Search

The real-time quaking-induced conversion (RT-QuIC) alpha-synuclein (aSyn) protein kinetic seeding assay has been very useful for detecting pathological aggregates in various synucleinopathies including Parkinson’s disease (PD). This biomarker assay relies on fresh frozen tissue to effectively seed and amplify aSyn aggregating protein. With vast repositories of formalin-fixed paraffin-embedded (FFPE) tissues, it is paramount to harness the power of kinetic assays to unlock the diagnostic potential of archived FFPE biospecimens. However, the major challenge posed by significantly reduced amplification of formalin-fixed tissues in the assay suggests that formalin fixation deterred monomer interaction with the sample seed and depressed subsequent protein aggregation. To overcome this challenge, we developed a kinetic assay seeding ability recovery (KASAR) protocol to maintain the integrity of the tissue and seeding protein. For this, we implemented a series of heating steps with the brain tissue suspended in a buffer composed of 500 mM tris-HCl (pH 7.5) and 0.02% SDS after the standard deparaffinization of the tissue sections. Initially, samples from seven human brain samples, including four samples from patients diagnosed with dementia with Lewy bodies (DLB) and three samples from healthy controls without DLB, were compared to fresh frozen samples under three different, but clinically common sample storage conditions: formalin-fixed, FFPE, and FFPE slices cut 5 µm thick. The KASAR protocol was able to recover seeding activity for all positive samples in all storage conditions. Next, 28 FFPE samples from the submandibular gland (SMG) of patients diagnosed with PD, incidental Lewy body disease (ILBD), or healthy controls were tested with 93% of results replicating when blinded. With samples of only a few milligrams, this protocol recovered the same quality of seeding in formalin-fixed tissue as fresh frozen tissue. Moving forward, protein aggregate kinetic assays, in conjunction with the KASAR protocol, can be used to understand and diagnose neurodegenerative diseases more comprehensively. Overall, our KASAR protocol unlocks and restores the seeding ability of formalin-fixed paraffin-embedded tissues for the amplification of biomarker protein aggregates in kinetic assays.

Background: In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a.Methods: RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965.Findings: 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5-20.6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1.05 [95% CI 0.90-1.21], p=0.55; absolute difference 0.3% (-5.1 to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.Interpretation: Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial.Funding: UK Medical Research Council. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory viral infections have been associated with an increased incidence of adverse cardiovascular events. However, it is unclear whether severe respiratory viral infections are associated with an increased risk of acute aortic syndromes (AAS). This study was designed to assess whether Coronavirus disease 2019 (COVID-19) and Influenza illnesses are associated with an increased incidence of subsequent AAS in the US population., Methods: We used the MarketScan database (2011-2021) to identify patients 18-99 years of age without prior diagnosis of aortic pathology who were diagnosed with COVID-19 or Influenza. Identified patients were matched 1:1 by age and sex to control patients without COVID-19 or Influenza. The primary outcome was incidence of AAS (dissection, intramural hematoma, penetrating aortic ulcer, or aneurysm rupture) within 180-days of a viral infection. The association between infection and risk of developing an AAS was analyzed using multivariate Cox proportional hazards models., Results: We identified 1,775,698 patients, including 779,229 (44%) with mild COVID-19, 42,141 (2%) with severe COVID-19, and 66,479 (4%) with Influenza that were matched to 887,849 (50%) control patients without COVID-19 or Influenza illnesses. A total of 164 patients experienced AAS within 6-months after diagnosis, which was highest among those after severe COVID-19. The predicted incidence of AAS was significantly higher among patients after severe COVID-19 (14.1 events/100,000 person-years), mild COVID-19 (13.3 events/100,000), and influenza (13.3 events/100,000) when compared to control patients (2.6 events/100,000). In risk-adjusted Cox regression models, severe COVID-19 (HR:5.4, 95% CI:2.8-10.4; P < 0.01), mild COVID-19 (HR:5.1, 95% CI:3.3-7.7; P < 0.01) and influenza (HR:5.1, 95% CI:2.6-9.7; P < 0.01) diagnoses were associated with a significantly increased risk of AAS within 180-days when compared to matched controls., Conclusions: There is an increased risk of developing acute aortic event in the months following illness with Influenza or COVID-19. These data highlight the need to closely monitor at-risk patients following a viral respiratory infection., (Published by Elsevier Inc.)

Objectives: To compare the results of Gleason Grade Group (GGG) classification following central pathology review with previous local pathology assessment, and to examine the difference between using overall and worst GGG in a large patient cohort treated with radiotherapy and short-course hormone therapy., Patients and Methods: Patients with low- to high-risk localized prostate cancer were randomized into the multicentre CHHiP fractionation trial between 2002 and 2011. Patients received short-course hormone therapy (≤6 month) and radical intensity-modulated radiotherapy (IMRT). Of 2749 consented patients, 1875 had adequate diagnostic biopsy tissue for blinded central pathology review. The median follow-up was 9.3 years. Agreement between local pathology and central pathology-derived GGG and between central pathology-derived overall and worst GGG was assessed using kappa (κ) statistics. Multivariate Cox regression and Kaplan-Meier methods were used to compare the biochemical/clinical failure (BCF) and distant metastases (DM) outcomes of patients with GGG 1-5., Results: There was poor agreement between local pathology- and central pathology-derived GGG (κ = 0.19) but good agreement between overall and worst GGG on central pathology review (κ = 0.89). Central pathology-derived GGG stratified BCF and DM outcomes better than local pathology, while overall and worst GGG on central pathology review performed similarly. GGG 3 segregated with GGG 4 for BCF, with BCF-free rates of 90%, 82%, 74%, 71% and 58% for GGGs 1-5, respectively, at 8 years when assessed using overall GGG. There was a progressive decrease in DM-free rates from 98%, 96%, 92%, 88% and 83% for GGGs 1-5, respectively, at 8 years with overall GGG. Patients (n = 57) who were upgraded from GGG 2-3 using worst GS had BCF-free and DM-free rates of 74% and 92% at 8 years. CHHiP eligibility criteria limit the interpretation of these results., Conclusion: Contemporary review of International Society of Urological Pathology GGG successfully stratified patients treated with short-course hormone therapy and IMRT with regard to both BCF-free and DM-free outcomes. Patients upgraded from GGG 2 to GGG 3 using worst biopsy GS segregate with GGG 3 on long-term follow-up. We recommend that both overall and worst GS be used to derive GGG., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database., Methods: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands., Results: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls., Conclusions: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection., Competing Interests: Disclosures None.

