Age specific trends in asthma mortality in England and Wales, 1983-95: results of an observational study.

OBJECTIVE: To determine trends in asthma mortality by age group in England and Wales during 1983-95. DESIGN: Observational study. SETTING: England and Wales. SUBJECTS: All deaths classified as having an underlying cause of asthma registered from 1 January 1983 to 31 December 1995. MAIN OUTCOME MEASURE: Time trends for age specific asthma deaths. RESULTS: Deaths in the age group 5-14 years showed an irregular downward trend during 1983-95; deaths in the age groups 15-44, 45-64, and 65-74 years peaked before 1989 and then showed a downward trend; and deaths in the age group 75-84 years peaked between 1988 and 1993 and subsequently dropped. Trends were: age group 5-14 years, 6% (95% confidence interval 3% to 9%); 15-44 years, 6% (5% to 7%); 45-64 years, 5% (4% to 6%); 65-74 years, 2% (1% to 3%). Deaths in the 75-84 and 85 and over categories plateaued. CONCLUSIONS: There are downward trends in asthma mortality in Britain, which may be due to increased use of prophylactic treatment.     

Health-related quality of life and metabolic control in children with type 1 diabetes mellitus in Bosnia and Herzegovina

The primary objective of the study was to examine the relationship between generic and disease-specific HRQOL scores and metabolic control in children with Type 1 Diabetes Mellitus (T1DM). This cross-sectional study included 65 consecutive children between ages 5 and 18 years with T1DM. According to their values of glycosylated hemoglobin (HbA(1C)), the children were assigned to one of two groups. In Group 1 (N = 21) were the children with HbA(1C) values < 8% (good to moderate metabolic control) and Group 2 (N = 44) were children with > 8% (poor metabolic control). To evaluate generic and disease-specific HRQOL scores in children with T1DM in relation to metabolic control, we used the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Diabetes Module. The patients in Group 1, by pediatric patient self-report and parent proxy-report, had statistically better disease-specific HRQOL scores on the diabetes symptoms, treatment barriers, treatment adherence and worry domains in comparison with Group 2. We also found significant correlations between the total generic HRQOL scores and HbA(1C) for both parent proxy-reports' Spearman's coefficient of rank correlation rho = -0.257; p = 0.0412 and pediatric patients' Spearman's coefficient of rank correlation rho = -0.269; p = 0.0313. The current findings suggest that poor glycemic control in children with T1DM is associated with lower generic and disease-specific HRQOL scores in developing and transitional countries.     

脐带血干细胞移植治疗非恶性血液病进展

异基因造血干细胞移植（allo-HSCT）是治愈多种非恶性病的有效方法。脐带血干细胞（UCB）具有免疫原性低、人类白细胞抗原不合耐受性好、移植物抗宿主反应发生率低以及获取相对快捷等特点,可作为非恶性血液疾病患者allo-HSCT的来源。本文简要综述脐血干细胞移植在原发性免疫缺陷病、遗传性骨髓衰竭、遗传代谢病以及自身免疫性疾病等非恶性血液疾病的治疗效果。     

LY2405319, an Engineered FGF21 Variant,Improves the Metabolic Status of Diabetic Monkeys

Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that represents a promising target for the treatment of several metabolic diseases. Administration of recombinant wild type FGF21 to diabetic animals leads to a dramatic improvement in glycaemia and ameliorates other systemic measures of metabolic health. Here we report the pharmacologic outcomes observed in non-human primates upon administration of a recently described FGF21 analogue, LY2405319 (LY). Diabetic rhesus monkeys were treated subcutaneously with LY once daily for a period of seven weeks. The doses of LY used were 3, 9 and 50 mg/kg each delivered in an escalating fashion with washout measurements taken at 2, 4, 6 and 8 weeks following the final LY dose. LY therapy led to a dramatic and rapid lowering of several important metabolic parameters including glucose, body weight, insulin, cholesterol and triglyceride levels at all doses tested. In addition, we observed favorable changes in circulating profiles of adipokines, with increased adiponectin and reduced leptin indicative of direct FGF21 action on adipose tissue. Importantly, and for the first time we show that FGF21 based therapy has metabolic efficacy in an animal with late stage diabetes. While the glycemic efficacy of LY in this animal was partially attenuated its lipid lowering effect was fully preserved suggesting that FGF21 may be a viable treatment option even in patients with advanced disease progression. These findings support continued exploration of the FGF21 pathway for the treatment of metabolic disease.     

