tbuckley/cabot-search huggingface dataset:
Soundings: Arise, Sir Lancelot
Authors: James Owen Drife
Journal: BMJ (1999)

Greying beard, dark suit, middle age spread, consultant status. Coincidence, or have I been subconsciously working on my image? Anyone over 50 feels like a youngster in an ageing body, but for a few of us, Simon Sparrow is trapped inside Lancelot Spratt.

Doctor in the House was published in 1952, when I was 4 years old. The film was produced in 1954 by Betty Box, who died recently. Sir Lancelot was played by James Robertson Justice, who died 24 years ago. The images, however, live on, giving the book’s last words a prophetic quality: “From now on it was always going to be like this.”

With screen doctors spanning the alphabet from Cameron through Gillespie to Zhivago, why should Spratt remain the most recognisable? One reason is the brilliant portrayal. James Robertson Justice (a name impossible to shorten) was a former naturalist and journalist and his intelligence showed. Today’s directors prefer senior consultants to be played by cardboard actors with untwinkling eyes.

The main reason, though, is that Sir Lancelot is like Santa Claus. Deep down, everyone wants to believe that he exists. Richard Gordon’s creation was humane beneath his bluster, but what still attracts us is his armour plated self assurance. He is the embodiment of what zoologists call the dominant male. As Desmond Morris keeps reminding us, humans are little different from our cousins the apes. Like them, we are programmed to be part of a hierarchy. The leader may be challenged but nobody likes to see him bleed.

Nowadays, however, an unreconstructed Sir Lancelot would last about 48 hours before a whistleblower reported his bad attitude. This sets a problem for his successors. Can we reconcile the primordial need for leadership with the current distaste for medical authoritarianism?

The quandary was brought home to me recently during a meeting which included some routine doctor bashing from consumer representatives. The medical profession, they said, is still as arrogant as it was in 1952. Silence would have meant assent but taking offence reinforced the irascible stereotype.

We usually cope by agreeing, finding scapegoats, and looking for leadership from outside medicine. Better, I think, to rediscover our self confidence. We can banish paternalism from the individual consultation without completely abrogating our collective authority.
Variation of Thyroidectomy-Specific Outcomes Among Hospitals and Their Association With Risk Adjustment and Hospital Performance
Authors: Jason B. Liu, Julie A. Sosa, Raymon H. Grogan, Yaoming Liu, Mark E. Cohen, Clifford Y. Ko, Bruce L. Hall
Journal: JAMA Surgery (2017)

Current surgical quality metrics might be insufficient to fully judge the quality of certain operations because they are not procedure specific. Hypocalcemia, recurrent laryngeal nerve (RLN) injury, and hematoma are considered to be the most relevant outcomes to measure after thyroidectomy. Whether these outcomes can be used as hospital quality metrics is unknown.To evaluate whether thyroidectomy-specific outcomes vary among hospitals, whether the addition of thyroidectomy-specific variables affects risk adjustment, and whether differences in hospital performance are associated with thyroidectomy-specific care processes.In this retrospective cohort study, patients undergoing thyroidectomies from January 1, 2013, through December 31, 2015, at hospitals participating in the American College of Surgeons' National Surgical Quality Improvement Program were studied.Thyroidectomy-related care.Clinically severe hypocalcemia, RLN injury, and clinically significant hematoma within 30 days of thyroid surgery and hospital-level performance variation, change in risk adjustment, and association with processes.Overall, 14 540 patients (mean [SD] age, 52.1 [15.0] years; 11 499 [79.1%] female) underwent operations at 98 hospitals. Because operations missing thyroidectomy-specific outcomes were excluded, the numbers of operations and hospitals analyzed differed by outcome. Of 14 540 operations included, clinically severe hypocalcemia occurred in 450 patients (3.3% overall, 0.6% after partial, and 4.7% after subtotal or total thyroidectomy), RLN injury in 755 patients (5.7% overall, 4.2% after partial, and 6.6% after subtotal or total thyroidectomy), and hematoma in 175 patients (1.3%). Hospital performance varied for hypocalcemia and RLN injury but not for hematoma. Hospital performance rankings were largely unaffected by the inclusion of thyroidectomy-specific data in risk adjustment. With regard to processes, patients undergoing thyroidectomies at the best-performing vs worst-performing hospitals less frequently had their postoperative parathyroid hormone level measured (593 [19.9%] vs 457 [31.7%], P < .001) and more often were prescribed oral calcium, vitamin D, or both (2281 [76.6%] vs 962 [66.8%], P < .001). When profiled by RLN injury, use of energy devices (1517 [69.1%] vs 507 [55.2%], P < .001) and intraoperative nerve monitoring (1223 [55.7%] vs 346 [37.7%], P < .001) were more prevalent at the best- compared with the worst-performing hospitals.Postoperative hypocalcemia and RLN injury, but not hematoma, potentially could be used as thyroidectomy-specific national hospital quality improvement metrics. Strategies aimed at reducing these complications after thyroidectomy may improve the care of these patients.
Identifying prognostic factors for conservative treatment outcomes in servicemen with chronic exertional compartment syndrome treated at a rehabilitation center
Authors: Mariëtte Z. Meulekamp, Peter van der Wurff, Alfred van der Meer, Cees Lucas
Journal: Military Medical Research (2017)