Background: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity., Methods: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants., Findings: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm 3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group)., Interpretation: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits., Funding: Cancer Research UK., Competing Interests: Declaration of interests JMB, EMD, ME, CLG, JSH, PH, MAS, JCT, and YT report grants from Cancer Research UK during the conduct of the study. SVL reports PhD funding from Cancer Research UK. JMB reports grants and non-financial support from AstraZeneca, Clovis Oncology, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis (previously GlaxoSmithKline), Pfizer, Puma Biotechnology, and Roche outside the submitted work. CEC reports grants from National Institute for Health Research Efficacy and Mechanism Evaluation, RADNET, the Lancet Breast Cancer Commission, and Addenbrooke's Charitable Trust outside the submitted work. CEC also reports membership of five external independent monitoring committees and is Chair of the Lancet Breast Cancer Commission. AMK is President of the European Society of Radiation Oncology. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Statins are considered standard-of-care medical therapy for patients undergoing lower extremity bypass (LEB) procedures for chronic limb-threatening ischemia (CLTI). It is unclear, however, whether up-titrating and maintaining patients on higher-intensity statin medications following LEB improves limb salvage outcomes. This study was designed to evaluate whether high-intensity statin therapy impacts the risk of amputation and reintervention following LEB for patients with CLTI., Methods: The IBM MarketScan database was used to identify adult patients (18-99 years old) who underwent a LEB for CLTI between 2008 and 2017. Patients lacking insurance covering drug reimbursement or those who already had undergone amputation before time of bypass were excluded. Using pharmacy claims and national drug codes to define statin intensity, patients were stratified into three groups: high-intensity, low-intensity, and limited statin therapy. The association between intensity of statin therapy and need for reintervention and/or major amputation after LEB was analyzed using Kaplan-Meier curves and risk-adjusted Cox proportional hazard models., Results: A total of 25,907 patients who underwent LEB for CLTI were identified, of which 6696 (26%) were maintained on high-dose statins, 9297 (36%) were on low-dose statins, and 9914 (38%) had inconsistent pharmacy claims for statin therapy after surgery. Patients on high-intensity statins were, on average, younger and more likely to be male with comorbid disease (diabetes, hypertension, hyperlipidemia, obesity, renal insufficiency, ischemic heart disease, cerebrovascular disease, and tobacco abuse) than patients on low-intensity statins or limited statin therapy (P < .001 for all comparisons). Following LEB, 6649 patients (25.6%) required a reintervention, and 2550 patients (9.8%) went on to have a major amputation during follow-up. Patients maintained on high-intensity statins after LEB had a significantly lower likelihood of requiring a reintervention (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.45-0.51; P < .001) or amputation (HR, 0.27; 95% CI, 0.24-0.30; P < .001) as compared with patients on limited statin therapy. Further, there was a dose-dependent effect for these outcomes relative to patients on low-intensity statins in risk-adjusted models, and it was independent of whether an autologous vein graft was used for the LEB. Finally, among patients who underwent a reintervention, high-dose statin therapy also significantly reduced the HR for subsequent amputation (HR, 0.21; 95% CI, 0.18-0.25; P < .001)., Conclusions: Patients with CLTI on high-intensity therapy following LEB had a significantly lower risk of requiring subsequent reintervention and amputation when compared with patients on low-intensity statins or with limited statin use. These data suggest that patients with CLTI should be up-titrated and/or maintained on high-intensity statins following revascularization whenever possible., (Published by Elsevier Inc.)

Background: Medical management remains the mainstay of treatment for patients who present with acute Type-B aortic dissections (TBAD). However, it is unclear whether patients maintain adherence to their anti-impulse therapy medication regimen following hospital discharge. This study was designed to evaluate rates and predictors of medication adherence among insured patients treated for acute TBAD., Methods: We used the Truven MarketScan database to identify US patients who presented with an acute TBAD between 2008 to 2017. Patients with continuous health insurance (Commercial or Medicare Part C) for at least 12 months after TBAD diagnosis were stratified by whether they underwent open surgical repair (OPEN), thoracic endovascular aortic repair (TEVAR), or only medication management (MED). Prescriptions for anti-impulse therapy medications were captured and adherence was defined by the medication possession ratio as > 80% fill rate over the follow-up period. Mixed-effects logistic regression models were used to identify predictors for medication adherence., Results: A total of 6,702 patients were identified that underwent treatment for TBAD (3% TEVAR, 9% OPEN, & 74% MED), whereas 14% received no intervention. The overall mean (±SD) rate of adherence to anti-impulse therapy was 72.6% ( ± 26), and varied based on type of TBAD intervention (73.4% TEVAR, 74.4% OPEN, & 72.4% MED). The majority of patients across all treatment groups were prescribed ≥ 2 agents, with beta-blockers and diuretics being the most common medication classes. The odds of adherence to anti-impulse therapy were significantly lower for patients who were female (OR: 0.93; 95%CI:0.85-0.99; P = 0.03), aged < 45 years (OR: 0.81; 95%CI:0.69-0.96; P < 0.001), nonadherent on preexisting therapy (OR: 0.81; 95%CI: 0.73-0.89; P < 0.001), and when medications were obtained in less than a 90 days supply from retail pharmacies., Conclusions: Nearly a quarter of patients were nonadherent with anti-impulse therapy prescribed following an acute TBAD, which was more likely among younger female patients not adherent before their event. Adherence was improved among patients who received their medications by mail and when a > 90 days supply was prescribed. These findings may be used by quality improvement initiatives to improve medication adherence following TBAD and help prevent further complications., (Copyright © 2021. Published by Elsevier Inc.)

Background: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control., Methods: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology., Findings: Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5-60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74-1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen., Conclusion: DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer. The trial is registered: ISRCTN01483375., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.F. reports personal fees and other fees from BMS, outside the submitted work. D.B. reports support from National Institute for Health Research during the conduct of the study. E.H. reports grants from Cancer Research UK, during the conduct of the study, grants from Accuray Inc., grants from Varian Medical Systems Inc., grants and non-financial support from Merck Sharp & Dohme, grants and non-financial support from AstraZeneca, grants from Janssen-Cilag, grants and non-financial support from Bayer Healthcare Pharmaceuticals Inc., grants from Kyowa Hakko UK, grants from Alliance Pharma (previously Cambridge Laboratories) and grants from Aventis Pharma Limited (Sanofi), outside the submitted work. H.M. reports personal fees from Warwickshire Head Neck Clinic Ltd, personal fees from AstraZeneca, personal fees from MSD, Sanofi Pasteur and Merck, grants from GSK Biologicals, MSD, Sanofi Pasteur, Silence Therapeutics, GSK PLC and AstraZeneca and other from Sanofi Pasteur, MSD and Merck, outside the submitted work. K.J.H. reports grants and personal fees from AstraZeneca, personal fees from Amgen, personal fees from BMS, grants and personal fees from Boehringer Ingelheim, grants and personal fees from MSD, personal fees from Merck Serono, personal fees from Pfizer and grants and personal fees from Replimune, outside the submitted work. P.S. reports personal fees from advisory board work for AbbVie and non-financial support from Phillips and Accuray, outside the submitted work. The below mentioned authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article: C.M.N., C.L.G., M.B., V.C., S.F., C.M.W., A.S., N.P., T.G.U., M.S., W.S., M.R., K.W., S.R., E.J., A.C., T.R., C.S., S.A.B., Do.G., A.M., M.E., De.G. and J.P.M., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a marked increase in hospital usage, medical resource scarcity, and rationing of surgical procedures. This has created the need for strategies to triage surgical patients. We have described our experience using the American College of Surgeons (ACS) COVID-19 guidelines for triage of vascular surgery patients in an academic surgery practice., Methods: We used the ACS guidelines as a framework to direct the triage of vascular surgery patients during the COVID-19 pandemic. We retrospectively analyzed the results of this triage during the first month of surgical restriction at our hospital. Patients undergoing surgery were identified by reviewing the operating room schedule. We reviewed the electronic medical records (EMRs) and assigned an ACS category, condition, and tier class to each completed surgery. Surgeries that were postponed during the same period were identified from a prospectively maintained list. We reviewed the EMRs for all postponed surgeries and assigned an ACS category, condition, and tier class to each surgery. We reviewed the EMRs for all postponed procedures to identify any adverse events related to the treatment delay., Results: We performed 69 surgeries in 52 patients during the study period. All surgeries were performed to treat emergent, urgent, or time-sensitive elective diagnoses. Of the 69 surgeries, 47 (68%) were from tier 3 and 22 (32%) from tier 2b. We did not perform any surgeries from tier 1 or 2a. We postponed surgery for 66 patients during the same period, of which 36 (55%) were from tier 1, 22 (33%) from tier 2a, 5 (8%) from tier 2b, and 3 (5%) could not be assigned a tier class. No tier 3 surgeries were postponed. Of the 66 patients, 3 (4.5%) experienced an adverse event that could be attributed to the treatment delay., Conclusions: The ACS triage guidelines provided an effective method to decrease vascular surgical volumes during the COVID-19 pandemic without an increase in patient morbidity. We believe the clinical utility of the guidelines would be strengthened by incorporating the SURGCON/VASCCON (surgical activity condition/vascular activity condition) threat level alert system., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Frailty is a syndrome where the ability to cope with acute physiological stress is compromised, although it is unclear what impact this stress has on long-term outcomes. Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity is a validated method for calculating levels of stress associated with vascular procedures. We designed this study to evaluate the long-term impact of different levels of surgical stress among frail older patients undergoing vascular surgery procedures., Methods: We identified all independently living patients who underwent prospective frailty assessment followed by an elective vascular surgery procedure captured in the Vascular Quality Initiative registry (endovascular abdominal aortic aneurysm [AAA] repair, thoracic endovascular aortic repair, suprainguinal and infrainguinal bypass, peripheral vascular intervention, carotid endarterectomy, and open AAA) at an academic institution between January 2016 and July 2018. Patient- and procedure-level data were obtained from our institutional data warehouse and Vascular Quality Initiative database, and used to calculate Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity scores. The association between frailty and composite outcome of any major complications (surgical site infection; graft thrombectomy; major amputation; adverse cardiac, pulmonary, or neurologic event; acute renal insufficiency; and/or reoperation related to the index procedure), nonhome living status, or death within 1 year after low-, medium-, and high-stress vascular procedures was evaluated using bivariate and logistic regression models., Results: A total of 163 patients were identified (70% male, mean age 67.8 years) who underwent open AAA repair (6%), endovascular AAA repair (21%), thoracic endovascular aortic repair (7%), suprainguinal bypass (5%), infrainguinal bypass (18%), carotid endarterectomy (18%), or peripheral vascular interventions (25%), which included 44 (27%) patients diagnosed with frailty before surgery. Overall, frail patients had significantly higher rates of the 1-year composite outcome (48% frail versus 27% nonfrail; P = 0.012) when compared with nonfrail patients, with a significant dose-dependent effect as the level of stress increased. In comparison, increasing levels of surgical stress had a negligible effect on long-term outcomes among nonfrail patients. The interaction between frailty and high surgical stress was found in adjusted regression models to be a significant predictor of adverse outcomes within 1 year after vascular surgery (odds ratio, 3.3; 95% confidence interval, 1.3-8.6; P < 0.01)., Conclusions: Frail patients who undergo high-stress vascular procedures have a significantly higher rate of complications leading to loss of functional independence and mortality within the year after their surgery. These data suggest that estimates of surgical stress should be incorporated into clinical decision making for frail older patients before and after surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic., Methods: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19., Results: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group)., Conclusions: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

