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Concept: Group theory

244

Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. Results At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group. Conclusions As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence-free survival than placebo, with no new toxic effects identified. (Funded by Merck; ClinicalTrials.gov number, NCT02362594 ; EudraCT number, 2014-004944-37 .).

Concepts: Clinical trial, Cancer, Cancer staging, Clinical research, Placebo, Group theory, Toxicity

182

The aim of this longitudinal study was to assess whether correction of unilateral posterior crossbite in the primary dentition results in improvement of facial symmetry and increase of palatal surface area and palatal volume. A group of 60 Caucasian children in the primary dentition, aged 5.3 ± 0.7 years, were collected at baseline. The group consisted of 30 children with a unilateral posterior crossbite with midline deviation of at least 2 mm (CB) and 30 without malocclusion (NCB). The CB group was treated using an acrylic plate expander. The children’s faces and dental casts were scanned using a three-dimensional laser scanning device. Non-parametric tests were used for data analysis to assess differences over the 30 months period of follow-up. The CB children had statistically significantly greater facial asymmetry in the lower part of the face (P < 0.05) and a significantly smaller palatal volume (P < 0.05) than the NCB children at baseline. There were no statistically significant differences between the two groups at 6, 12, 18, and 30 months follow-ups. Treatment of unilateral posterior crossbite in the primary dentition period resulted in an improvement of facial symmetry in the lower part of the face (P < 0.05) and increase of the palatal surface area and palatal volume (P < 0.001). At 30 months, relapse was observed in eight children (26.7 per cent). Treatment of unilateral posterior crossbite in the primary dentition improves facial symmetry and increases the palatal surface area and the palatal volume, though it creates normal conditions for normal occlusal development and skeletal growth.

Concepts: Statistical significance, Sociology, Group theory, Area, Asymmetry, Facial symmetry

172

BACKGROUND: The symptom of tongue deviation is observed in a stroke or transient ischemic attack. Nevertheless, there is much room for the interpretation of the tongue deviation test. The crucial factor is the lack of an effective quantification method of tongue deviation. If we can quantify the features of the tongue deviation and scientifically verify the relationship between the deviation angle and a stroke, the information provided by the tongue will be helpful in recognizing a warning of a stroke. METHODS: In this study, a quantification method of the tongue deviation angle was proposed for the first time to characterize stroke patients. We captured the tongue images of stroke patients (15 males and 10 females, ranging between 55 and 82 years of age); transient ischemic attack (TIA) patients (16 males and 9 females, ranging between 53 and 79 years of age); and normal subjects (14 males and 11 females, ranging between 52 and 80 years of age) to analyze whether the method is effective. In addition, we used the receiver operating characteristic curve (ROC) for the sensitivity analysis, and determined the threshold value of the tongue deviation angle for the warning sign of a stroke. RESULTS: The means and standard deviations of the tongue deviation angles of the stroke, TIA, and normal groups were: 6.9 [PLUS-MINUS SIGN] 3.1, 4.9 [PLUS-MINUS SIGN] 2.1 and 1.4 [PLUS-MINUS SIGN] 0.8 degrees, respectively. Analyzed by the unpaired Student’s t-test, the p-value between the stroke group and the TIA group was 0.015 (>0.01), indicating no significant difference in the tongue deviation angle. The p-values between the stroke group and the normal group, as well as between the TIA group and the normal group were both less than 0.01. These results show the significant differences in the tongue deviation angle between the patient groups (stroke and TIA patients) and the normal group. These results also imply that the tongue deviation angle can effectively identify the patient group (stroke and TIA patients) and the normal group. With respect to the visual examination, 40% and 32% of stroke patients, 24% and 16% of TIA patients, and 4% and 0% of normal subjects were found to have tongue deviations when physicians “A” and “B” examined them. The variation showed the essentiality of the quantification method in a clinical setting. In the receiver operating characteristic curve (ROC), the Area Under Curve (AUC, = 0.96) indicates good discrimination. The tongue deviation angle more than the optimum threshold value (= 3.2[DEGREE SIGN]) predicts a risk of stroke. CONCLUSIONS: In summary, we developed an effective quantification method to characterize the tongue deviation angle, and we confirmed the feasibility of recognizing the tongue deviation angle as an early warning sign of an impending stroke.

Concepts: Stroke, Transient ischemic attack, Statistical significance, Student's t-test, Group theory, Normal distribution, Standard deviation, Receiver operating characteristic

171

Cognitive theories on deception posit that lying requires more cognitive resources than telling the truth. In line with this idea, it has been demonstrated that deceptive responses are typically associated with increased response times and higher error rates compared to truthful responses. Although the cognitive cost of lying has been assumed to be resistant to practice, it has recently been shown that people who are trained to lie can reduce this cost. In the present study (n = 42), we further explored the effects of practice on one’s ability to lie by manipulating the proportions of lie and truth-trials in a Sheffield lie test across three phases: Baseline (50% lie, 50% truth), Training (frequent-lie group: 75% lie, 25% truth; control group: 50% lie, 50% truth; and frequent-truth group: 25% lie, 75% truth), and Test (50% lie, 50% truth). The results showed that lying became easier while participants were trained to lie more often and that lying became more difficult while participants were trained to tell the truth more often. Furthermore, these effects did carry over to the test phase, but only for the specific items that were used for the training manipulation. Hence, our study confirms that relatively little practice is enough to alter the cognitive cost of lying, although this effect does not persist over time for non-practiced items.

