changes in myocardial contractility caused by ischemia. Its performance must be demonstrated in a controlled model system as a step toward routine clinical application. In this study, a well-controlled 2-D cardiac elasticity imaging technique was developed using two coplanar and orthogonal linear probes simultaneously imaging an isolated retroperfused rabbit heart. Acute ischemia was generated by left anterior descending (LAD) artery ligation. An excitation-contraction decoupler, 2,3-butanedione monoxime, was applied at a 4-mM concentration to reversibly reduce myocardial contractility. Results using a single probe demonstrate that directional changes in the in-plane principal deformation axes can help locate the bulging area as a result of LAD ligation, which matched well with corresponding Evans Blue staining, and strains or strain magnitude, based on principal stretches, can characterize heart muscle contractility. These two findings using asymmetric displacement accuracy (i.e., normal single-probe measurements with good axial but poor lateral estimates) were further validated using symmetric displacement accuracy (i.e., dual-probe measurements using only accurate axial tracking estimates from each). However, the accuracy of 2-D cardiac strain imaging using a single probe depends on the probe''s orientation because of the large variance in lateral displacement estimates. (E-mail: cxjia@umich.edu) [Copyright &y& Elsevier]

Purpose: To investigate the clinical use of a commercially available gating system for minimizing respiratory-induced anatomic motion over a range of treatment sites. Methods and Materials: The gating system consists of a reflective marker placed on the patient's anterior surface. The motion of the marker is tracked using a camera interfaced to a computer. Gated intervals were defined that limited the motion of the diaphragm to less than 1 cm during free breathing. Patients underwent a computed tomography virtual simulation using a breath-hold technique. At the time of treatment, verification of patient position and gating interval were performed using electronic portal imaging. Results: Between September 2000 and January 2002, 136 patients were simulated with respiratory gating. Of these, 108 patients were treated to 110 sites for a total of 2301 treatment sessions. Ninety-seven percent of patients completed their entire course of therapy with gated treatment delivery. Conclusions: Respiratory gating is a practical and achievable solution for minimizing respiratory-induced target motion during both simulation and treatment. With proper patient selection and training, it can be successfully implemented in a clinical radiation therapy department. [ABSTRACT FROM AUTHOR]