Chronic exertional compartment syndrome (CECS) is a condition of pain induced by exercise, and it is characterized by muscle swelling and impaired muscle function in the lower leg. Given the diversity in the diagnosis and treatment of CECS, it is desirable to determine variables pertaining to prognosis and recovery. The purpose of this study is to identify prognostic factors for conservative treatment outcomes in servicemen with CECS who were treated at a Military Rehabilitation Center. Patients from all military services were referred from the special unit for lower leg pain at the Central Military Hospital, Utrecht, the Netherlands. Descriptive analysis was used to report the characteristics of the participants and their baseline measurements. Group differences were analyzed using a Student's t-test or Mann-Whitney U test, according to the normality of the data distribution. Differences between the pre- and post-intervention outcomes were evaluated using the Wilcoxon signed rank test. To evaluate the magnitude of prognostic factors, a univariate logistic regression analysis was performed. The prognostic factors included age, body mass index, body fat percentage, self-efficacy beliefs, foot malalignment, intramuscular pressure, other comorbidities, protein and creatine use, smoking, alcohol use, complaint duration, physical demands, and duration of military service. After the rehabilitation period, we observed 25 patients with a successful outcome, which was defined as a reduction in pain (≥ 2 points) during the capacity test measured using a verbal rating scale and 20 patients with an unsuccessful outcome. Factors demonstrating a limited increased odds ratio for an unsuccessful outcome included smoking, alcohol use, intramuscular pressure, a complaint duration of more than 6 months, and physical demands of service. However, these factors did not reach significance. This study did not identify any prognostic factors that predict the outcome of a rehabilitation program for CECS. A larger sample using an identical design might provide further evidence regarding prognostic factors, which would facilitate development of a model that predicts the outcomes of a rehabilitation program for CECS.
Abstract 16695: Intraoperative Circulating-Brain Biomarker is Associated With Neurodevelopmental Outcomes at 1 Year in Neonates Undergoing Cardiac Surgery
Authors: Eric M Graham, Renee' H Martin, Andrew M Atz, Kasey Hamlin-Smith, Bahaaldin Alsoufi, William T Mahle, Allen D Everett
Journal: Circulation (2017)