Objective: Arteriovenous fistulas (AVFs) used for hemodialysis commonly undergo multiple percutaneous and open interventions to maintain functional patency, but it is unclear whether this strategy is cost-effective. The aim of this study was to evaluate the clinical effectiveness and cost-effectiveness of performing repeated interventions vs starting a new AVF., Methods: We reviewed all patients with mature radiocephalic, brachiocephalic, and brachiobasilic AVFs at a single academic institution between 2007 and 2015 and assessed the clinical effectiveness of each open and percutaneous intervention to maintain functional patency after the fistula was created. These data were used to parameterize a Markov simulation model to determine the cost-effectiveness for performing an open or percutaneous intervention vs creating an AVF at a new anatomic location. This model compared strategies of creating a new AVF after the first to fourth reintervention within a 1-year time window, with the reference being creation of a new AVF on the fourth reintervention. Costs were measured from Medicare's perspective, and effectiveness was measured as quality-adjusted life-years (QALYs) and time in functional access. Incremental cost-effectiveness ratios (ICERs) were calculated by taking the ratio of the difference in cost and the difference in effectiveness between two strategies., Results: A total of 720 AVFs that were created during the 8-year period reached maturity, and 407 (56%) underwent at least one intervention to maintain functional patency, with the median (interquartile range) time to first reintervention of 12.6 (10-17) months. For the strategies of creating a new AVF after the first versus the fourth reintervention, payer costs ranged from $3519 to $3922 for open procedures and $2134 to $3922 for percutaneous procedures. The ICERs for open interventions on failing AVFs were $357,143/QALY after the first reintervention and $95,876/QALY after the second reintervention. The ICERs for percutaneous interventions on failing AVFs ranged from $1,522,078/QALY after the first reintervention to $443,243/QALY after the third reintervention., Conclusions: Whereas the clinical effectiveness of performing percutaneous interventions on failing AVFs diminishes after each reintervention, they are nevertheless less costly than creating a new AVF. In comparison, our data show that creating a new AVF is cost-effective after the second open reintervention procedure., (Published by Elsevier Inc.)

Objective: Frailty and sarcopenia are related but independent conditions commonly diagnosed in older patients that can be used to assess their ability to tolerate the stress of major vascular surgery. For surgical decision-making, however, it is important to know the prognostic implications associated with each of these conditions. The study was designed to assess the association of frailty and sarcopenia phenotypes with long-term survival of patients undergoing surgical and nonsurgical management of vascular disease., Methods: We retrospectively reviewed all patients presenting to the vascular surgery clinic at an academic hospital between December 2015 and August 2017 who underwent prospective frailty assessment with the Clinical Frailty Scale and who had abdominal computed tomography (CT) scans performed within the preceding 12 months. A single axial CT image at the caudal end of the third lumbar vertebra was assessed to measure cross-sectional areas of skeletal muscle. Sarcopenia was defined by established criteria specific for male and female patients. After patients were stratified by frailty and sarcopenia diagnoses along with comorbidities, the association with all-cause mortality was analyzed by Kaplan-Meier curves and Cox regression models., Results: A total of 415 patients underwent both frailty and sarcopenia assessment, of whom 112 (27%) met sarcopenia criteria alone, 48 (12%) met only frailty criteria, and 56 (13%) met criteria for both phenotypes. There were 199 (48%) controls who met neither criterion. Vascular operations were performed in 167 (40%) patients after frailty and sarcopenia assessment, whereas 248 (60%) patients were managed nonoperatively with median (interquartile range) follow-up after CT imaging of 1.5 (1.1-2.2) years. Patients diagnosed with either phenotype were older (mean, 65 years vs 59 years; P < .001) and more likely to be male (69% vs 54%; P < .001) compared with patients without sarcopenia or frailty. Long-term survival was significantly decreased for patients diagnosed with either frailty alone or frailty and sarcopenia who underwent surgical or nonsurgical management (log-rank, P < .001 for both comparisons). In multivariate regression models, however, frailty was the only independent variable (hazard ratio, 7.7; 95% confidence interval, 3.2-18.7; P < .001) that predicted mortality., Conclusions: Frailty and sarcopenia overlap to varying degrees in patients presenting to vascular surgery clinics and can be used alone or in combination to predict long-term survival of older patients. However, our data indicate that it was only the diagnosis of frailty that was an independent predictor of mortality and had the strongest prognostic significance in patients undergoing both surgical and nonoperative management., (Published by Elsevier Inc.)

Purpose: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers., Methods and Materials: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity., Results: One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group., Conclusions: PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Frailty, a clinical syndrome associated with loss of metabolic reserves, is prevalent among patients who present to vascular surgery clinics for evaluation. The Clinical Frailty Scale (CFS) is a rapid assessment method shown to be highly specific for identifying frail patients. In this study, we sought to evaluate whether the preoperative CFS score could be used to predict loss of independence after major vascular procedures., Methods: We identified all patients living independently at home who were prospectively assessed using the CFS before undergoing an elective major vascular surgery procedure (admitted for >24 hours) at an academic medical center between December 2015 and December 2017. Patient- and procedure-level clinical data were obtained from our institutional Vascular Quality Initiative registry database. The composite outcome of discharge to a nonhome location or 30-day mortality was evaluated using bivariate and multivariate regression models., Results: A total of 134 independent patients were assessed using the CFS before they underwent elective open abdominal aortic aneurysm repair (8%), endovascular aneurysm repair (26%), thoracic endovascular aortic repair (6%), suprainguinal bypass (6%), infrainguinal bypass (16%), carotid endarterectomy (19%), or peripheral vascular intervention (20%). Among 39 (29%) individuals categorized as being frail using the CFS, there was no significant difference in age or American Society of Anesthesiologists physical status compared with nonfrail patients. However, frail patients were significantly more likely to need mobility assistance after surgery (62% frail vs 22% nonfrail; P < .01) and to be discharged to a nonhome location (22% frail vs 6% nonfrail; P = .01) or to die within 30 days after surgery (8% frail vs 0% nonfrail; P < .01). Preoperative frailty was associated with a >12-fold higher risk (odds ratio, 12.1; 95% confidence interval, 2.17-66.96; P < .01) of 30-day mortality or loss of independence, independent of the vascular procedure undertaken., Conclusions: The CFS is a practical tool for assessing preoperative frailty among patients undergoing elective major vascular surgery and can be used to predict likelihood of requiring discharge to a nursing facility or death after surgery. The identification of frail patients before major surgery can help manage postoperative expectations and optimize transitions of care., (Published by Elsevier Inc.)

