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Understanding the genetic basis of complex phenotypes is a critical problem in medical and evolutionary genetics. The evolutionary forces of natural selection and demography have shaped patterns of worldwide genetic variation, which in turn have shaped the genetic architecture of human phenotypic variation. Admixed populations, including African Americans and Latinos, have recent ancestry from two or more ancestral groups and are highly underrepresented populations in human genetics research. As a result, the genetic variation that contributes to the genetic architecture of complex traits in these populations has largely been undefined. Here through a combination of data analysis, population genetic modeling and statistical genetics, we further our understanding of admixed populations and highlight the importance of studying diverse populations. First, in a study of bronchodilator drug response (BDR), we identified both population specific and shared genetic variants associated with differences in BDR in African American and Latino children with asthma. Second, in a study of Hispanics/Latinos, we show that admixture has been a dynamic process in the recent history of Mexican Americans, with ancestry proportions changing over time due to a complex mixture of small effects from several population and cultural factors. Finally, we draw attention to the biases and potential for continued health disparities that persist when utilizing genomic prediction based only on large samples of European individuals in Mexican Americans. Through these studies, we improved upon our understanding of the genetic diversity within admixed populations, its effects on human phenotypic diversity, and subsequently our ability to understand genetic contributions to complex traits and disease.

Let $G$ be a finite permutation group on $\Omega$. An ordered sequence $(\omega_1,\ldots,\omega_\ell)$ of elements of $\Omega$ is an irredundant base for $G$ if the pointwise stabilizer is trivial and no point is fixed by the stabilizer of its predecessors. If all irredundant bases of $G$ have the same cardinality, $G$ is said to be an IBIS group. Lucchini, Morigi and Moscatiello have proved a theorem reducing the problem of classifying finite primitive IBIS groups $G$ to the case that the socle of $G$ is either abelian or non-abelian simple. In this paper, we classify the finite primitive IBIS groups having socle an alternating group. Moreover, we propose a conjecture aiming to give a classification of all almost simple primitive IBIS groups., Comment: 6 pages

Family members of critically ill patients with COVID-19 have described increased symptoms of Post-Traumatic Stress Disorder (PTSD). Little is known about how these symptoms may change over time.We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12-months.This prospective, multi-site observational cohort study recruited participants at 12 hospitals in 5 states. Calls were made to participants at 3-4 months, 6-months, and 12-months post-patient admission to the ICU.There were 955 eligible family members, of whom 330 (53.3% of those reached) consented to participate. Complete longitudinal data was acquired for 115 individuals (34.8% of consented). PTSD symptoms were measured by the Impact of Events Scale-6 (IES-6), with a score of ≥10 identifying significant symptoms. At 3-months, the mean IES-6 score was 11.9±6.1 with 63.6% having significant symptoms, decreasing to 32.9% at one year (mean IES-6 score 7.6±5.0). Three clusters of symptom evolution emerged over time: persistent symptoms (34.8%, n=40), recovered symptoms (33.0%, n=38) and non-development of symptoms (32.2%, n=37). While participants identifying as Hispanic demonstrated initially higher adjusted IES-6 scores (2.57 points higher [95% CI: 1.1, 4.1, p =0.001]), they also demonstrated a more dramatic improvement in adjusted scores over time (4.7 greater decrease at 12 months [95% CI: 3.2-6.3, p.001]).One year later, some family members of patients with COVID-19 continue to experience significant symptoms of PTSD. Further studies are needed to better understand how various differences contribute to increased risk for these symptoms.

Background Hearing loss is the third leading global cause of disability and is associated with poorer quality of life. Hearing aids are often recommended for hearing loss; however, hearing aid uptake and use rates are perpetually low. Motivational interviewing (MI) is a patient-centered counseling aimed at addressing the desire in the patient to change their behavior. The aim of this study is to investigate the impact of one-on-one MI sessions on hearing aid use among new adult users. Methods A multi-center, prospective, randomized patient-blind controlled trial with a pre- and post-tests design. New hearing aid users ≥ 18 years of age will be recruited from Vancouver, Canada. They will be randomly assigned to a treatment or control group. The treatment group will attend a one-on-one MI session hosted by a practicing MI therapist in addition to standard in-person audiological care. The control group will receive standard in-person audiological care. Data is collected at baseline and at 1, 3, 6, and 12 months’ follow-ups. The primary outcomes are data-logged hearing aid use hours and patient-reported outcomes as measured by the International Outcome Inventory for Hearing Aids questionnaire. Associations between intervention and hearing aid use hours and self-reported outcome measures will be assessed. Discussion This trial is designed to evaluate the efficacy of one-on-one MI in improving hearing aid use in new adult users in the short and long terms. Results will contribute to the evidence on whether MI counseling has an effect on hearing aid use and may guide future clinical practices. Trial registration ClinicalTrials.gov NCT04673565. Registered on 17 December 2020.