Concepts: Truth, Training, Practice, Group, Group theory, Concept, Lie, Deception

169

Finite simple groups are the building blocks of finite symmetry. The effort to classify them precipitated the discovery of new examples, including the monster, and six pariah groups which do not belong to any of the natural families, and are not involved in the monster. It also precipitated monstrous moonshine, which is an appearance of monster symmetry in number theory that catalysed developments in mathematics and physics. Forty years ago the pioneers of moonshine asked if there is anything similar for pariahs. Here we report on a solution to this problem that reveals the O'Nan pariah group as a source of hidden symmetry in quadratic forms and elliptic curves. Using this we prove congruences for class numbers, and Selmer groups and Tate-Shafarevich groups of elliptic curves. This demonstrates that pariah groups play a role in some of the deepest problems in mathematics, and represents an appearance of pariah groups in nature.Classifying groups is an important challenge in mathematics and has led to the identification of groups which do not belong to the main families. Here Duncan et al. introduce a type of moonshine which is a connection between these groups, number theory and potentially physics.

Concepts: Mathematics, Physics, Group, Group theory, Number, Modular arithmetic, Number theory, Monstrous moonshine

139

This study was aimed to introduce a novel entry point for pedicle screw fixation in the thoracic spine and compare it with the traditional entry point. A novel entry point was found with the aim of improving accuracy, safety and stability of pedicle screw technique based on anatomical structures of the spine. A total of 76 pieces of normal thoracic CT images at the transverse plane and the thoracic pedicle anatomy of 6 cadaveric specimens were recruited. Transverse pedicle angle (TPA), screw length, screw placement accuracy rate and axial pullout strength of the two different entry point groups were compared. There were significant differences in the TPA, screw length, and the screw placement accuracy rate between the two groups (P<0.05). The maximum axial pullout strength of the novel entry point group was slightly larger than that of the traditional group. However, the difference was not significant (P>0.05). The novel entry point significantly improved the accuracy, stability and safety of pedicle screw placement. With reference to the advantages above, the new entry point can be used for spinal internal fixations in the thoracic spine.

Concepts: Vertebral column, Symmetry, Group, Group theory, Anatomy, Human anatomy, Thoracic vertebrae, Space group

33

Setting personal targets is an important behavioural component in weight management programmes. Normal practice is to encourage ‘realistic’ weight loss, although the underlying evidence base for this is limited and controversial. The present study investigates the effect of number and size of weight-loss targets on long-term weight loss in a large community sample of adults.

Concepts: Present, Time, Weight loss, Force, Group theory, Meta-analysis, Evidence-based management

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BACKGROUND: Concerns have been voiced regarding the impact of the European Working Time Directive (EWTD) on surgical training. Following its introduction (August 2009) in Wexford General Hospital, Ireland Surgical Senior House Officers (SSHOs) are required to leave the hospital at 10 a.m. the morning after on-call duty. This study investigates the consequences of this practice on operative experience gained by six SSHOs in comparison to their predecessors. METHODS: A prospectively maintained database of surgical procedures was interrogated. Operative experience of SSHOs over a 5-month period (August-December 2009) was compared with that of colleagues 1 year earlier. The primary endpoint was overall operative volume of SSHOs. Subgroup analysis was performed of cases by primary operator versus assistant, intermediate versus minor procedures and by team. Comparison was made of operative volume between Group 1 (pre-EWTD) and Group 2 (post-EWTD). RESULTS: Operative volume for Group 1 (pre-EWTD) was 461 cases. Group 2 (post-EWTD) was involved in a total of 349 operations, showing a decrease of 24 % (P = 0.006). SSHOs in Group 1 (pre-EWTD) had been the primary operator in 109 cases compared to 87 in Group 2 (post-EWTD), demonstrating a reduction of 20 % (P = 0.06). Most worryingly, there was a reduction of 63 % (P = 0.04) in the intermediate cases performed as operating surgeon in Group 2 (post-EWTD). CONCLUSIONS: The present data set demonstrates a significant reduction in operative experience gained by SSHOs after local implementation of the EWTD. A major challenge facing Irish surgical training over the next decade is reduced operative exposure in the clinical setting.

Concepts: Hospital, Surgery, Group theory, Demonstration, The Europeans, Senior house officer

28

PURPOSE: To investigate the MRI characteristics in a large cohort of multiple sclerosis (MS) patients with and without a family history of MS. METHODS: Enrolled in this prospective study were 758 consecutive MS patients (mean age 46.2 ± 10.1 years, disease duration 13.6 ± 9.2 years and EDSS 3.4 ± 2.1), of whom 477 had relapsing-remitting, 222 secondary-progressive, and 30 primary-progressive disease courses and 29 had clinically isolated syndrome. One hundred and ninety-six patients (25.9%) had a positive family history of MS. Patients were assessed using measurements of lesions, brain atrophy, magnetization transfer ratio (MTR) and diffusion-weighted imaging. RESULTS: The familial MS group had greater T1-lesion volume (p=0.009) and a trend for lower MTR of T1-lesion volume (p=0.047) than the sporadic MS group. No clinical differences were found between familial versus sporadic group, or by a degree of affected relative subgroups. CONCLUSIONS: While familial MS was associated with more severe T1-lesion volume and its MTR characteristics, there were no clinical status differences between familial and sporadic MS patients. Therefore, a better understanding of the genetic and/or epigenetic influences causing these differences can advance the understanding and management of MS.

Concepts: Family, Epidemiology, Magnetic resonance imaging, Multiple sclerosis, Clinically isolated syndrome, Group, Group theory, Family history

26

Team-based learning (TBL), a structured form of small-group learning, has gained popularity in medical education in recent years. A growing number of medical schools have adopted TBL in a variety of combinations and permutations across a diversity of settings, learners, and content areas. The authors conducted this systematic review to establish the extent, design, and practice of TBL programs within medical schools to inform curriculum planners and education designers.

Concepts: Medicine, Education, Physician, Group theory, Medical school, Binomial coefficient, Combinatorics