Importance: Despite the growing popularity of cosmetic procedures, the sociocultural and quality-of-life factors that motivate patients to undergo such procedures are not well understood., Objective: To estimate the relative importance of factors that motivate patients to seek minimally invasive cosmetic procedures., Design, Setting, and Participants: This prospective, multicenter observational study was performed at 2 academic and 11 private dermatology practice sites that represented all US geographic regions. Adult patients presenting for cosmetic consultation or treatment from December 4, 2016, through August 9, 2017, were eligible for participation., Exposures: Participants completed a survey instrument based on a recently developed subjective framework of motivations and a demographic questionnaire., Main Outcomes and Measures: Primary outcomes were the self-reported most common motivations in each quality-of-life category. Secondary outcomes were other frequently reported motivations and those associated with specific procedures., Results: Of 529 eligible patients, 511 agreed to participate, were enrolled, and completed the survey. Typical respondents were female (440 [86.1%]), 45 years or older (286 [56.0%]), white (386 [75.5%]), and college educated (469 [91.8%]) and had previously received at least 2 cosmetic procedures (270 [52.8%]). Apart from motivations pertaining to aesthetic appearance, including the desire for beautiful skin and a youthful, attractive appearance, motives related to physical health, such as preventing worsening of condition or symptoms (253 of 475 [53.3%]), and psychosocial well-being, such as the desire to feel happier and more confident or improve total quality of life (314 of 467 [67.2%]), treat oneself or celebrate (284 of 463 [61.3%]), and look good professionally (261 of 476 [54.8%]) were commonly reported. Motivations related to cost and convenience were rated as less important (68 of 483 [14.1%]). Most motivations were internally generated, designed to please the patients and not others, with patients making the decision to undergo cosmetic procedures themselves and spouses seldom being influential. Patients younger than 45 years were more likely to undertake procedures to prevent aging (54 of 212 [25.5%] vs 42 of 286 [14.7%] among patients ≥45 years; P < .001). Patients seeking certain procedures, such as body contouring (19 of 22 [86.4%]), acne scar treatment (36 of 42 [85.7%]), and tattoo removal (8 of 11 [72.7%]), were more likely to report psychological and emotional motivations., Conclusions and Relevance: This initial prospective, multicenter study comprehensively assessed why patients seek minimally invasive cosmetic procedures. Common reasons included emotional, psychological, and practical motivations in addition to the desire to enhance physical appearance. Differences relative to patient age and procedures sought may need further exploration.

Objective: Arteriovenous (AV) fistulas are the preferred hemodialysis access for patients with end-stage renal disease, although multiple interventions are typically needed to maintain patency. When AV fistulas thrombose, however, there is debate as to whether open thrombectomy should be attempted, particularly for salvage of upper arm fistulas. This study was designed to evaluate outcomes after open thrombectomy of upper arm and forearm AV fistulas compared with AV grafts., Methods: We identified all patients who underwent an open thrombectomy procedure for a thrombosed AV fistula or graft at a single academic medical center between January 2006 and March 2017. The specific type of AV fistula or graft was evaluated, as were the patients' demographics, comorbidities, medications, adjunctive procedures during thrombectomy, and secondary interventions. The primary outcome measures, postintervention primary patency and postintervention secondary patency, were analyzed using Kaplan-Meier curves and Cox regression models for risk adjustment., Results: During the study period, 209 open thrombectomy procedures were performed in 139 patients; 73 (35%) were undertaken in AV fistulas and 136 (65%) in grafts. Patients with upper arm fistulas (n = 52; 54% brachiocephalic, 46% brachiobasilic) and forearm fistulas (n = 16) were more likely to be male but less likely to have cerebrovascular disease or ischemic heart disease and to be receiving anticoagulation therapy compared with graft patients. After thrombectomy, the majority of patients underwent dialysis successfully (70% upper arm fistulas, 56% forearm fistulas, 63% grafts; P > .05), and 1-year survival rates were similar in all three cohorts. Postintervention primary patency at 1 year was significantly higher for AV fistulas vs grafts (33% for upper arm fistulas and 25% for forearm fistulas vs 9% for grafts; P < .05), which was confirmed in multivariate analysis, where upper arm AV fistulas had a 46% lower risk of recurrent thrombosis or secondary intervention (hazard ratio, 0.56; 95% confidence interval, 0.35-0.85; P < .05). Postintervention secondary patency at 1 year was similar between AV fistulas and grafts (44% for upper arm fistulas vs 43% for forearm fistulas vs 31% for grafts; P = .16), but in multivariate analysis, upper arm fistulas were significantly less likely to fail (hazard ratio, 0.63; 95% confidence interval, 0.40-1.00; P = .05)., Conclusions: Our data suggest that AV fistula thrombectomy is successful in up to 70% of cases, with significantly improved risk-adjusted 1-year primary and secondary patency rates for upper arm fistulas compared with grafts. Whereas the risk of access failure is high after thrombectomy, efforts to salvage upper arm AV fistulas are effective in most patients and should be undertaken when feasible., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner. We show that lysophosphatidic acid receptor 1 (LPAR1) is accumulated in primary cilia. LPAR1 signaling through Gα12/Gαq was previously reported to be responsible for cancer cell proliferation. We found that in ciliated cells, Gα12 and Gαq are excluded from the cilium, creating a barrier against unlimited proliferation, one of the hallmarks of cancer. Upon loss of primary cilia, LPAR1 redistributes to the plasma membrane with a concomitant increase in LPAR1 association with Gα12 and Gαq. Inhibition of LPA signaling with the small molecule compound Ki16425 in deciliated highly proliferative astrocytes or glioblastoma patient-derived cells/xenografts drastically suppresses their growth both in vitro and in vivo. Moreover, Ki16425 brain delivery via PEG-PLGA nanoparticles inhibited tumor progression in an intracranial glioblastoma PDX model. Overall, our findings establish a novel mechanism by which primary cilium restricts proliferation and indicate that loss of primary cilia is sufficient to increase mitogenic signaling, and is important for the maintenance of a highly proliferative phenotype. Clinical application of LPA inhibitors may prove beneficial to restrict glioblastoma growth and ensure local control of disease.