Background:  Neurodevelopmental disability is the most significant complication for survivors of surgery for congenital heart disease. The ability to detect brain injury in real time remains elusive. This study sought to determine if perioperative circulating-brain injury biomarker levels are associated with neurodevelopmental outcomes at 12 months of age.   Methods:  A secondary analysis of a multicenter randomized controlled trial of neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB) was performed. The brain injury biomarker glial fibrillary acidic protein (GFAP) was measured in blood at 4 time points: 1) prior to skin incision, 2) immediately after CPB, 3) 4 and 4) 24 hours post-operatively. Univariate and multivariable analysis was used to determine an association with peak levels of GFAP and Bayley Scale of Infant Development III (BSID) composite scores.   Results:  There were 97 subjects who had cardiac surgery at a mean age of 9 ± 6 days and completed a BSID at 12.5 ± 0.6 months of age. BSID mean scores were cognitive 105 ± 15, language 101 ± 13, and motor 92 ±17. GFAP levels are shown in Fig 1A. In univariate analysis peak GFAP was inversely associated with cognitive (p=0.02), language (p=0.03) and motor (p   Conclusions:  Higher GFAP levels were independently associated with decreased BSID motor composite scores at 12 months. GFAP may serve as a diagnostic means to acutely identify perioperative brain-specific injury and serve as a benchmark of therapeutic efficacy for investigational treatments, discriminate center specific effects and early prognostic information for intervention.
P2.03a-009 Clinical Outcome of Node-Negative Oligometastatic Non-Small Cell Lung Cancer
Authors: Masayuki Takeda, Kiyohiro Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Takeshi Okuda, Amami Kato, Yasumasa Nishimura, Tetsuya Mitsudomi, Atsuko Koyama, Kazuhiko Nakagawa
Journal: Journal of Thoracic Oncology (2017)
A Combination of Allogeneic Stem Cells Promotes Cardiac Regeneration
Authors: Makoto Natsumeda, Victoria Florea, Angela C. Rieger, Bryon A. Tompkins, Monisha N. Banerjee, Samuel Golpanian, Julia Fritsch, Ana Marie Landin, Nilesh D. Kashikar, Vasileios Karantalis, Viky Y. Loescher, Kostas E. Hatzistergos, Luiza Bagno, Cristina Sanina, Muzammil Mushtaq, Jose Rodriguez, Marcos Rosado, Ariel Wolf, Kevin Collon, Louis Vincent, Anthony J. Kanelidis, Ivonne H. Schulman, Raul Mitrani, Alan W. Heldman, Wayne Balkan, Joshua M. Hare
Journal: Journal of the American College of Cardiology (2017)
Abstract 14889: Ckit Expression in Vascular Smooth Muscle Cells Protects Mice Against Excessive Atherosclerosis
Authors: Lei Song, Guillermo Selman, Nieve Santos, Laisel Martinez, Roberta M Lassance-Soares, Keith Webster, Roberto Vazquez Padron
Journal: Circulation (2016)

Introduction:  We have previously demonstrated that global deficiency of cKit, an important receptor tyrosine kinase, exacerbates atherosclerosis in hyperlipidemic mice. This study aims at demonstrating the protective role of c-Kit in smooth muscle cells (SMCs) against atherogenesis, and the mechanism underlying.   Methods and Results:  Atherosclerosis was assessed in triple transgenic mice with cKit targeted deletion in SMCs. In this model, atherosclerotic burden was significantly increased in c-Kit deficient mice versus control littermates. The loss of cKit was associated with medial SMCs hypertrophy, hypercellularity, and reduced expression of “contractile” proteins in aortas. In vitro, cKit-deficient aortic SMCs proliferated faster and migrated more than those from wild type controls. The absence of cKit made SMCs prone to acquire a foam-like phenotype secondary to increased activity of the Kruppel like factor 4 (KLF4), a transcriptional factor that favors SMC pathological synthetic phenotype. Rescue of cKit in deficient SMCs led to decreased level of KLF4, restored contractile markers, and prevented foam cell formation.   Conclusion:  This study provides mechanistic evidence that vascular cKit is involved in controlling SMCs phenotype and is atheroprotective in hyperlipidemic mice.
Junior doctors are being left to run hospital departments unsupervised, GMC warns
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Junior doctors in some UK hospitals are being forced to work beyond their capabilities and to run busy departments unsupervised, putting patients at risk, the General Medical Council has warned.

In its UK-wide report on training environments in 2017 the GMC describes examples of trainees being left to deal with “situations beyond their competence” because of an absence of senior supervising doctors.1 This was being driven by recruitment difficulties, the regulator said.

The report was based on the GMC’s annual survey, which is answered by 53 000 junior doctors and 24 000 trainers.

More than a sixth (8256) junior doctors surveyed said that they felt forced to …
Abstract 15223: Impact of Contact Force Sensing on Outcomes During Ablation of Persistent Atrial Fibrillation: The Multicenter, Randomized TOUCH AF Trial
Authors: Hong Euy Lim, Sergio Conti, Jean Champagne, Laurent Macle, Paul Novak, Rukshen Weerasooriya, Atul Verma
Journal: Circulation (2016)

Introduction: The impact of contact force sensing (CFS) on outcomes of ablation of persistent atrial fibrillation (AF) is unknown. Hypothesis: The TOUCH AF trial (NCT01851525) compared a CFS-guided...
A phase II study of milciclib (PHA-848125AC) in patients (pts) with thymic carcinoma (TC).
Authors: Benjamin Besse, Marina Chiara Garassino, Arun Rajan, Silvia Novello, Julien Mazieres, Glen J. Weiss, Marina Ciomei, Marcella Martignoni, Anna Petroccione, Cristina Davite, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2014)

