Photocrystallographic Studies on Transition Metal Nitrito Metastable Linkage Isomers: Manipulating the Metastable State.
The design of solid-state materials whose properties and functions can be manipulated in a controlled manner by the application of light is an important objective in modern materials chemistry. When the material changes property or function, it is helpful if a simple measurable response, such as a change in color, can be detected. Potential applications for such materials are wide ranging, from data storage to smart windows. With the growing emphasis on solid-state materials that have two or more accessible energy states and which exhibit bistability, attention has turned to transition metal complexes that contain ambidentate ligands that can switch between linkage isomeric forms when activated by light. Suitable ligands that show promise in this area include nitrosyls, nitro groups, and coordinated sulfur dioxide molecules, each of which can coordinate to a metal center in more than one bonding mode. A nitrosyl normally coordinates through its N atom (η1-NO) but when photoactivated can undergo isomerism and coordinate through its O atom (η1-ON). At a molecular level, converting between these two configurations can act as an "on/off" switch. The analysis of such materials has been aided by the development of photocrystallographic techniques, which allow the full three-dimensional structure of a single crystal of a complex, under photoactivation, to be determined, when it is in either a metastable or short-lived excited state. The technique effectively brings the dimension of "time" to the crystallographic experiment and brings us closer to being able to watch solid-state processes occur in real time. In this Account, we highlight the advances made in photocrystallography for studying solid-state, photoactivated linkage isomerism and describe the factors that favor the switching process and which allow complete switching between isomers. We demonstrate that control of temperature is key to achieving either a metastable state or an excited state with a specific lifetime. We draw our conclusions from published work on the formation of photoactivated metastable states for nitrosyl and sulfur dioxide complexes and from our own work on photoactivated switching between nitro and nitrito groups. We show that efficient switching between isomers is dependent on the wavelength of light used, on the temperature at which the experiment is carried out, on the flexibility of the crystal lattice, and on both the electronic and steric environment of the ambidentate ligand undergoing isomerism. We have designed and prepared a number of nitro/nitrito isomeric metal complexes that undergo reversible 100% conversion between the two forms at temperatures close to room temperature. Through our fine control over the generation of the metastable states, it should be possible to effectively "dial up" a suitable temperature to give a metastable or an excited state with a desired lifetime.


Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders: On the basis of information from a European multicenter registry.
Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%), and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine:L-leucine:L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine, and L-leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. In conclusion, while MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D, and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation.


Podocyte Senescence and Aging.
As the population in many industrial countries is aging, the risk, incidence, and prevalence of chronic kidney diseases (CKD) increases. In the kidney, advancing age results in a progressive decrease in nephron number and an increase in glomerulosclerosis. In this review, we focus on the impact of aging on glomerular podocytes, the post-mitotic epithelial cells critical for the normal integrity and function of the glomerular filtration barrier. The podocytes undergo senescence and transition to a senescent-associated secretory phenotype typified by the production and secretion of inflammatory cytokines that can influence neighboring glomerular cells by paracrine signaling. In addition to senescence, the aging podocyte phenotype is characterized by ultrastructural and functional changes, hypertrophy, cellular, oxidative and endoplasmic reticulum stress, reduced autophagy and increased expression of aging genes. This results in a reduced podocyte health-span and a shortened lifespan. Importantly, these changes in the pathways/processes characteristic of healthy podocytes aging are also often similar to pathways in the disease-induced injured podocyte. Finally, the better understanding of podocyte aging and senescence opens therapeutic options to slow the rate of podocyte aging and promote kidney health.