Objective: Basilic vein transposition (BVT) fistulas may be performed as either a one-stage or two-stage operation, although there is debate as to which technique is superior. This study was designed to evaluate the comparative clinical efficacy and cost-effectiveness of one-stage vs two-stage BVT., Methods: We identified all patients at a single large academic hospital who had undergone creation of either a one-stage or two-stage BVT between January 2007 and January 2015. Data evaluated included patient demographics, comorbidities, medication use, reasons for abandonment, and interventions performed to maintain patency. Costs were derived from the literature, and effectiveness was expressed in quality-adjusted life-years (QALYs). We analyzed primary and secondary functional patency outcomes as well as survival during follow-up between one-stage and two-stage BVT procedures using multivariate Cox proportional hazards models and Kaplan-Meier analysis with log-rank tests. The incremental cost-effectiveness ratio was used to determine cost savings., Results: We identified 131 patients in whom 57 (44%) one-stage BVT and 74 (56%) two-stage BVT fistulas were created among 8 different vascular surgeons during the study period that each performed both procedures. There was no significant difference in the mean age, male gender, white race, diabetes, coronary disease, or medication profile among patients undergoing one- vs two-stage BVT. After fistula transposition, the median follow-up time was 8.3 months (interquartile range, 3-21 months). Primary patency rates of one-stage BVT were 56% at 12-month follow-up, whereas primary patency rates of two-stage BVT were 72% at 12-month follow-up. Patients undergoing two-stage BVT also had significantly higher rates of secondary functional patency at 12 months (57% for one-stage BVT vs 80% for two-stage BVT) and 24 months (44% for one-stage BVT vs 73% for two-stage BVT) of follow-up (P < .001 using log-rank test). However, there was no significant difference between groups in use of interventions (58% for one-stage BVT vs 51% for two-stage BVT; P = .5) to maintain patency. These findings were confirmed in multivariate analysis, in which two-stage BVTs were associated with a significantly lower rate of failure (hazard ratio, 0.39; 95% confidence interval, 0.2-0.8; P < .05) than one-stage BVTs after controlling for confounding variables. Finally, the two-stage BVT was more cost-effective (3.74 QALYs for two-stage BVT vs 3.32 QALYs for one-stage BVT) during 5 years, with an incremental cost-effectiveness ratio of $4681 per QALY., Conclusions: Our data show that two-stage BVTs are more durable and cost-effective than one-stage procedures, with significantly higher patency and lower rates of failure among comparable risk-stratified patients. These findings suggest that additional upfront costs and resources associated with creating two-stage BVTs are justified by their long-term outcomes., (Published by Elsevier Inc.)

Background: Increasing diversity in clinical trials may be worthwhile. We examined clinical trials that restricted eligibility to a single race or ethnicity., Methods: We reviewed 19,246 trials registered on ClinicalTrials.gov through January 2013. We mapped trial ZIP-codes to U.S. Census and American Community Survey data. The outcome was whether trials required participants to be from a single racial or ethnic group., Results: In adjusted analyses, the odds of trials restricting eligibility to a single race/ethnicity increased by 4% per year (95% CI 1.01-1.08, p = .024). Behavioral (5.79% with single race/ethnicity requirements), skin-related (4.49%), and Vitamin D (6.14%) studies had higher rates of single race/ethnicity requirements. Many other trial-specific characteristics, such as funding agency and region of the U.S. in which the trial opened, were associated with eligibility restrictions. In terms of neighborhood characteristics, studies with single race eligibility requirements were more likely to be located in ZIP-codes with greater percentages of those self-reporting the characteristic. For example, 35.2% (SD = 24.9%) of the population self-reported themselves as Black or African American in ZIP-codes with trials requiring participants to be Black/African American, but only 5.9% (SD = 6.9%) self-reported themselves as Black/African American in ZIP-codes with trials that required Asian ethnicity. In ZIP-codes with trials requiring Asian ethnicity, 24.6% (SD = 16.2%) self-reported as Asian. In ZIP-codes with trials requiring Hispanic/Latino ethnicity, 33.3% (SD = 28.5%) self-reported as Hispanic/Latino. Neighborhood level poverty rates and reduced English language ability were also associated with more single race eligibility requirements., Conclusions: In selected fields, there has been a modest temporal increase in single race/ethnicity inclusion requirements. Some studies may not fall under regulatory purview and hence may be less likely to include diverse samples. Conversely, some eligibility requirements may be related to health disparities research. Future work should examine whether targeted enrollment criteria facilitates development of personalized medicine or reduces trial access.

Background: Frailty assessment can help vascular surgeons predict perioperative risk and long-term mortality for their patients. Unfortunately, comprehensive frailty assessments take too long to integrate into clinic workflow. This study was designed to evaluate 2 rapid methods for assessing frailty during vascular clinics-a short patient-reported survey and a provider-reported frailty scale., Methods: We prospectively enrolled 159 patients presenting to an academic medical center vascular surgery clinic between May and November 2016. Patients underwent frailty assessment using 2 rapid methods: (1) the Frail Nondisabled (FiND) survey (5 questions) and (2) the Clinical Frailty Scale (CFS; 9-point scale from robust to severely frail). These were followed by administering the Fried Index, a validated frailty assessment method with 5 measures (weight loss, exhaustion, grip strength, walking speed, and activity level). The correlation between Fried scores (reference standard) with frailty diagnoses derived from FiND and CFS was analyzed using the Spearman-rank test, Cohen's kappa, sensitivity/specificity tests, and receiver operating curves., Results: The evaluated cohort included 87 (55%) females, a mean age of 61 years, 126 (79%) preoperative patients, and 32 (20%) categorized as frail using the Fried Index criteria. The FiND survey was very sensitive (91%) but less specific for diagnosing frailty. In comparison, the CFS was highly specific (96%) for diagnosing frailty and exhibited high inter-rater reliability between surgeon and medical assistant scores (kappa: 0.79; 95% CI: 0.72-0.87; P < 0.001). There was moderate correlation between frailty assigned using the Fried Index and the CFS (rho: 0.41-0.44)., Conclusions: Frailty can be quickly and effectively assessed during vascular surgery clinic using a combination of patient-reported (FiND) and provider-reported (CFS) methods to improve diagnostic accuracy. Implementing routine frailty assessment into clinic workflow can be a valuable tool for risk prediction and surgical decision-making., (Published by Elsevier Inc.)

Background: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy., Methods: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634., Findings: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7-83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5-2·3) of patients in the control group, 0·2% (0·02-1·2) in the reduced-dose group, and 0·5% (0·2-1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were -0·73% (-0·99 to 0·22) for the reduced-dose and -0·38% (-0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and p<0·0001 for partial-breast]) compared with whole-breast radiotherapy., Interpretation: We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide., Funding: Cancer Research UK., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Randomized trials support carotid endarterectomy (CEA) in asymptomatic patients with ≥60% internal carotid artery (ICA) stenosis. The widely referenced Society for Radiologists in Ultrasound Consensus Statement on carotid duplex ultrasound (CDUS) imaging indicates that an ICA peak systolic velocity (PSV) ≥230 cm/s corresponds to a ≥70% ICA stenosis, leading to the potential conclusion that asymptomatic patients with an ICA PSV ≥230 cm/s would benefit from CEA. Our goal was to determine the natural history stroke risk of asymptomatic patients who might have undergone CEA based on consensus statement PSV of ≥230 cm/s but instead were treated medically based on more conservative CDUS imaging criteria., Methods: All patients who underwent CDUS imaging at our institution during 2009 were retrospectively reviewed. The year 2009 was chosen to ensure extended follow-up. Asymptomatic patients were included if their ICA PSV was ≥230 cm/s but less than what our laboratory considers a ≥80% stenosis by CDUS imaging (PSV ≥430 cm/s, end-diastolic velocity ≥151 cm/s, or ICA/common carotid artery PSV ratio ≥7.5). Study end points included freedom from transient ischemic attack (TIA), freedom from any stroke, freedom from carotid-etiology stroke, and freedom from revascularization., Results: Criteria for review were met by 327 patients. Mean follow-up was 4.3 years, with 85% of patients having >3-year follow-up. Four unheralded strokes occurred during follow-up at <1, 17, 25, and 30 months that were potentially attributable to the index carotid artery. Ipsilateral TIA occurred in 17 patients. An additional 12 strokes occurred that appeared unrelated to ipsilateral carotid disease, including hemorrhagic events, contralateral, and cerebellar strokes. Revascularization was undertaken in 59 patients, 1 for stroke, 12 for TIA, and 46 for asymptomatic disease. Actuarial freedom from carotid-etiology stroke was 99.7%, 98.4%, and 98.4% at 1, 3, and 5 years, respectively. Freedom from TIA was 98%, 96%, and 95%, freedom from any stroke was 99%, 96%, and 93%, and freedom from revascularization was 95%, 86%, and 81% at 1, 3, and 5 years, respectively., Conclusions: Patients with intermediate asymptomatic carotid stenosis (ICA PSV 230-429 cm/s) do well with medical therapy when carefully monitored and intervened upon using conservative CDUS criteria. Furthermore, a substantial number of patients would undergo unnecessary CEA if consensus statement CDUS thresholds are used to recommend surgery. Current velocity threshold recommendations should be re-evaluated, with potentially important implications for upcoming clinical trials., (Published by Elsevier Inc.)