食管癌术后并发症及其处理

食管癌是我国一种常见的消化道恶性肿瘤,居世界癌症死因第7位,中国癌症死因第4位。其中以中段鳞状细胞癌多见,临床表现以晚期进行性吞咽困难为主,确诊主要以胃镜病理活检为金标准,其治疗方法主要有手术、放疗、化疗及分子靶向治疗等。但目前治疗上仍然以手术为主,术前术后放化疗为辅。然而,随着手术在食管癌治疗中适应症的不断扩大、根治性手术淋巴结的扩大清扫及拥有基础疾病高龄患者的增多,术后并发症的发生率不可避免的随之增加。本文将重点阐述吻合口瘘、吻合口狭窄、呼吸及心血管并发症、乳糜胸、胃排空障碍、膈疝、喉返神经损伤及单纯脓胸、严重腹泻、呕血等食管癌术后常见、严重并发症的病因、临床表现与诊断、治疗及其预防。通过对食管癌术后并发症的充分认识及有效预防,从而对食管癌手术成功率及患者术后生存质量的提高、肿瘤预后的改善起到了重要作用。     

尤瑞克林联合静脉溶栓治疗急性脑梗塞的临床疗效及对血浆血小板、D-D、Fg水平的影响

目的:探讨尤瑞克林联合静脉溶栓治疗急性脑梗塞的临床疗效及对血浆血小板、D-二聚体(D-D)、纤维蛋白原(Fg)水平的影响。方法:选择2015年5月至2018年5月我院接诊的急性脑梗塞患者65例作为研究对象,根据随机数表法分为观察组(n=35)和对照组(n=30)。对照组采用静脉溶栓治疗,观察组采用尤瑞克林联合静脉溶栓治疗。比较两组治疗后的临床疗效,治疗前后血浆血小板、D-D、Fg、美国国立卫生研究院卒中量表(NIHSS)评分、改良Barthel指数评定量表(MBI)水平的变化及不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率为94.29%,显著高于对照组(73.33%,P0.05)。两组患者治疗前血浆血小板、D-D、Fg水平、NIHSS、MBI评分比较差异均无统计学意义(P0.05);治疗后,两组患者血浆血小板、D-D、Fg水平及NIHSS评分均较治疗前明显降低,且观察组患者以上指标均显著低于对照组(P0.05);两组患者治疗治疗后MBI评分均较治疗前显著升高,且观察组MBI评分显著高于对照组(P0.05)。两组患者不良反应总发生率分别为2.86%、13.33%,组间比较差异无统计学意义(P0.05)。结论:尤瑞克林联合静脉溶栓治疗急性脑梗塞患者的临床效果显著优于单用静脉溶栓治疗,这可能与其更有效改善改善患者血浆血小板、D-D、Fg水平有关。     

Analysis of diversity of autosomal-recessive diseases in Russian populations]

The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected subjects was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1:50,000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1:877,483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (Fst) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (Fst) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift.     

LEMOXINET: Lite ensemble MobileNetV2 and Xception models to predict plant disease

