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Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK-274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post-dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated.

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ−5D−3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively, mean difference: −12.4, p &lt, 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer&mdash, particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. Participants completed the EORTC QLQ-C30, EQ-5D-3L, PEmb-QoL, and VEINES-QOL/Sym questionnaires. Statistically significant and clinically relevant differences in terms of global health status were examined. Between 2015 and 2018, we enrolled 425 patients (128 cases and 297 controls, mean age: 60.2 &plusmn, 18.4 years). The most common malignancies were gastrointestinal (23.5%) and lung (19.8%) tumors. We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77, mean difference: &minus, 0.22) and EORTC QLQ-C30 (47.7 versus 58.4, 10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23, 21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7, 9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.

Noonan syndrome with multiple giant cell lesions (NS/MGCLS) is a term used to describe a subgroup of people with Noonan syndrome, a rare condition with phenotypic overlap with NS. Once thought to be a specific and separate entity, it is now suggested to be a variant of the NS spectrum. Here we report a 22-year-old patient misdiagnosed as having Rubinstein-Taybi syndrome (microcephaly, congenital heart disease, ventricular septal defect, cryptorchidism, pterygium coli, inguinal hernia, and short stature and neck). He had multiple dental retentions; therefore, a cone beam computed tomography was requested, which showed multiples radiolucent lesions of both sides of the jaw. An excisional biopsy of larger lesion was performed, and the results indicated giant cell granuloma. Patient was referred to the Genetics department because of suspicion of Noonan syndrome, which was confirmed after molecular study. Postoperative control shows bone formation in treated lesion on the right side and growth of the lesion on the left side.

The terrorist attacks of September 11th, 2001 affected the U.S. airline industry more than almost any other industry. Certain of these companies emerged successful, however, and demonstrated remarkable resilience while others languished. This investigation identifies the reasons why some airline companies recovered successfully after the attacks while others struggled. Evidence is provided that layoffs after the crisis, while intended to foster recovery, instead inhibited recovery throughout the four years after the crisis. But layoffs after the crisis were strongly correlated with the lack of financial reserves and the lack of a viable business model prior to the crisis. Digging deeper, we find that having a viable business model itself depended on the extent to which positive employee relationships had been achieved and maintained over the long term. One implication of our findings is that layoffs, while reducing costs in the short term, may also undermine the positive relationships that are critical for achieving lasting recovery.

The present paper structurally estimates the impact of increased variety in the EU and Asia over the period from 1989 to 2009. Using the most disaggregated import data available, we document that the number of varieties imported by the EU, defined as the number of import categories multiplied by the average number of source countries for each category, quadrupled, whereas it sextupled in Asia. About half of this increase was due to increases in the number of categories and half due to a doubling of the number of countries from which the EU and Asia imported each good. Using the Feenstra's (1994) methodology we estimate 35,000 elasticities and then construct an aggregate price index that is robust to common changes in quality variation, the arbitrary splitting of categories, the introduction of new goods, and other data problems. After reconstructing the EU and Asia import price indices, we found that the price of the EU imports has been falling at a rate 1.24 percent per year faster than one would have thought without taking new varieties into account. The variety gains for Asia are even higher - 2.69 percent per year.

This paper estimates the economic contributions of ATM to GDP and to employment in selected countries, as well as to provide some measures of ATM-related investment and economic productivity. Its focus, driven in part by availability of data, is on the European and North American economies. Incomplete information and estimates along parallel lines are also provided for small groups of States in Central and South America, South Asia and South Africa. The total impact of ATM (including direct, indirect and induced effects) on North American and European GDP in 2002 was estimated to be of the order of $22 billion, with total direct, indirect and induced employment at approximately 230,000 jobs. In these two regions, ATM capital investment amounted to approximately 20% ($2.6 billion) of revenue in 2002. Considering only direct values, worldwide ATM revenues were estimated to be in the range of $16-20 billion in 2002. Numerous other estimates of a similar nature are provided. Comparisons with other European data, confirm the view of ATM as a sector in which jobs have high skill content. Productivity appears to be comparable to that in other technologically advanced sectors of the economy. The findings of this study should be treated as preliminary, in view of data limitations and the diverse economic characteristics of the countries and regions examined.

Guinea pigs were maintained for various periods of time on low (0.5 mg/day), intermediate (20 mg/day), or high (100 and 500 mg/day) levels of dietary ascorbic acid. Animals in each experimental group were challenged with Candida al- bicans via cardiac injection, and the course of infection in the kidneys was assessed. The results show that the animals receiving only 0.5 mg of ascorbic acid per day were significantly more susceptible to the infection than animals maintained on any higher level of dietary ascorbic acid. The greater susceptibility of the guinea pigs in the 0.5- mg level group was evident, however, only during "early" stages of the infection (until about day 3). Guinea pigs receiving high levels of dietary ascorbic acid were no more resistant at any time after infection, or with any challenge dose, than those receiving an intermediate dietary level. Although these data suggest that vitamin C may be involved in resistance to candidiasis, tissue levels of ascorbic acid do not change sig nificantly with time after infection. These results indicate that low levels of dietary ascorbic acid increase susceptibility to candidiasis, yet high (or "megadose") levels of dietary vitamin C do not show any effect on resistance to this microorganism. J. Nutr. 113: 178-183, 1983.

Infections with Candida albicans are associated with a depressed immune response. The immunological profile present during candidiasis is extremely complex. Certain individuals with a congenital defect in the development of a normal cellular immune system are frequently the subject of clinical Candida disease involving mucocutaneous tissues (reviewed in 1). On the other hand, disseminated candidiasis is frequently encountered in individuals suffering with polymorphonuclear leukocyte function such as chronic granulomatous disease, myeloperoxidase deficiency, or Chediak-Higashi Syndrome (2,3,4). Individuals who manifest both mucocutaneous and disseminated forms of candidiasis are rare. The mode of resistance against these two forms of candidiasis presents a paradox since immune mechanisms effective in the first case apparently do not operate in the other.

This original collection examines the managerial and organizational implications of international terrorism and threats to security. When Islamic terrorists flew hijacked airplanes into the World Trade Center on 9/11, it changed much of the world forever. The number of deaths and the financial losses resulting from the attack was unprecedented. 9/11 highlighted how risky life in organizations had become.