This report describes the development of two photocatalytic methods for the pyridination of electron rich arenes. First, an SNAr-type reaction between aryl halides and pyridine is developed and optimized. This transformation affords selective substitution of C(sp2)-halogen over C(sp2)-OR bonds to afford arylpyridinium products under anaerobic conditions. Under complementary aerobic conditions, analogous substrates are shown to undergo oxidative C(sp2)-H pyridination.

The prime graph, or Gruenberg–Kegel graph, of a finite group 𝐺 is the graph Γ ⁢ ( G ) \Gamma(G) whose vertices are the prime divisors of | G | \lvert G\rvert and whose edges are the pairs { p , q } \{p,q\} for which 𝐺 contains an element of order p ⁢ q pq . A finite group 𝐺 is recognisable by its prime graph if every finite group 𝐻 with Γ ⁢ ( H ) = Γ ⁢ ( G ) \Gamma(H)=\Gamma(G) is isomorphic to 𝐺. By a result of Cameron and Maslova, every such group must be almost simple, so one natural case to investigate is that in which 𝐺 is one of the 26 sporadic simple groups. Existing work of various authors answers the question of recognisability by prime graph for all but three of these groups, namely the Monster, M \mathrm{M} , the Baby Monster, B \mathrm{B} , and the first Conway group, Co 1 \mathrm{Co}_{1} . We prove that these three groups are recognisable by their prime graphs.

ObjectiveAntineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol.MethodsAll patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction.ResultsA total of 186 eligible patients were included. Median age was 59.5 years (range 26–87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325–360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease.ConclusionsOur outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.

Subcrestal placement of implants may have interproximal bone proximity issues that interfere with the submucosal contour of implant-supported zirconia restorations during delivery of the restorations. Modification of the mesial distal submucosal areas may be necessary to fully seat the restoration without impingement of the interproximal bone. Our aim was to determine if modification of submucosal cervical contour of implant supported zirconia-titanium base (Zi-Ti base) restorations resulted in a significant change in fracture strength compared with Zi-Ti base restorations without any modification near the cervical submucosal area. Implant Zi-Ti base restorations designed in the form of a maxillary premolar were made for the Straumann implant lab analog. Zirconia samples were cemented onto the Ti-base and the test group (N = 20) underwent recontouring and polishing at the junction of the Zi-Ti base cervical areas. The control group (N = 20) did not undergo any modifications. All 40 samples underwent fracture testing with an Instron machine. We assessed differences between modified and unmodified implants restorations using a 2-tailed t test for independent samples. Fracture strength values (N) ranged from 4354.68 to 6412.49 in the test group (N = 20) and from 5400.31 to 6953.22 in the control group (N = 20). The average fracture strength in the control group (6154.84 ± 320.50) was higher than in the modified group (5593.13 ± 486.51; P < .001). Modification of submucosal contour significantly decreased fracture strength. However, the average fracture strength exceeded the masticatory forces of humans.

IMPORTANCE: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. OBJECTIVE: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. EXPOSURE: Having a family member in the ICU with COVID-19. MAIN OUTCOMES AND MEASURES: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). RESULTS: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients’ child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P

A 15-year-old female with no significant past medical history who presented with abdominal pain, vomiting, and diarrhea, found to be in acute renal failure and was subsequently diagnosed with multisystem inflammatory syndrome in children (MIS-C). Critical manifestations seen in pediatric COVID-19 can be varied affecting different organ systems. Pediatric providers, during a pandemic with imperfect testing, must be keenly aware of how varied the pathogenesis of COVID-19 can be in children.