Objective: The purpose of this UK study was to evaluate interfraction reproducibility and body image score when using ultraviolet (UV) tattoos (not visible in ambient lighting) for external references during breast/chest wall radiotherapy and compare with conventional dark ink., Methods: In this non-blinded, single-centre, parallel group, randomized control trial, patients were allocated to receive either conventional dark ink or UV ink tattoos using computer-generated random blocks. Participant assignment was not masked. Systematic (∑) and random (σ) setup errors were determined using electronic portal images. Body image questionnaires were completed at pre-treatment, 1 month and 6 months to determine the impact of tattoo type on body image. The primary end point was to determine that UV tattoo random error (σ setup ) was no less accurate than with conventional dark ink tattoos, i.e. <2.8 mm., Results: 46 patients were randomized to receive conventional dark or UV ink tattoos. 45 patients completed treatment (UV: n = 23, dark: n = 22). σ setup for the UV tattoo group was <2.8 mm in the u and v directions (p = 0.001 and p = 0.009, respectively). A larger proportion of patients reported improvement in body image score in the UV tattoo group compared with the dark ink group at 1 month [56% (13/23) vs 14% (3/22), respectively] and 6 months [52% (11/21) vs 38% (8/21), respectively]., Conclusion: UV tattoos were associated with interfraction setup reproducibility comparable with conventional dark ink. Patients reported a more favourable change in body image score up to 6 months following treatment. Advances in knowledge: This study is the first to evaluate UV tattoo external references in a randomized control trial.

Background: Randomised controlled trials (RCTs) often fail to recruit sufficient participants, despite altruism being cited as their motivation. Previous investigations of factors influencing participation decisions have been methodologically limited. This study evaluated how women weigh up different motivations after initially expressing altruism, and explored their understanding of a trial and its alternatives. The trial was the 'Quality of Life after Mastectomy and Breast Reconstruction' (QUEST) trial., Methods: Thirty-nine women participated in qualitative interviews 1 month post-surgery. Twenty-seven women (10 trial decliners and 17 acceptors) who spontaneously mentioned 'altruism' were selected for thematic analysis. Verbatim transcripts were coded independently by two researchers. Participants' motivations to accept or decline randomisation were cross-referenced with their understanding of the QUEST trials and the process of randomisation., Results: The seven emerging themes were: (1) altruism expressed by acceptors and decliners; (2) overriding personal needs in decliners; (3) pure altruism in acceptors; (4) 'hypothetical altruism' amongst acceptors; (5) weak altruism amongst acceptors; (6) conditional altruism amongst acceptors; and (7) sense of duty to participate. Poor understanding of the trial rationale and its implications was also evident., Conclusions: Altruism was a motivating factor for participation in the QUEST randomised controlled trials where the main outcomes comprised quality of life and allocated treatments comprised established surgical procedures. Women's decisions were influenced by their understanding of the trial. Both acceptors and decliners of the trial expressed 'altruism', but most acceptors lacked an obvious treatment preference, hoped for personal benefits regarding a treatment allocation, or did not articulate complete understanding of the trial., Trial Registration: QUEST A, ISRCTN38846532 ; Date assigned 6 January 2010. QUEST B, ISRCTN92581226 ; Date assigned 6 January 2010.

Background and Purpose: FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions., Material and Methods: Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were graded using RTOG (first substudy) and CTCAE criteria v4.03 (second substudy) weekly during treatment and for 4weeks after treatment ended. Primary endpoint was the proportion of patients within each treatment group with grade ⩾3 toxicity (RTOG and CTCAE, respectively) at any time from the start of radiotherapy to 4weeks after completion., Results: 190 and 162 patients were recruited. In the first substudy, evaluable patients with grade 3 RTOG toxicity were: 40Gy/15F 6/44 (13.6%); 27Gy/5F 5/51 (9.8%); 26Gy/5F 3/52 (5.8%). In the second substudy, evaluable patients with grade 3 CTCAE toxicity were: 40Gy/15F 0/43; 27Gy/5F 1/41 (2.4%); 26Gy/5F 0/53., Conclusions: Acute breast skin reactions with two 1-week schedules of whole breast radiotherapy under test in FAST-Forward were mild., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background/aims: Diverse samples in clinical trials can make findings more generalizable. We sought to characterize the prevalence of clinical trials in the United States that required English fluency for participants to enroll in the trial., Methods: We randomly chose over 10,000 clinical trial protocols registered with ClinicalTrials.gov and examined the inclusion and exclusion criteria of the trials. We compared the relationship of clinical trial characteristics with English fluency inclusion requirements. We merged the ClinicalTrials.gov data with US Census and American Community Survey data to investigate the association of English-language restrictions with ZIP-code-level demographic characteristics of participating institutions. We used Chi-squared tests, t-tests, and logistic regression models for analyses., Results: English fluency requirements have been increasing over time, from 1.7% of trials having such requirements before 2000 to 9.0% after 2010 (p < 0.001 from Chi-squared test). Industry-sponsored trials had low rates of English fluency requirements (1.8%), while behavioral trials had high rates (28.4%). Trials opening in the Northeast of the United States had the highest regional English requirement rates (10.7%), while trials opening in more than one region had the lowest (3.3%, p<0.001). Since 1995, trials opening in ZIP codes with larger Hispanic populations were less likely to have English fluency requirements (odds ratio=0.92 for each 10% increase in proportion of Hispanics, 95% confidence interval=0.86-0.98, p=0.013). Trials opening in ZIP codes with more residents self-identifying as Black/African American (odds ratio=1.87, 95% confidence interval=1.36-2.58, p<0.001 for restricted cubic spline term) or Asian (odds ratio=1.16 for linear term, 95% confidence interval=1.07-1.25, p<0.001) were more likely to have English fluency requirements. ZIP codes with higher poverty rates had trials with more English-language restrictions (odds ratio=1.06 for a 10% poverty rate increase, 95% confidence interval=1.001-1.11, p=0.045). There was a statistically significant interaction between year and intervention type, such that the increase in English fluency requirements was more common for some interventions than for others., Conclusion: The proportion of clinical trials registered with ClinicalTrials.gov that have English fluency requirements for study inclusion has been increasing over time. English-language restrictions are associated with a number of characteristics, including the demographic characteristics of communities in which the sponsoring institutions are located., (© The Author(s) 2015.)

Purpose: To determine outcomes of aneurysmal common iliac arteries (aCIA) used for landing zones (LZs) during endovascular aneurysm repair (EVAR)., Methods: This single-center study retrospectively compared 57 EVAR patients (mean age 72±8 years; 56 men) with 70 aCIAs (diameter ≥20 mm) to 25 control EVAR subjects (mean age 73±7 years; 20 men) with 50 normal (≤15-mm) CIA LZs treated consecutively during the same time interval. The CIA LZ measurements were analyzed using random effects linear mixed models to determine diameter change over time. Life tables were used to estimate freedom from endoleak, reintervention, and all-cause mortality., Results: The mean maximum preoperative CIA diameter in the aCIA LZ group was 24.8±4.5 mm (range 20.0-47.3, median 23.9) vs 13.6±1.5 mm (range 9.2-15.0, median 13.9; p<0.001) in the controls. Nineteen aCIA LZs were treated outside the instructions for use of the device. Median follow-up in the aCIAs LZ cohort was 39.2 months [interquartile range (IQR) 15, 61] vs 49.3 months (IQR 36, 61) in the controls (p=0.06). The rate of aCIA LZ change (0.09 mm/mo, 95% CI 0.07 to 0.1) was significantly greater than controls (0.03 mm/mo, 95% CI -0.009 to 0.07; p<0.0001). No type Ib endoleaks developed in either group; however, aCIA LZ patients had 6 (11%) iliac limb-related reinterventions. There were significantly more endograft-related reinterventions in the aCIA LZ patients (n=10, 14%) compared with controls (n=2, 4%; p=0.06). There was no difference in mortality or freedom from any post-hospital discharge endoleak., Conclusion: Aneurysmal CIA LZs used during EVAR experience greater dilatation compared with normal LZs, but no significant difference in outcome was noted in midterm follow-up. However, an increased incidence of graft limb complications or endograft-related reintervention may be encountered. Use of aCIA LZs appears to be safe; however, greater patient numbers and longer follow-up are needed to understand the clinical implications of morphologic changes in these vessels when used during EVAR., (© The Author(s) 2015.)