7526 Background: TC and B3 thymoma (B3T) are rare malignant tumors of the thymus. Outcomes of clinical trials focusing on TC and B3T have highlighted the challenging nature of this disease and the need to identify new agents. Milciclib is an inhibitor of cyclic-dependent kinase and Src family members, and a limited number of additional kinases. We have initiated a single-arm Phase II study in advanced TC/B3T based on 2 partial responses (PRs, one pt with thymic carcinoma and one pt with B3 thymoma) observed in a phase I study conducted with Milciclib. Methods: Pts with histologically confirmed TC/B3T who received only one prior systemic therapy were enrolled. Pts received Milciclib 150 mg daily 7d on/7d off in 2-week cycles. The primary endpoint was progression free survival rate at 3 months (PFS-3 rate). Based on the Simon's 2-stage design, the sample size of 54 evaluable pts confers 80% power to reject the null hypothesis of a PFS-3 rate lower than 33% . At least 14 successes out of 54 evaluable patients were required for Milciclib to deserve further investigation. Results: To date, 43 pts have been treated (male/female 18/25; median age 55, range 21-80, TC/B3T 26/9). The second stage of the trial is ongoing and 599 cycles have been administered with a median number of 7 cycles/pts. Out of 30 pts whose data are available and mature, 14 are successes (PFS-3 rate = 46.7%; 95%CI 28.3-65.7%) including a RECIST 1.1 PR. Toxicity was generally moderate. The most common Grade 3-4 AE are nausea and asthenia (8.3%), vomiting, myasthenic syndrome, dehydration, hypophosphatemia, cytolytic hepatitis, plantar fascitis (4.2%). The most common Grade 3-4 hematological and biochemical toxicities are neutropenia (8.4%), creatinine, amylase and lipase increase (5.6%). Conclusions: The study has already met its predefined primary endpoint in treated patients and therefore we thought it was useful to report these data in a rare disease although the per protocol analysis is to be done on evaluable patients. This supports its full investigation as potential new therapeutic agent to treat TC/B3T. Clinical trial information: NCT01011439.
Orange is the new aesthetic
Authors: Anjan Chatterjee
Journal: Behavioral and Brain Sciences (2017)

Abstract The Distancing-Embracing model proposes that negative emotions are constitutive of aesthetic experiences. This move is welcome and adds depth to empirical aesthetics. However, the model's emphasis on temporality challenges how best to think of static art forms. I suggest that “decisive” and “distilled” moments dilate time in the viewer's mind and might allow the model to accommodate photography and painting.
Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese
Authors: Jacob Gratten, Qiongyi Zhao, Beben Benyamin, Fleur Garton, Ji He, Paul J. Leo, Marie Mangelsdorf, Lisa Anderson, Zong-Hong Zhang, Lu Chen, Xiang-Ding Chen, Katie Cremin, Hong-Weng Deng, Janette Edson, Ying-Ying Han, Jessica Harris, Anjali K. Henders, Zi-Bing Jin, Zhongshan Li, Yong Lin, Xiaolu Liu, Mhairi Marshall, Bryan J. Mowry, Shu Ran, David C. Reutens, Sharon Song, Li-Jun Tan, Lu Tang, Robyn H. Wallace, Lawrie Wheeler, Jinyu Wu, Jian Yang, Huji Xu, Peter M. Visscher, Perry F. Bartlett, Matthew A. Brown, Naomi R. Wray, Dongsheng Fan
Journal: Genome Medicine (2017)