Background Achieving maternal health outcomes in the SDGs requires the implementation of more targeted policies and strategies. While the MDGs may have deepened our understanding in this regard, we know little about the trends in maternal health services utilisation among primigravidas, and how age and geographical regions could have influenced these trends. In this study, we examined utilisation of antenatal and skilled delivery services among primigravidas in Uganda, a country with one of the highest maternal mortality ratios, and where early childbearing and its attendant challenges are common. Methods Guided by Andersen’s Behavioural Model, we fitted multivariate regression models to a pooled dataset of the 2006, 2011 and 2016 Ugandan Demographic and Health Survey (n = 3477) to understand the dynamics in Antenatal Care (ANC) and Skilled Birth Attendance (SBAs) utilisation among primigravidas. Post-estimation margins were employed to further highlight the effect of age and geographical regions. Results The analyses show an improvement in access to maternal health services among primigravidas from 2006 to 2016. Compared to 2006, primigravidas in 2016 were 48%, 24% and 2.98 times more likely to have early ANC, four or more ANC visits, and SBAs, respectively. Altogether, a primigravida in 2016 relative to 2006 was 42% more likely to meet all three maternal health service indicators. Post-estimation margins analyses on age and geographical disparities revealed that younger primigravidas have lower probability, while primigravidas in Eastern Region, one of the most deprived in the country, have the lowest probability of accessing maternal health services. Also, the study found education, wealth, women’s household decision-making power, place of residence as important determinants of ANC visits and SBAs. Conclusions Based on our findings, it is important to address the vulnerabilities of primigravidas, particularly younger individuals, in accessing early ANC. Uganda should scale-up decentralisation and integration of maternal health delivery in local communities as a strategy of addressing lingering geographical disparities, and ultimately improve maternal health outcomes in the SDGs period.

Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker associated with anatomical CAD burden and cardiovascular outcomes including myocardial infarction (MI) and death. We aimed to validate previous findings of the prognostic value of suPAR and to evaluate its diagnostic potential for functional relevant CAD (fCAD). Consecutive patients with suspected fCAD were enrolled. Adjudication of fCAD was performed blinded to suPAR concentrations by myocardial perfusion single-photon emission tomography (MPI-SPECT) and coronary angiography. Prognostic outcome measures included all-cause death, cardiovascular death, and incident MI during 2-year follow-up. Among consecutive 968 patients, suPAR concentrations were higher in patients with fCAD compared to those without (3.45 vs. 3.20 ng/mL, p = 0.007), but did not provide acceptable diagnostic accuracy (area under the curve [AUC]: 0.56, 95%CI 0.52–0.60). SuPAR correlated with high-sensitivity cardiac-troponin T (Spearman’s rho (ρ) 0.393, p ρ = 0.327, p ρ = 0.364, p ρ = 0.123, p p = 0.001). SuPAR was an independent predictor of all-cause death, without diagnostic utility for fCAD. NCT01838148

