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Background: Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT. Methods: We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study. Results: Twenty-one genetic loci were discovered at P −8 . Several novel candidate genes were identified including PROX1 , PXN , and PTK2 , with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13–1.23]) with pairwise analyses demonstrating a moderate genetic correlation (r g =0.53) and substantial loci overlap (19/21). Conclusions: Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.

BACKGROUND Over the last 50 years, the epidemiology of hypertrophic cardiomyopathy (HCM) has changed due to increased awareness and availability of advanced diagnostic tools. We aim to describe the temporal trends in age, gender and clinical characteristics at HCM diagnosis over >4 decades. METHODS We retrospectively analyzed records from the ongoing multinational SHaRe registry. Overall, 7,286 HCM patients diagnosed at an age ≥18 years between 1961 and 2019 were included in the analysis and divided into three eras of diagnosis (2010). RESULTS Age at diagnosis increased markedly over time (40±14 vs. 47±15 vs. 51±16 years, p30 mmHg: 31.9% vs. 39.3% vs. 39.0%, p=0.001). Consistent with decreasing phenotypic severity, yield of pathogenic/likely-pathogenic variants at genetic testing decreased over time (57.7% vs. 45.6% vs. 38.4%, p

IMPORTANCE: Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals to long-term adverse outcomes is still unresolved. OBJECTIVE: To describe the association of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) with long-term outcomes in patients with HCM in terms of overall disease progression, heart failure symptoms, and arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, retrospective data were analyzed from the ongoing prospective Sarcomeric Human Cardiomyopathy Registry, an international database created by 8 high-volume HCM centers that includes more than 6000 patients who have been observed longitudinally for decades. Records from database inception up to the first quarter of 2018 were analyzed. Patients were divided into 3 groups according to BMI class (normal weight group, 30). Patients with 1 or more follow-up visits were included in the analysis. Data were analyzed from April to October 2018. EXPOSURES: Association of baseline BMI with outcome was assessed. MAIN OUTCOME AND MEASURES: Outcome was measured against overall and cardiovascular mortality, a heart failure outcome (ejection fraction less than 35%, New York Heart Association class III/IV symptoms, cardiac transplant, or assist device implantation), a ventricular arrhythmic outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator therapy), and an overall composite outcome (first occurrence of any component of the ventricular arrhythmic or heart failure composite end point, all-cause mortality, atrial fibrillation, or stroke). RESULTS: Of the 3282 included patients, 2019 (61.5%) were male, and the mean (SD) age at diagnosis was 47 (15) years. These patients were observed for a median (interquartile range) of 6.8 (3.3-13.3) years. There were 962 patients in the normal weight group (29.3%), 1280 patients in the preobesity group (39.0%), and 1040 patients in the obesity group (31.7%). Patients with obesity were more symptomatic (New York Heart Association class of III/IV: normal weight, 87 [9.0%]; preobesity, 138 [10.8%]; obesity, 215 [20.7%]; P

BACKGROUND: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries. OBJECTIVES: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data. METHODS: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis. RESULTS: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion. CONCLUSIONS: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers.

Alexander disease is a leukodystrophy caused by dominant missense mutations in the gene encoding the glial fibrillary acidic protein. Individuals with this disorder often present with a typical neuroradiologic pattern including white matter abnormalities with brainstem involvement, selective contrast enhancement, and structural changes to the basal ganglia/thalamus. In rare cases, focal lesions have been seen and cause concern for primary malignancies. Here the authors present an infant initially diagnosed with a chiasmatic astrocytoma that was later identified as having glial fibrillary acidic protein mutation-confirmed Alexander disease. Pathologic and radiologic considerations that were helpful in arriving at the correct diagnosis are discussed.

Headache is a frequent symptom of lesions in the paranasal sinuses. Although some inflammatory symptoms are suggestive of pathologies of the paranasal sinuses, occasional headache is sometimes the major presenting symptom. In a retrospective study, we examined the chart histories of 36 patients presenting for treatment at our hospital from 1 January 1992 to 30 June 2001 who were diagnosed as having pathologies of the paranasal sinuses with the primary symptom being headache. All patients had been evaluated with complete otolaryngological and neurological examinations, diagnostic nasal endoscopy, and sinus computed tomographic (CT) scans. Sinus surgery was arranged after failure in performing appropriate medical treatment. Among the 36 patients, 33 showed significant improvement after sinus operation (92%). A paranasal sinus aetiology of headache is an important factor in the differential diagnosis of chronic headache. Those patients who are clinically suspected of having headaches arising from paranasal sinus pathology should receive comprehensive otorhinolaryngological examination and evaluation. Nasal endoscopy and sinus CT scans are good diagnostic tools. Surgical management may be beneficial in those for whom medical treatment fails to resolve the problem.