Background: Barriers to employment in the civilian labor force are increasingly difficult problems for returning veterans with disabilities. Reduced self-perception of disability status because of predominant military norms can be particularly harmful to reintegration efforts., Objective: We analyze rates of self-identified and externally determined disability status among U.S. veterans. Evidence of a lower self-report rate would confirm the hypothesis that armed forces culture might hold back truly deserving veterans from seeking the benefits owed, including specialized employment training programs., Methods: We use data from the Current Population Survey Veterans Supplement over the sample period 1995-2010 on disability status and associated demographic characteristics to present descriptive measures and limited statistical inference., Results: Over the entire sample period, federal agencies considered 29% of the survey respondents to have a service-connected disability versus a 9% self-identification rate. The rate of more severe service-connected disabilities has risen steadily, while less drastic disability rates have fallen. Non-white respondents and those with lower education levels were less likely to self-identify., Conclusions: Large disparities in internal and external disability status identification raise questions about targeting soldiers re-entering the labor force. Employment policy should focus on overcoming negative cultural stereotypes and encouraging self-identification.

Much empirical analysis has documented racial disparities at the beginning and end stages of a criminal case. However, our understanding about the perpetuation of - and even corrections for - differential outcomes as the process unfolds remains less than complete. This Article provides a comprehensive examination of criminal dispositions using all DWI cases in North Carolina during the period 2001-2011, focusing on several major decision points in the process. Starting with pretrial hearings and culminating in sentencing results, we track differences in outcomes by race and gender. Before sentencing, significant gaps emerge in the severity of pretrial release conditions that disadvantage black and Hispanic defendants. Yet when prosecutors decide whether to pursue charges, we observe an initial correction mechanism: Hispanic men are almost two-thirds more likely to have those charges dropped relative to white men. Although few cases survive after the plea bargaining stage, a second correction mechanism arises: Hispanic men are substantially less likely to receive harsher sentences and are sent to jail for significantly less time relative to white men. The first mechanism is based in part on prosecutors' reviewing the strength of the evidence but much more on declining to invest scarce resources in the pursuit of defendants who fail to appear for trial. The second mechanism seems to follow more directly from judicial discretion to reverse decisions made by law enforcement. We discuss possible explanations for these novel empirical results and review methods for more precisely identifying causal mechanisms in criminal justice.

Background: Cediranib is a potent oral vascular endothelial growth factor (VEGF) signalling inhibitor with activity against all three VEGF receptors. The International Collaboration for Ovarian Neoplasia 6 (ICON6) trial was initiated based on evidence of single-agent activity in ovarian cancer with acceptable toxicity., Methods: The ICON6 trial is a 3-arm, 3-stage, double-blind, placebo-controlled randomised trial in first relapse of platinum-sensitive ovarian cancer. Patients are randomised (2 : 3 : 3) to receive six cycles of carboplatin (AUC5/6) plus paclitaxel (175 mg m(-2)) with either placebo (reference), cediranib 20 mg per day, followed by placebo (concurrent), or cediranib 20 mg per day, followed by cediranib (concurrent plus maintenance). Cediranib or placebo was continued for 18 months or until disease progression. The primary outcome measure for stage I was safety, and the blinded results are presented here., Results: Sixty patients were included in the stage I analysis. A total of 53 patients had received three cycles of chemotherapy and 42 patients had completed six cycles. In all, 19 out of 60 patients discontinued cediranib or placebo during chemotherapy because of adverse events/intercurrent illness (n=9); disease progression (n=1); death (n=3); patient decision (n=1); administrative reasons (n=1); and multiple reasons (n=4). Grade 3 and 4 toxicity was experienced by 30 (50%) and 3 (5%) patients, respectively. No gastrointestinal perforations were observed., Conclusion: The addition of cediranib to platinum-based chemotherapy is sufficiently well tolerated to expand the ICON6 trial and progress to stage II.

Background: Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer. In the MRC OV05/EORTC 55955 collaborative trial, we aimed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence., Methods: Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this randomised controlled trial. Clinical examination and CA125 measurement were done every 3 months. Patients and investigators were masked to CA125 results, which were monitored by coordinating centres. If CA125 concentration exceeded twice the upper limit of normal, patients were randomly assigned (1:1) by minimisation to early or delayed chemotherapy. Patients and clinical sites were informed of allocation to early treatment, and treatment was started as soon as possible within 28 days of the increased CA125 measurement. Patients assigned to delayed treatment continued masked CA125 measurements, with treatment commencing at clinical or symptomatic relapse. All patients were treated according to standard local practice. The primary outcome was overall survival. Analysis was by intention to treat. This study is registered, ISRCTN87786644., Findings: 1442 patients were registered for the trial, of whom 529 were randomly assigned to treatment groups and were included in our analysis (265 early, 264 delayed). With a median follow-up of 56·9 months (IQR 37·4-81·8) from randomisation and 370 deaths (186 early, 184 delayed), there was no evidence of a difference in overall survival between early and delayed treatment (HR 0·98, 95% CI 0·80-1·20, p=0·85). Median survival from randomisation was 25·7 months (95% CI 23·0-27·9) for patients on early treatment and 27·1 months (22·8-30·9) for those on delayed treatment., Interpretation: Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone, and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven., Funding: UK Medical Research Council and the European Organisation for Research and Treatment of Cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Twelve young bulls and 12 steers were slaughtered and the carcasses were fabricated at 48 h postmortem. Top rounds, bottom rounds, and rib eyes were vacuum-packaged and stored at 0 degrees C until 21 d postmortem. After subprimal storage, steaks were removed from each cut and displayed under simulated retail conditions for 3 d. Consumer panelists (n = 110) showed little difference in buying preference for top round, bottom round, and rib eye steaks from steers vs bullocks. Also, consumer panelists could not detect color differences between steaks from steers and bullocks. Experienced panelists (n = 6) detected brighter (P less than .05) muscle color for top round and rib eye steaks from steers but detected no difference in muscle color of bottom round steaks from bullocks and steers. Generally, overall desirability scores favored steaks from steer carcasses. This was particularly true of rib eye steaks. Sex-class of carcass did not affect aerobic plate counts of top round, bottom round, or rib eye steaks either before or after 3 d of retail display. Muscle pH was lower for top round and rib eye steaks from steer carcasses; however, the magnitude of this difference was not large enough to affect retail display stability. Muscle pH of bottom round steaks was not affected by sex-class. Although experienced panelists could detect differences in visual appearance of beef retail cuts from steers and bullocks, consumer panelists did not show a clear purchase preference for steer vs bullock beef. These data suggest that beef retail cuts from bullocks are acceptable in visual appearance.

One side, randomly selected from each of 33 carcasses from forage-fed steers, was electrically stimulated within 30 min of exsanguination and hot-bonded (ESHB). Opposite sides were not electrically stimulated and were cold-boned (NESCB) following a 24 h chill (0°C). From 17 ESHB sides, portions of the longissimus dorsi (LD) and semimembranosus (SM) muscles were removed and immediately vacuum packaged. LD and SM muscles were removed from the remaining 16 ESHB sides, wrapped in polyvinyl chloride film, chilled (0°C) for 22 h and then vacuum packaged. LD and SM muscles from NESCB sides (n = 33) were removed and the vacuum packed at 24 h post mortem. Whole muscle characteristics were evaluated initially and after storage periods of 7, 14 or 21 days and steaks were displayesd for 5 years thereafter. Neither hot versus cold-boning nor storage for 21 days affected retail display characteristics of LD and SM steaks (P > 0·05). As retail display time increased, retail lean color, fat color and overall appearance scores decreased., (Copyright © 1992. Published by Elsevier Ltd.)