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry. The importance of trans-ethnic studies in human genetic studies is widely recognised, yet a dearth of studies of non-European ancestries remains. Here, we report analyses of novel whole-exome sequencing (WES) data from Chinese ALS and control individuals. WES data were generated for 610 ALS cases and 460 controls drawn from Chinese populations. We assessed evidence for an excess of rare damaging mutations at the gene level and the gene set level, considering only singleton variants filtered to have allele frequency less than 5 × 10–5 in reference databases. To meta-analyse our results with a published study of European ancestry, we used a Cochran–Mantel–Haenszel test to compare gene-level variant counts in cases vs controls. No gene passed the genome-wide significance threshold with ALS in Chinese samples alone. Combining rare variant counts in Chinese with those from the largest WES study of European ancestry resulted in three genes surpassing genome-wide significance: TBK1 (p = 8.3 × 10–12), SOD1 (p = 8.9 × 10–9) and NEK1 (p = 1.1 × 10–9). In the Chinese data alone, SOD1 and NEK1 were nominally significantly associated with ALS (p = 0.04 and p = 7 × 10–3, respectively) and the case/control frequencies of rare coding variants in these genes were similar in Chinese and Europeans (SOD1: 1.5%/0.2% vs 0.9%/0.1%, NEK1 1.8%/0.4% vs 1.9%/0.8%). This was also true for TBK1 (1.2%/0.2% vs 1.4%/0.4%), but the association with ALS in Chinese was not significant (p = 0.14). While SOD1 is already recognised as an ALS-associated gene in Chinese, we provide novel evidence for association of NEK1 with ALS in Chinese, reporting variants in these genes not previously found in Europeans.
The “appropriate” response to deprivation: Evolutionary and ethical dimensions
Authors: Christopher Lewis, David M G Lewis
Journal: Behavioral and Brain Sciences (2017)

Abstract Pepper &amp; Nettle use an evolutionary framework to argue that “temporal discounting” is an appropriate response to low socioeconomic status (SES), or deprivation. We suggest some conceptual refinements to their “appropriate-response” perspective, with the hope that it usefully informs future research on and public policy responses to the relationship between deprivation and temporal discounting.
Abstract 21391: Combined Aerobic and Inspiratory Muscle Training Versus Aerobic Training Alone in Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Authors: Yu-Shan Lin, Li-Ying Wang, Hsin-Yi Huang, Bo-Yan Chen, Wei-Ning Hsu
Journal: Circulation (2017)

Background: Abnormal ventilatory response contributes to exercise intolerance in patients with chronic heart failure (CHF). Previous meta-analysis showed that inspiratory muscle training (IMT) is beneficial for improving respiratory muscle strength and functional capacity in patients with CHF. However, whether the combination of IMT and aerobic training (AT) could further improve ventilatory response during exercise in patients with CHF is not clear. Purpose: The aim of this meta-analysis was to investigate the effect of IMT in combination with AT on ventilatory response during exercise in patients with CHF. Methods: We searched the following electronic databases (from inception to January 2017): PubMed, Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (from January 2000 to January 2017) for relevant literature. We included randomized controlled trials (RCT) that compared IMT+AT with AT in which the outcomes was to assess ventilatory response (peak oxygen uptake and minute ventilation/carbon dioxide production (VE/VCO2) slope), and maximal inspiratory pressure (PImax)) during exercise in patients with CHF. A random-effects model was used for the main analysis. Results: Of 63 identified studies, three RCTs with a total of 94 CHF patients met the inclusion criteria. Compared to AT alone, combined IMT and AT significantly increased PImax (mean difference 18.7 cmH2O, 95% CI: 10.2 to 27.2; p&lt;0.0001) but had no effect on peak oxygen uptake (mean difference 0.7; 95% CI: -1.3 to 2.7; p=0.49) or VE/VCO2 slope (mean difference -2.8; 95%CI: -8.1 to 2.6; p=0.31). Subgroup analyses showed intensive inspiratory training makes further improvement in PImax and Minnesota Living with Heart Failure Questionnaire (mean difference -4.22; 95% CI -7.69 to -0.75; p=0.02), irrespective of baseline inspiratory muscle strength and ejection fraction. Conclusions: The results showed that in patients with CHF, IMT in combination with AT training could improve respiratory muscle strength but had no impact on ventilatory response during exercise. These findings suggested that the inspiratory muscle insufficiency might not be the main cause for abnormal ventilatory response during exercise in patients with CHF.
Implantable Cardioverter-Defibrillators in Patients With a Continuous-Flow Left Ventricular Assist Device
Authors: Kevin J. Clerkin, Veli K. Topkara, Ryan T. Demmer, Jose M. Dizon, Melana Yuzefpolskaya, Justin A. Fried, Xingchen Mai, Donna M. Mancini, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Paolo C. Colombo, A. Reshad Garan
Journal: JACC Heart Failure (2017)