Background:Synovial sarcoma is a high-grade, soft tissue, malignant disease associated with poor outcome. Typically, synovial sarcoma involves the extremities, with less than 10 per cent of cases occurring in the head and neck region. Synovial sarcoma of the paranasal sinuses is a rare entity. This paper presents a case of an elderly patient with synovial sarcoma of the ethmoidal sinus.Case report:An 80-year-old woman who had right epistaxis underwent nasal endoscopy and biopsy. The pathology indicated synovial sarcoma and the patient underwent endoscopic excision of the tumour.Conclusion:Synovial sarcoma of the ethmoidal sinus is very rare. Patients should undergo excision of the tumour with post-operative radiotherapy. However, the prognosis remains poor and usually the patient succumbs to death within a year.

Headache associated with acute sinusitis is a widely accepted entity; diagnosis can be made by the associated nasal symptoms and computed tomography (CT) or endoscopic findings. However, chronic sinusitis as a cause of headache or facial pain is still controversial. In a few cases with sinus headaches may not necessarily present with a typical sinusitis history. Thus, referred headache of rhinogenic origin, in the absence of sinonasal symptoms, usually delays its diagnosis. Here we report two patients who presented with primary headache syndrome without significant nasal or sinus symptoms and who failed to respond to medical therapy. Case reports

The literature has shown that most immigrants reported a negative experience with their career in their newly adopted countries. In particular, they complained of loss in income and status, especially for those from non-English speaking countries. The Social Psychology literature has been shown that ethnic identity can influence an immigrant's perception of the fairness of organizational recruitment and job acceptance intention. However, little is known of the impact of immigrant's ethnic identity and how this impacts on their career experience. This is the subject of the current paper as we draw upon the literature on ethnic identity and social cognition career theory to examine the career experience 196 `visible racial minority' individuals in Australia. These individuals were immigrants from Asia (first generation Asian Australians) and Asian-born Australians (second generation Asian Australians) in Australia.

Guanxi, or social connections, has received increasing attention in the literature as the Western world grapples with the complexity of doing business with China. However the concept is often oversimplified in Western writings on business ethics. Networking and connections are seen as a business necessity, but on the other hand guanxi has been associated with corruption and calculative means of doing business. This study examines different dimensions of guanxi and their relationship to traditional vs modern value orientations. The study finds guanxi comprises two dimensions, one representing traditional Chinese values of reciprocity and face and the other a more modern networking style not dissimilar to that emphasised in the West. The need for a multi-dimensional approach to Guanxi is emphasised and discussed. Guanxi is a Chinese word literally translated to mean `social connections, and regarded as a key determinant to business success in modern Chinese society, particularly mainland China (Luo, 2000; Leung, Wong & Wong, 1996). Since the open-door policy was introduced in 1978, China began to change from a planned economy to a market-oriented system. In the face of increasing business contact between mainland Chinese and foreigners in the late 1970s, the word `guanxi has become popular business jargon in English (Gold ,Guthrie, & Wank, 2002). Nowadays, guanxi is used by Chinese and non-Chinese speakers to mean a mainland Chinese way of networking. Guanxi is different from the western approach of networking although they share some similarities. While they both are concerned about `knowing the right person, Chinese guanxi has a uniquely Chinese dimension of `reciprocity. Given the word `guanxi was not found in the old Chinese dictionary, some scholars argue that the concept of guanxi was a `new thing emerging in the late Cultural Revolution (1966-1976) and prospering in the economic reform period

Guanxi, or social connections, has received increasing attention in the literature as the Western world grapples with the complexity of doing business with China. But is guanxi a good or a bad thing? Networking and connections are seen as a business necessity, but on the other hand guanxi is often associated with corruption and calculative means of doing business. This study examines different dimensions of guanxi and their relationship to traditional vs modern value orientations. The study finds guanxi comprises two dimensions, one representing traditional Chinese values of reciprocity and face and the other a more modern networking style not dissimilar to that emphasised in the West. Relationships between dimensions of guanxi orientation and individual values and Westernisation are reported.

The importance of personal connections and relationships, or guanxi , when doing business with the Chinese is widely acknowledged amongst Western academics and business managers alike. However, aspects of guanxi related behaviours in the workplace are often misunderstood by Westerners with some going so far as to equate guanxi with forms of corruption. This study investigates the underlying modes of moral reasoning in ethical decisions relating to aspects of guanxi, amongst Hong Kong managers. Managers ethical judgements and underlying moral reasoning relating to a series of guanxi related behaviours, were recorded. Content analysis yielded categories that correspond with categories of moral reasoning described in Kohlberg s (1969) model. As hypothesised, it was found that harsher ethical evaluations of guanxi-related behaviours were positively correlated with the stage of moral reasoning. The most common types of reasoning were those corresponding to Kohlberg s stages four and five which relate to moral reasoning based on law and order, and on reason rather than emotion. Stage six, concerned with universal moral principles, was utilized considerably less than other stages. This finding supports the literature on ethical ideology across countries and cultures whereby Eastern cultures are generally found to be more relativistic or less universal than their Western counterparts.