Plant diseases play a significant role in agricultural production, in which early detection of plant diseases is deemed an essential task. Current computational intelligence and computer vision methods have been promising to improve disease diagnosis. Convolutional Neural Networks (CNN) models are capable of detecting plant diseases in an agricultural field and plantation leaf images. MobileNetV2 refers to an appropriate CNN model for mobile devices with subordinate parameters and model file sizes. However, the effectiveness of MobileNetV2 requires improvement to capture more critical features. Xception refers to the extension of InceptionV3 with fewer and excellent parameters in extracting features. This research suggests an ensemble of MobileNetV2 and Xception by concatenating the extracted features to improve plant disease detection performance. This study indicated that MobileNetV2, Xception, and ensemble model achieved 97.32%, 98.30%, and 99.10% accuracy when considering the entire Plant Village dataset. Particularly, MobileNetV2 and Xception models' accuracy improved by 1.8% and 0.8%, respectively. In addition, our model captures 99.52% of all metric scores in the user-defined dataset. Our model indicated better performance than the seven state-of-the-art CNN models, both individually and in ensemble design. It can be integrated with mobile devices, providing fewer parameters and model file size than an ensemble of MobileNetV2 with InceptionResnetV2, VGG19, and VGG16.     

氟哌啶醇与奥氮平治疗精神分裂症的疗效对比探究

目的：对比分析氟哌啶醇与奥氮平治疗精神分裂症的临床疗效。方法：回顾性分析我院2008年4月-2011年12月收治的精神分裂症患者62例,通过随机数法将其分为两组,其中31例为氟哌啶醇组,剩余31例为奥氮平组,比较两组服药后的临床疗效以及药物不良反应情况。结果：6周后氟哌啶醇组和奥氮平组的PANSS总分均明显低于治疗前PANSS总分,组间比较,治疗3周、6周后奥氮平组PANSS总分均低于氟哌啶醇组,并且同时段奥氮平组的减分率明显高于氟哌啶醇组,差异均具有统计学意义（P〈0.05）。氟哌啶醇组的心电图异常例数和静坐不能例数明显高于奥氮平组,差异均具有统计学意义。而氟哌啶醇组不良反应发生率为48.39%,奥氮平组不良反应发生率为51.61%,差异无统计学意义。奥氮平组治疗6周后TG含量明显高于治疗前,并且两组的BMI也明显高于治疗前,差异均具有统计学意义（P〈0.05）。结论：氟哌啶醇与奥氮平在治疗精神分裂症上均有较好疗效,不良反应发生率也相似,而奥氮平改善症状较好,同时对心脏影响小,但是比氟哌啶醇易引起TG和BMI的增高,临床上需要根据患者身体条件选择药物,提高其安全性。     

A novel class of tests for the detection of mitochondrial DNA-mutation involvement in diseases

We develop a novel class of tests to detect mitochondrial DNA (mtDNA)-mutation involvement in complex diseases by the study of affected pedigree members. For a pedigree, affected individuals are first considered and are then connected through their relatives. We construct a reduced pedigree from an original pedigree. Each configuration of a reduced pedigree is given a score, with high scores given to configurations that are consistent with mtDNA-mutation involvement and low scores given to configurations that are not consistent with mtDNA-mutation involvement. For many pedigrees, the weighted sum of scores of the pedigrees is calculated. The tests are formed by comparing the observed score with the expected score under the null hypothesis that only nuclear autosomal mutations are involved. We study the optimality of score functions and weights under the heterogeneity model without phenocopies. We also develop a method to estimate the contribution that mtDNA mutations make if they are involved under a heterogeneity model. Finally, we apply our methods to three data sets: Leber hereditary optic neuropathy, a disease that has been proved to be caused by mtDNA mutations; non-insulin-dependent diabetes mellitus (NIDDM); and hypertension (HTN). We find evidence of mtDNA-mutation involvement in all three diseases. The estimated fraction of patients with NIDDM due to mtDNA-mutation involvement is 22% (95% confidence interval [CI] 6%-38%). The fraction of patients with HTN potentially due to mtDNA-mutation involvement is estimated at 55% (95% CI 45%-65%).     

Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances efficacy in an in vivo model of arthritis

Despite the clinical success of anti-tumor necrosis factor (TNF) therapies in the treatment of inflammatory conditions such as rheumatoid arthritis, Crohn disease and psoriasis, full control of the diseases only occurs in a subset of patients and there is a need for new therapeutics with improved efficacy against broader patient populations. One possible approach is to combine biological therapeutics, but both the cost of the therapeutics and the potential for additional toxicities needs to be considered. In addition to the various mediators of immune and inflammatory pathways, angiogenesis is reported to contribute substantially to the overall pathogenesis of inflammatory diseases. The combination of an anti-angiogenic agent with anti-TNF into one molecule could be more efficacious without the risk of severe immunosuppression. To evaluate this approach with our Zybody technology, we generated bispecific antibodies that contain an Ang2 targeting peptide genetically fused to the anti-TNF antibody adalimumab (Humira®). The bispecific molecules retain the binding and functional characteristics of the anti-TNF antibody, but with additional activity that neutralizes Ang2. In a TNF transgenic mouse model of arthritis, the bispecific anti-TNF-Ang2 molecules showed a dose-dependent reduction in both clinical symptoms and histological scores that were significantly better than that achieved by adalimumab alone.     

Tyrosinase Inhibitory and Anti-oxidative Effects of Lactic Acid Bacteria Isolated from Dairy Cow Feces

Overproduction and accumulation of melanin cause a number of skin diseases. The inhibitors of tyrosinase are important for the treatment of skin diseases associated with hyper-pigmentation after UV exposure and application in cosmetics for whitening and depigmentation. Reactive oxygen species (ROS) including hydrogen peroxide are generated by chemical substances and metabolic intermediates and cause various diseases including cancer and heart diseases. We have isolated four different lactic acid bacteria (LAB) strains from dairy cow feces and investigated the tyrosinase inhibition and anti-oxidative effects of culture filtrates prepared from the isolated bacteria, which are designated as EA3, EB2, PC2, and PD3. To investigate optimal culture conditions isolated LAB strains, the measurements of tyrosinase inhibitory and anti-oxidative activities were performed. The results of tyrosinase inhibitory activities revealed that Enterococcus sp. EA3 showed about 65% at culture conditions (14 h, 30 °C, pH 8, and 0% NaCl), Enterococcus sp. EB2 about 65% at culture conditions (12 h, 30 °C, pH 9, and 0% NaCl), Pediococcus sp. PC2 about 80% at culture conditions (20 h, 30 °C, pH 6, and 0% NaCl), and Pediococcus sp. PD3 about 80% at culture conditions (20 h, 30 °C, pH 8, and 0% NaCl), respectively. In addition, anti-oxidative activities against four different LAB strains showed approximately more than 30% at optimal conditions for the measurements of tyrosinase inhibitory activities. From the results, we have suggested that the isolated four LAB strains could be useful for a potential agent for developing anti-oxidants and tyrosinase inhibitors.     

Study of some epidemiological aspects of 253 cases of cryptococcosis.

Some epidemiological characteristics of 253 cases of cryptococcosis (CRY) diagnosed between 1981 and 1993 in the Mu?iz Hospital (MH) of Buenos Aires City, were studied. The incidence of CRY associated with AIDS (CRY+AIDS) in the MH during 1983-1993, could be divided into 3 periods: between 1983 and 1988 1-3 cases a year were diagnosed; during 1989-91, the number of cases dopubled annually and in 1992-93 the annual increment was lower. CRY associated with predisposing causes other than AIDS (CRY+non AIDS) exhibited an annual incidence of 0-3 cases during the whole period studied. CRY was more frequent in males (86%). The difference between sexes was more evident in CRY+AIDS patients (88% males) than CRY+non AIDS ones (65% males). The median age (MA) of the studied population was 28 (range 10-71) years; 27 (10-48) in women and 29 (17-71) in men. CRY+AIDS and CRY+non AIDS patients exhibited a MA of 29 (17-51) and 40 years (10-71), respectively. AIDS was the predisposing factor in 92% of patients; 65% of them were intravenous drug abusers and 22% homosexual males, with a MA of 27 (17-40) and 33 (23-55) years, respectively. Cryptococcus neoformans var. neoformans was isolated from all CRY+AIDS and 79% of CRY+non AIDS patients and the gattii variety (Serotype B) produced 4 (21%) cases of CRY+non AIDS.     