Academic self-efficacy is an essential element for effective and engaging learning. In order to improve academic self-efficacy, students need to engage in regular and effective self-reflection to form realistic beliefs about their own academic capabilities. However, students may not be motivated to sustain effective self-reflection. Suitable tools are needed to assist students to self-reflect effectively. The objectives of this study were to determine the effect of writing personalized weekly e-learning journals on students��� academic self-efficacy, the perception of its usefulness, and how it has helped students improve their academic self-efficacy. Multiple data collection methods were used in order to provide data for better explanations on the causality of the dependent and independent variables. Fifty-four students studying a degree program wrote personalized weekly e-learning journals over a ten-week period. Pre-tests and post-tests on their academic self-efficacy were administered in study week one and eleven respectively. The personalized weekly e-learning journals contained personalized prompts. The purposes of these prompts were not only to scaffold students to self-evaluate and self-reflective effectively but also to collect weekly time series data on academic self-efficacy and perceived usefulness in writing these journals. The post-test scores and time series data showed that the academic self-efficacy and the perceived usefulness of writing e-learning journals over the intervention period have improved. Writing personalized weekly e-learning journals has motivated the students to self-evaluate regularly, sustain their self-reflection, and promote positive academic self-efficacy. This study highlighted the benefits of writing personalized e-learning journals. Key words: academic self-efficacy, learning journals, self-reflection, higher education, time series L'auto-efficacit�� acad��mique est un ��l��ment essentiel pour un apprentissage efficace et engageant. Afin d'am��liorer leur auto-efficacit�� acad��mique, les ��tudiants doivent s'engager dans une autor��flexion r��guli��re et efficace pour se forger des convictions r��alistes sur leurs propres capacit��s acad��miques. Cependant, les ��tudiants peuvent ne pas toujours ��tre motiv��s pour mener une r��flexion personnelle efficace. Des outils ad��quats sont n��cessaires pour aider les ��tudiants �� s���engager dans une autor��flexion efficace. Les objectifs de cette ��tude ��taient de d��terminer l'effet de la r��daction de journaux hebdomadaires personnalis��s d'apprentissage en ligne sur l'auto-efficacit�� acad��mique des ��tudiants, la perception de l���utilit�� de cet exercice et la mani��re dont elle a aid�� les ��tudiants �� am��liorer leur auto-efficacit�� acad��mique. Plusieurs m��thodes de collecte de donn��es ont ��t�� utilis��es afin de fournir des donn��es permettant de mieux expliquer la causalit�� des variables d��pendantes et ind��pendantes. Cinquante-quatre ��tudiants suivant un programme menant �� un dipl��me ont r��dig�� des journaux hebdomadaires d'apprentissage en ligne personnalis��s sur une p��riode de dix semaines. Des pr��-tests et des post-tests sur leur auto-efficacit�� acad��mique ont ��t�� administr��s respectivement lors de la premi��re et de la onzi��me semaine d'��tude. Les journaux hebdomadaires d'apprentissage en ligne personnalis��s contenaient des messages-guides personnalis��s. Ces messages avaient pour but non seulement d'aider les ��tudiants �� s'auto-��valuer et �� r��fl��chir efficacement, mais aussi de recueillir des donn��es hebdomadaires sur l'auto-efficacit�� scolaire et l'utilit�� per��ue de la r��daction de ces journaux. Les r��sultats du post-test et les donn��es chronologiques ont montr�� que l'auto-efficacit�� acad��mique et l'utilit�� per��ue de la r��daction de journaux d'apprentissage en ligne se sont am��lior��es pendant la p��riode d'intervention. La r��daction de journaux hebdomadaires d'apprentissage en ligne personnalis��s a motiv�� les ��tudiants �� s'auto-��valuer r��guli��rement, �� soutenir leur autor��flexion et �� promouvoir une auto-efficacit�� acad��mique positive. Cette ��tude a mis en ��vidence les avantages de la r��daction de journaux d'apprentissage en ligne personnalis��s. Mots cl��s : auto-efficacit�� acad��mique; journaux d'apprentissage; autor��flexion; enseignement sup��rieur; s��rie chronologique, Alberta Journal of Educational Research, Vol. 67 No. 4 (2021): Winter

Purpose The impact of different screen-based typography styles on individuals’ cognitive processing of information has not been given much consideration in the literature, though such differences would imply different learning outcomes. This study aims to enrich the current understanding of the impact of reading in single- and multiple-column types on students’ cognitive processing. Design/methodology/approach An electroencephalogram (EEG) was used to record and analyze the brain signals of 27 students while reading from single- and multiple- column layouts. Findings The results showed a significant difference in students’ cognitive load when reading text from different types of columns. All students exerted less processing efforts when text was presented in two-column format, thus experiencing less cognitive load. Originality/value Using EEG, this study examined the neural consequences of reading in single- and multiple-column types on cognitive load during reading. The findings can be used to enrich the current instructional design practices on how different typographical formats facilitate learners’ cognitive performance.

Purpose This paper aims to investigate the influence of map design characteristics on users’ cognitive load and search performance. Two design conditions (symbolic vs non-symbolic) were used to evaluate users’ ability to locate a place of interest. Design/methodology/approach A total of 19 students (10 male and 9 female, 20-23 years old) participated in this study. The time required for subjects to find a place in the two conditions was used to estimate their searching performance. An electroencephalogram (EEG) device was used to examine students’ cognitive load using event-related desynchronization percentages of alpha, beta and theta brain wave rhythms. Findings The results showed that subjects needed more time to find a place in the non-symbolic condition than the symbolic condition. The EEG data, however, revealed that users experienced higher cognitive load when searching for a place in the symbolic condition. The authors found that the design characteristics of the map significantly influenced users’ brain activity, thus impacting their search performance. Originality/value Outcomes from this study can be used by cartographic designers and scholars to understand how certain design characteristics can trigger cognitive activity to improve users' searching experience and efficiency.