The effects of electrical stimulation on palatability of hot-boned, pre-rigor and cold-boned, post-rigor frozen beef roasts were studied by use of 16 steer carcasses. Both sides of 8 carcasses were electrically stimulated (1.5 amps; 100 - 1 s impulses); sides from the other 8 carcasses served as controls. One side of each carcass was hot-boned and the remaining side was boned following a 48 h chill (2 C). Roasts from the rump portion (anterior one-fourth) of the biceps femoris muscle were vacuum-packaged and frozen (-20 C). Following a 48-h thaw (0 C). roasts were weighed, measured for length, width and depth, seasoned, placed in cooking bags and roasted to 62.5 C. Cooking losses were less (P<0.06) for hot-boned, pre-rigor frozen vs. cold-boned, post-rigor frozen roasts. Raw pH (post-freezing) was lower (P<0.01) for hot-boned than cold-boned roasts. No differences (P>0.05) were noted in shape changes for stimulation or chilling. Using triangle tests, untrained panel members were able to distinguish controls from electrically stimulated roasts and hot-boned from cold-boned roasts when served as thick (1.27 cm) or thin (2 mm) samples. Thick and thin samples of cold-boned roasts were preferred over hot-boned roasts. For roasts from carcasses that were not electrically stimulated, 62.6% preferred cold-boned roasts for thick samples while 61.4% preferred cold-boned roasts for thin samples. Cold-boned roasts from electrically stimulated carcasses were preferred over hot-boned roasts, 56.5% (thick) vs. 51.5% (thin). Warner-Bratzler shear force results indicated that hot-boned, control roasts required 79% more shear force than cold-boned roasts, but roasts from electrically stimulated carcasses required 14% more force to shear hot-boned than cold-boned roasts.

Fifteen slaughter cattle from five groups (Charolais crossbred bulls, Brahman crossbred steers, Holstein steers, mixed-Exotic crossbred heifers and Hereford-Angus crossbred steers) were randomly selected from a commercial feedlot. Time-on-feed was 108, 114, 102, 108 and 145 days for the aforementioned groups, respectively. Carcasses from Charolais crossbred bulls had the highest percentage yield of chuck and round, but the lowest percentage yield of loin; hereford-Angus crossbred steers had the lowest percentage yield of round and Holstein steers had the lowest percentage yield of rib. Carcasses from Charolais crossbred bulls had the highest percentage yield of major retail-ready subprimals and lean trim, Hereford-Angus crossbred steers had the highest percentage yield of fat trim and Holstein steers had the highest percentage yield of bone from the major wholesale cuts. Mean percentage yields of closely trimmed, boneless retail cuts were highest for carcasses from the bulls and lowest for carcasses from the Hereford-Angus steers. Although Holstein steer carcasses had less fat trim than Brahman-crossbred steers mixed-Exotic heifers, this advantage was largely offset by their higher percentage of bone. Loin steaks from carcasses of Charolais crossbred bulls, Holstein, mixed-Exotic heifers were comparable (P > 0·05)with those of Hereford-Angus steers for shear force and sensory panel tenderness ratings. However, loin steaks from carcasses of Brahman-crossbred steers had significantly higher (P < 0·05) shear force values (least tender) and lower (P < 0·05) tenderness and overall palatability ratings. No diffeerences (P > 0·05) were found for flavor desirability of loin steaks among any of the groups. For bottom round steaks, Hereford-Angus steers received the highest palatability ratings while those from Holstein steers received the lowest palatability ratings., (Copyright © 1985. Published by Elsevier Ltd.)

To conduct laboratory studies in unsedated animals that were similar anatomically and physiologically to man, five full term baboons (four Papio cynocephalus anubis, one Papio cynocephalus cynocephalus) were hand-reared. These infants were used as unsedated animal models in short-term lung clearance studies conducted from birth to 2 years of age. The hand-rearing techniques described here encouraged the formation of an infant-human rearer bond that permitted us to control the level of expressed aggressive behavior as the infant matured. These techniques resulted in baboons which displayed subordinate behavior, showed positive reception to human contact (without evidence of negative stereotypic behavioral anomalies) and remained cooperative subjects for our investigations of short-term pulmonary clearance. The baboons generally were above average in weight in comparison to conspecifically-reared baboons of similar age, sex and species. Representative lung retention curves presented on one baboon demonstrate the feasibility of lung clearance studies in these hand-reared animals. Due to its suitability for unsedated studies, this baboon model may be considered for other types of laboratory investigations.

The Marital Communication Inventory (MCI) is an extremely popular self-report measure of marital communication that has been used in over 65 dissertations and empirical articles since 1970, including several recent clinical reports that used the MCI as a principal outcome measure. However, contrary to its treatment in the clinical literature as a unidimensional, valid measure of treatment outcome, the MCI appears to be a multidimensional instrument, whose primary dimension may not be a specific style or method of communication. Using a canonical correlation analysis of data from over 200 midwestern wives, we compared MCI subscales with subscales from an abbreviated version of the Barrett-Lennard Relationship Inventory (RI). Results supported the hypothesis that the primary dimension of the MCI is more closely associated with positive regard than with the more specific communication dimensions of either empathy or congruence as measured by the RI. Future clinical research in the improvement of marital communication should use the MCI in a much more careful way in order to provide the most valid outcome data.

Loins from 1 2 - blood or 3 4 - to 7 8 - blood Charolais bulls (n = 60) and steers (n = 64) were obtained at 24 h post mortem from electrically stimulated sides and, at 12 days post mortem, steaks were removed and frozen. Shear force values were higher (P < 0·001) and sensory panel evaluations of tenderness and overall palatability were lower (P < 0·001) for steaks from bulls than from steers. No differences (P > 0·05) in connective tissue amount or off-flavour were detected for steaks from bulls versus steers. Significant correlations between carcass secondary sex characteristics and sensory panel evaluations of tenderness were noted, but the coefficients were not of a magnitude to be considered predictive of tenderness., (Copyright © 1985. Published by Elsevier Ltd.)

Seventy-two sides (eighteen sides from each sex-breed group) from carcasses of half-blood or three-quarters-to-seven-eighths-blood Charolais bulls or steers of known history and age, handled alike from weaning to slaughter, were used. All cattle were fed in a commercial feedlot (average days-on-feed was 186) and slaughtered in a commercial packing plant. Comparisons were made for percentages of (1) untrimmed wholesale cuts, (2) partially boneless subprimals (trimmed of fat in excess of 1·9 cm), (3) partially boneless retail-ready cuts (trimmed of fat in excess of 0·95 cm) and (4) boneless retail-ready cuts (trimmed of fat in excess of 0·95 cm). Bulls had higher percentages than steers of chuck and round at all stages of trim. Steers had higher percentages of untrimmed, wholesale loin and partially boneless shortloin (1·9 cm fat) than bulls but steer percentages of shortloin cuts trimmed to 0·95 cm of fat did not differ from those of bulls. Bulls averaged 48·05%, while steers averaged 45·45%, major boneless, closely trimmed retail-ready cuts. After the lean trim was adjusted to 25% chemical fat, bulls had 27·70% lean trim and 5·65% fat trim while steers had 24·30% lean trim and 12·15% fat trim. No difference in the percentage of retail-ready cuts was attributable to breed; however, the three-quarters-to-seven-eighths-blood Charolais group had a lower percentage of standardized fat trim and a slightly higher percentage of bone than the half-blood group., (Copyright © 1985. Published by Elsevier Ltd.)