凝结芽孢杆菌活菌片对 腹泻型肠易激综合征患者的治疗

目的观察和评价凝结芽孢杆菌活菌片(商品名:爽舒宝)对腹泻型肠易激综合征患者的临床疗效。方法将100例腹泻型肠易激综合征患者随机分为3组,其中爽舒宝治疗组32例,马来酸曲美布汀治疗组35例,联合治疗组33例。3组患者疗程均为60d,记录3组患者腹痛、腹泻、排便异常等症状的变化。结果在近期疗效方面,联合治疗组有效率(87.87%)高于爽舒宝治疗组(75.00%),而这两组的有效率均高于马来酸曲美布汀治疗组(51.43%)。在远期疗效方面,爽舒宝治疗组患者有效率(100.00%)和联合治疗组(100.00%)之间无显著差异,而这两组的有效率均高于马来酸曲美布汀治疗组(74.29%)。治疗结束后,3组患者大便次数、腹痛、大便性状等各项症状体征积分均较治疗前显著降低(P0.05),其中联合治疗组患者治疗后各项症状体征积分与爽舒宝治疗组比较差异无统计学意义(P0.05),但均低于马来酸曲美布汀治疗组(P0.05)。结论凝结芽孢杆菌活菌片治疗腹泻型肠易激综合征疗效显著,值得在临床治疗中推广应用。     

肥大细胞增生症研究进展

肥大细胞增生症(mastocytosis)是由多种临床表现组成的一组疾病谱,其特征表现以肥大细胞在一个或多个器官异常浸润和积聚为主,常累及皮肤、消化道、骨髓、肝脾以及淋巴结,临床表现为皮肤瘙痒、潮红、恶心、呕吐、腹泻、腹痛等改变。针对存在以下情况需考虑本病:不明原因的溃疡或吸收不良;影像学检查发现骨骼扫描异常、肝脾肿大、淋巴结肿大;外周血异常;速发型过敏反应;或原因不明的低血压;一旦确定为肥大细胞增生症引起,应对疾病活动性、亚型和预后进行评估,并进行适当治疗;肥大细胞增多症根据临床表现、病理改变和预后分为7种不同类型,皮肤性及惰性系统性肥大细胞增多症预后较好,肥大细胞肉瘤预后最差。本文对肥大细胞增生症发病机制、临床特征、诊断、治疗及预后等方面的研究现状进行综述。     

Analysis of Diversity of Autosomal Recessive Diseases in Populations of Russia

The diversity of autosomal recessive (AR) diseases was studied in six Russian regions: the Kirov, Kostroma, and Bryansk oblasts; Adygea Republic; Krasnodar krai, and Marii El Republic (in the latter region, the Mari and Russian ethnic groups were studied separately). In total, more than 1.5 million people were studied. The spectrum of the AR diseases included 101 nosological forms; the total number of the affected was 942. For all diseases, the prevalence rate in the region where they were found and the mean prevalence rate in the total population studied were calculated. Only seven AR diseases had prevalence rates of 1 : 50000 or higher; however, this group contained about 50% of the patients. About half of the AR diseases (66) had an extremely low prevalence rate (1 : 877483). Eleven diseases exhibit local accumulation. Accumulation of some or other diseases was only observed in four out of seven populations studied (Marii El, Adygea, and the Kirov and Bryansk oblasts). To determine the cause of the local accumulation of some diseases in populations, correlation analysis of the dependence of accumulation of hereditary diseases on the genetic structure of the populations studied was performed. The accumulation coefficients for AR and autosomal dominant (AD) diseases and the mean values of random inbreeding (F _st) in individual districts were calculated for all populations studied. The coefficients of the Spearman rank correlation between the accumulation coefficient and random inbreeding (F _st) were 0.68 and 0.86 for the AD and AR diseases, respectively. The correlation between the accumulation of AD and AR diseases was 0.86. The relationships found indicate that the diversity of AD and AR diseases, as well as the genetic load, distinctly depended on the population genetic structure and were largely determined by genetic drift.     