The potential safety hazards associated with the Mizoroki–Heck cross-coupling of bromobenzenes with styrenes were evaluated. The heat output from the reaction in various solvents was comparable in a variety of solvents; however, the rate of reaction was significantly faster in the presence of water. Thermal stability evaluation of the postreaction mixtures in DMSO and 3:1 DMSO/water by differential scanning calorimetry indicated that the onset temperatures of thermal decomposition were significantly lower than that of neat DMSO. Evaluation of the substrate scope revealed that the substitution pattern on the bromobenzene did not affect the heat output. The reaction rate of electron-deficient bromobenzenes was slower than that of the electron-rich bromobenzenes. In general, substituted styrenes afforded similar magnitudes of exotherms; however, the reaction rate of bromobenzene with 2-methylstyrene was significantly slower than the other studied styrenes. The predicted heat of reaction using the density fun...

In this Letter, we adapt a recently reported Pd-catalyzed transannular C(sp3)–H arylation of alicyclic amines for applications in fragment-based drug discovery (FBDD). We apply this method to the synthesis of a series of 6-arylated 3-azabicyclo[3.1.0]hexanes that are rule-of-three compliant fragments. Several modifications were made to the Pd-catalyzed C–H arylation method to enhance its utility in fragment synthesis. These include the use of microwave heating to shorten reaction times to under 1 h and the development of new approaches for directing group cleavage. Finally, we demonstrate that this fragment library falls within desirable physicochemical space for FBDD applications.

Objective: The Systematic Classic/Zhen Jiu Jia Yi Jing (ZJJYJ, 鍼灸甲乙經) is considered to be the first complete acupuncture manual to detail the location and meridian assignations of 349 acupuncture points. Despite numerous transcriptions and editing changes, many traditional acupuncturists adhere to the classics and rarely question their validity. However, ushering the use of acupuncture into the modern era requires examining acupuncture point locations objectively by comparing contemporary anatomical knowledge with classical texts. The aim of this research was to examine distinct neuroanatomical targets associated with acupuncture points to: (1) standardize the precise neuroanatomical target of each acupuncture point; and (2) crossreference neuroanatomical targets with classical point locations. This was done to demonstrate ancient authors' intentions when describing acupuncture points as coordinates used to stimulate the peripheral nervous system. Materials and Methods: The unique neuroanatomical targets associated with acupuncture points on the Foot Shao Yin Kidney meridian were defined. Specifically, KI 1 through KI 8 were examined by comparing classical point locations from the ZJJYJ with modern standardized textbook locations from Chinese Acupuncture and Moxibustion, current anatomical literature, the current authors' cadaver dissection research, and electrostimulation of acupuncture points in healthy volunteers. Results: KI 1–KI 8 correlated with motor entry points as well as with nerve branches and vessels derived from the posterior tibial neurovascular bundle. Conclusions: This research demonstrated a procedure to verify and standardize the distinct neuroanatomical structures of acupuncture points. Standardization of neuroanatomical targets of acupuncture points will enable researchers and clinicians to obtain reproducible results in clinical treatments and research protocols.

Background Sarcopenia is associated with postoperative complications in inflammatory bowel disease. It has most commonly been defined using the skeletal muscle index, computed after analysis of cross-sectional muscle area at L3. Psoas muscle thickness normalized to height (PMTH), which is easier to derive, is a potential surrogate of SMI and sarcopenia in patients with cirrhosis and chronic pancreatitis. We investigate whether sarcopenia defined by PMTH has utility in predicting post-operative outcomes in patients with inflammatory bowel disease. Methods We performed a retrospective study of adults undergoing IBD-related surgery from 2009 to 2019 at two hospitals. Sarcopenia was defined by sex-specific PMTH at the umbilicus on cross-sectional imaging using a 50th percentile median cutoff. Predictive models were created using variables (BMI, age, sex, smoking status, albumin, INR, platelets, hemoglobin, hypertension, diabetes, CAD, medications) that may be associated with complications (mortality, reoperation, readmission, transfusions, ICU admission, infection, DVT/PE), and sarcopenia for comparison. Results 85 patients with IBD were included. Lower albumin level (OR = 0.52, p = 0.039) and biologic use (OR = 5.92, p = 0.006) were associated with postoperative complications. There was no significant difference using PMTH compared to a model incorporating hypoalbuminemia and biologic use in predicting complications. Sarcopenia on univariate analysis was associated with a lower 30 day rate of reoperation (p = 0.04). Conclusions A low status of PMTH was not associated with increased postoperative complications, however hypoalbuminemia and biologic use were. PMTH as a surrogate for sarcopenia requires further study, ideally with prospective studies comparing PMTH with accepted radiographic surrogates for sarcopenia, to determine its role in clinical decision making.