Societal consciousness has shifted from national to international and global spheres, and the world is increasingly perceived as one place. Many sport organisations now find that they are under increasing pressure to engage in globally benchmarked sustainable management systems and processes, across all functional areas from finance to HRM. Some sport organisations have used aspects of the globalisation process to create new opportunities for expansion and growth, while others have been reluctant or resistant to externally instigated change. We assessed the adoption of "best practice" HRM practices in a range of amateur and professional sport organisations to see how they were reacting to these convergence pressures. This issue fits in the wider convergence-divergence debate that has been the concern of many cross-cultural researchers. Our empirical results indicate that while government policy has urged movement to a universally derived system of HRM processes, few sport organisations have adopted a formal HRM strategy and HR practices are widely variable across organisations.

OBJECTIVES: We sought to further define the role of sarcomere mutations in dilated cardiomyopathy (DCM) and associated clinical phenotypes. BACKGROUND: Mutations in several contractile proteins contribute to DCM, but definitive evidence for the roles of most sarcomere genes remains limited by the lack of robust genetic support. METHODS: Direct sequencing of 6 sarcomere genes was performed on 334 probands with DCM. A novel D230N missense mutation in the gene encoding alpha-tropomyosin (TPM1) was identified. Functional assessment was performed by the use of an in vitro reconstituted sarcomere complex to evaluate ATPase regulation and Ca(2+) affinity as correlates of contractility. RESULTS: TPM1 D230N segregated with DCM in 2 large unrelated families. This mutation altered an evolutionarily conserved residue and was absent in >1,000 control chromosomes. In vitro studies demonstrated major inhibitory effects on sarcomere function with reduced Ca(2+) sensitivity, maximum activation, and Ca(2+) affinity compared with wild-type TPM1. Clinical manifestations ranged from decompensated heart failure or sudden death in those presenting early in life to asymptomatic left ventricular dysfunction in those diagnosed during adulthood. Notably, several affected infants had remarkable improvement. CONCLUSIONS: Genetic segregation in 2 unrelated families and functional analyses conclusively establish a pathogenic role for TPM1 mutations in DCM. In vitro results demonstrate contrasting effects of DCM and hypertrophic cardiomyopathy mutations in TPM1, suggesting that specific functional consequences shape cardiac remodeling. Along with previous reports, our data support a distinctive, age-dependent phenotype with sarcomere-associated DCM where presentation early in life is associated with severe, sometimes lethal, disease. These observations have implications for the management of familial DCM.

COVID-19; SARS-CoV-2 infection; Heart failure COVID-19; Infección por SARS-CoV-2; Insuficiencia cardiaca COVID-19; Infecció per SARS-CoV-2; Insuficiència cardíaca Aims To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Methods and results Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12–4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75–9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16–26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20–49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98–2.91, P = 0.0600). Conclusions Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality. The project was funded by a grant from the Instituto de Salud Carlos III (ICSIII, COV20 00420). We should state that the SHaRe registry has been supported by an unrestricted grant from MyoKardia/Bristol Myers Squibb.

Dilated cardiomyopathy and hypertrophic cardiomyopathy arise from mutations in many genes. TTN, the gene encoding the sarcomere protein titin, has been insufficiently analyzed for cardiomyopathy mutations because of its enormous size.We analyzed TTN in 312 subjects with dilated cardiomyopathy, 231 subjects with hypertrophic cardiomyopathy, and 249 controls by using next-generation or dideoxy sequencing. We evaluated deleterious variants for cosegregation in families and assessed clinical characteristics.We identified 72 unique mutations (25 nonsense, 23 frameshift, 23 splicing, and 1 large tandem insertion) that altered full-length titin. Among subjects studied by means of next-generation sequencing, the frequency of TTN mutations was significantly higher among subjects with dilated cardiomyopathy (54 of 203 [27%]) than among subjects with hypertrophic cardiomyopathy (3 of 231 [1%], P=3×10(-16)) or controls (7 of 249 [3%], P=9×10(-14)). TTN mutations cosegregated with dilated cardiomyopathy in families (combined lod score, 11.1) with high (95%) observed penetrance after the age of 40 years. Mutations associated with dilated cardiomyopathy were overrepresented in the titin A-band but were absent from the Z-disk and M-band regions of titin (P≤0.01 for all comparisons). Overall, the rates of cardiac outcomes were similar in subjects with and those without TTN mutations, but adverse events occurred earlier in male mutation carriers than in female carriers (P=4×10(-5)).TTN truncating mutations are a common cause of dilated cardiomyopathy, occurring in approximately 25% of familial cases of idiopathic dilated cardiomyopathy and in 18% of sporadic cases. Incorporation of sequencing approaches that detect TTN truncations into genetic testing for dilated cardiomyopathy should substantially increase test sensitivity, thereby allowing earlier diagnosis and therapeutic intervention for many patients with dilated cardiomyopathy. Defining the functional effects of TTN truncating mutations should improve our understanding of the pathophysiology of dilated cardiomyopathy. (Funded by the Howard Hughes Medical Institute and others.).