Simultaneous targeting of TNF and Ang2 with a novel bispecific antibody enhances efficacy in an in vivo model of arthritis

Despite the clinical success of anti-tumor necrosis factor (TNF) therapies in the treatment of inflammatory conditions such as rheumatoid arthritis, Crohn disease and psoriasis, full control of the diseases only occurs in a subset of patients and there is a need for new therapeutics with improved efficacy against broader patient populations. One possible approach is to combine biological therapeutics, but both the cost of the therapeutics and the potential for additional toxicities needs to be considered. In addition to the various mediators of immune and inflammatory pathways, angiogenesis is reported to contribute substantially to the overall pathogenesis of inflammatory diseases. The combination of an anti-angiogenic agent with anti-TNF into one molecule could be more efficacious without the risk of severe immunosuppression. To evaluate this approach with our Zybody technology, we generated bispecific antibodies that contain an Ang2 targeting peptide genetically fused to the anti-TNF antibody adalimumab (Humira®). The bispecific molecules retain the binding and functional characteristics of the anti-TNF antibody, but with additional activity that neutralizes Ang2. In a TNF transgenic mouse model of arthritis, the bispecific anti-TNF-Ang2 molecules showed a dose-dependent reduction in both clinical symptoms and histological scores that were significantly better than that achieved by adalimumab alone.     

r-tpa合并甘露醇治疗血管壁病变性脑梗死的临床疗效分析

目的:观察r-tpa合并甘露醇治疗血管壁病变性脑梗死临床疗效。方法:将临床发病6 h以内的急性脑梗死患者随机分为治疗组与对照组,每组60例,治疗组用r-tpa合并甘露醇静脉滴注,对照组用川芎嗪注射液静脉滴注,对治疗组和对照组连续使用15天观察对照组和治疗组的临床疗效及神经功能恢复情况。结果:采用r-tpa合并甘露醇静脉滴注和川芎嗪静脉注射液疗效比较,治疗组总有效率93.33%,明显优于常规治疗组78.33%,两组差异有统计学意义(P0.05)。两组患者治疗后CSS评分均显著低于治疗前,且治疗组明显低于对照组(P0.05);两组患者治疗后ADL评分均显著高于治疗前,且治疗组明显高于对照组(P0.05)。结论:r-tpa合并甘露醇治疗血管壁病变性脑梗死临床疗效显著,且对6个小时内没有出血倾向的血管病变性脑梗死安全实用,患者后期恢复效果良好。     

The New Zealand Scincidae (Reptilia: Lacertilia); a taxonomic and zoogeographic study

Abstract

The mohua (or yellowhead, Mohoua ochrocephala) is an endangered hole‐nesting passerine which is now absent from >75% of its former range. This paper describes an 11 year monitoring programme, which was set up to survey 14 populations at 12 key sites throughout the range of the mohua, in order to document the pattern of population change and provide early warning of likely local extinctions. Between 1983 and 1993, one mohua population became extinct. Five of the 14 populations declined significantly, and three of these were on the verge of extinction by 1993. One population increased, and seven did not change significantly, although a declining trend was recorded at five of these. Six population crashes coincided with irruptions of stoats (Mustela erminea) following heavy beech (Nothofagus) seeding.     

Case report of a possible familial predisposition to metabolic bone disease in juvenile rhesus macaques

Deficiencies of dietary calcium and/or vitamin D will cause hypocalcaemia, leading to metabolic bone disease. The disease commonly affects young rapidly growing animals and this is a report of the condition in a colony of rhesus macaques (Macaca mulatta). A clinical problem of metabolic bone disease was seen in 1993, when it was treated and resolved satisfactorily. However it recurred in 1999 following changes in management and husbandry of the colony, at which time the clinical manifestations were more serious. The animals had bowed tibia, fibula, radius and ulna and enlarged epiphyses, were reluctant to climb and jump, had a 'hopping' gait and poor growth. The syndrome had a multifactorial aetiology involving a combination of staff and management changes, a borderline nutritional deficit, a lack of daylight for production of vitamin D, and a possible familial predisposition.