Association between sarcopenia and hearing thresholds in postmenopausal women.
Background: Given the association between metabolic disturbance and sarcopenia, sarcopenia may be intrinsically associated with the prevalence of HL. However, few studies describe the association between sarcopenia and HL. The aim of this study was to evaluate the clinical association between sarcopenia and HL in postmenopausal Korean women. Patients and Methods: A total of 4,038 women were ultimately included in this study. All participants were postmenopausal. Participants were divided into two groups based on criteria from the Foundation for the National Institute of Health Sarcopenia Project: a normal group (sarcopenia index ≥ 0.512) and a sarcopenia group (sarcopenia index < 0.512). Low-frequency (Low-Freq), mid-frequency (Mid-Freq), and high-frequency (High-Freq) values were obtained. The average hearing threshold (AHT) was calculated as the pure tone average at the 4 frequencies of 0.5 kHz, 1 kHz, 2 kHz, and 3 kHz. Mild HL was as an AHT of 24 to 40 dB; moderate-to-profound HL was defined as an AHT of 40 dB or greater. Results: Of the 4,038 participants, 272 (6.7%) were allocated to the sarcopenia group, leaving 3,766 (93.3%) in the normal group. The groups differed significantly in terms of having hypertension (775 [20.6%] vs. 108 [39.7%]; P < 0.001) or metabolic syndrome (817 [21.7%] vs. 110 [40.4%]; P < 0.001) in the normal and sarcopenia groups, respectively. Visceral fat area (cm3) in the normal and sarcopenia groups was 99.0 ± 21.9 cm3 and 117.0 ± 21.8 cm3 , respectively (P < 0.001). The hsCRP level was higher in the sarcopenia group than in the normal group. For univariate and multivariate analyses, all 4 hearing thresholds were higher in the sarcopenia group than in the normal group. In addition, linear regression analyses showed Low-Freq, Mid-Freq, and High-Freq to be inversely correlated with the sarcopenia index. The unadjusted OR for mild HL was 2.692 (95% CI, 1.963-3.692; P < 0.001) in the sarcopenia group relative to the normal group, with an adjusted OR of 1.584 (95% CI, 1.131-2.217; P = 0.007). The unadjusted OR for moderate-to-profound HL in the sarcopenia group relative to the normal group was 6.246 (95% CI, 4.530-8.612; P < 0.001); the adjusted OR was 2.667 (95% CI, 1.866-3.812; P < 0.001). Conclusion: Sarcopenia may be associated with HL. It may be beneficial to perform screening audiometry in patients with sarcopenia.


Alcohol marketing on YouTube: exploratory analysis of content adaptation to enhance user engagement in different national contexts.
We know little about how social media alcohol marketing is utilized for alcohol promotion in different national contexts. There does not appear to be any academic work on online exposure to alcohol marketing via social media in India, and most of the limited research in Australia has focused on Facebook. Hence, the present study extends previous research by investigating alcohol promotion conducted on an under-researched form of social media (YouTube) in two contrasting geographic contexts. This study examines and compares the types of strategies used by marketers on Indian and Australian alcohol brands with the greatest YouTube presence, and the extent to which users engage with these strategies. The 10 alcohol brands per country with the greatest YouTube presence were identified based on the number of 'subscriptions'. The number of videos, views per video, and the type of content within the videos were collected for each brand. The data were analyzed using an inductive coding approach, using NVivo 10. The targeted brands had gathered 98,881 subscriptions (Indian brands: n = 13,868; Australian brands: n = 85,013). The type of marketing strategies utilized by brands were a mix of those that differed by country (e.g. sexually suggestive content in India and posts related to the brand's tradition or heritage in Australia) and generic approaches (e.g. encouraging time- and event-specific drinking; demonstrations of food/cocktail recipes; camaraderie; competitions and prize draws; and brand sponsorship at music, sports, and fashion events). This cross-national comparison demonstrates that YouTube provides alcohol marketers with an advertising platform where they utilize tailored marketing approaches to cater to specific national contexts and develop content on the cultural meanings users invoke in their interactions with these strategies. Those exposed to alcohol marketing on YouTube are likely to include those under the legal drinking age.


Studies of Radioaerosol Deposition in the Respiratory Tract.
Deposition of aerosols in the respiratory tract can be quantitatively and qualitatively studied by scintigraphy. The most commonly used radionuclide for this purpose is technetium-99m. The effects of various factors on particle deposition have been investigated by using radiolabeled aerosols in the past decade. Most of these studies were in vivo but some were in vitro or ex vivo. The factors examined include particle size, formulation, inhaler design, inhalation flowrate, body posture, and gravity. They have been shown to influence pulmonary deposition, nasal high flow nebulization, and intranasal delivery. A thorough understanding of the various factors is required for the advancement of respiratory-drug delivery. Scintigraphy is a powerful technique that can assist in this regard.


Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein ε4 Children Exposed to Air Pollution.
Children's urban air pollution exposures result in systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most prevalent genetic risk for AD. We assessed whether APOE in healthy children modulates cognition, olfaction, and metabolic brain indices. The Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test were administered to 50 Mexico City Metropolitan Area children (13.4 ± 4.8 years, 28 APOE ε3 and 22 APOE ε4). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, and NAA/mI were calculated using proton magnetic resonance spectroscopy in the white matter of the frontal and parietal lobes, hippocampus, and pons. APOE ε4 versus ε3 children had a reduced NAA/Cr ratio in the right frontal white matter and decrements on attention, short-term memory, and below-average scores in Verbal and Full Scale IQ (>10 points). APOE modulated the group effects between WISC-R and left frontal and parietal white matter, and hippocampus metabolites. Soap was the predominantly failed odor in urban children and, in APOE ε4 versus ε3 carriers, strongly correlated with left hippocampus mI/Cr ratio. APOE modulates responses to air pollution in the developing brain. APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted environment. APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection and AD prevention.


Analyzing the equity of public primary care provision in Kenya: variation in facility characteristics by local poverty level.
Equitable access to health care is a key health systems goal, and is a particular concern in low-income countries. In Kenya, public facilities are an important resource for the poor, but little is known on the equity of service provision. This paper assesses whether poorer areas have poorer health services by investigating associations between public facility characteristics and the poverty level of the area in which the facility is located. Data on facility characteristics were collected from a nationally representative sample of public health centers and dispensaries across all 8 provinces in Kenya. A two-stage cluster randomized sampling process was used to select facilities. Univariate associations between facility characteristics and socioeconomic status (SES) of the area in which the facility was located were assessed using chi-squared tests, equity ratios and concentration indices. Indirectly standardized concentration indices were used to assess the influence of SES on facility inputs and service availability while controlling for facility type, province, and remoteness. For most indicators, we found no indication of variation by SES. The clear exceptions were electricity and laboratory services which showed evidence of pro-rich inequalities, with equity ratios of 3.16 and 3.43, concentration indices of 0.09 (p<0.01) and 0.05 (p=0.01), and indirectly standardized concentration ratios of 0.07 (p<0.01) and 0.05 (p=0.01). There were also some indications of pro-rich inequalities for availability of drugs and qualified staff. The lack of evidence of inequality for other indicators does not imply that availability of inputs and services was invariably high; for example, while availability was close to 90% for water supply and family planning services, under half of facilities offered delivery services or outreach. The paper shows how local area poverty data can be combined with national health facility surveys, providing a tool for policy makers to assess the equity of input and service availability. There was little evidence of inequalities for most inputs and services, with the clear exceptions of electricity and laboratory services. However, efforts are required to improve the availability of key inputs and services across public facilities in all areas, regardless of SES.


Axillary lymph node dose with tangential whole breast radiation in the prone versus supine position: a dosimetric study.
Prone breast positioning reduces skin reaction and heart and lung dose, but may also reduce radiation dose to axillary lymph nodes (ALNs). Women with early stage breast cancer treated with whole breast irradiation (WBI) in the prone position were identified. Patients treated in the supine position were matched for treating physician, laterality, and fractionation. Ipsilateral breast, tumor bed, and Level I, II, and III ALNs were contoured according to the RTOG breast atlas. Clips marking surgically removed sentinel lymph nodes (SLN)s were contoured. Treatment plans developed for each patient were retrospectively analyzed. V90% and V95% was calculated for each axillary level. When present, dose to axillary surgical clips was calculated. Treatment plans for 46 women (23 prone and 23 supine) were reviewed. The mean V90% and V95% of ALN Level I was significantly lower for patients treated in the prone position (21% and 14%, respectively) than in the supine position (50% and 37%, respectively) (p < 0.0001 and p < 0.0001, respectively). Generally, Level II & III ALNs received little dose in either position. Sentinel node biopsy clips were all contained within axillary Level I. The mean V95% of SLN clips was 47% for patients treated in the supine position and 0% for patients treated in the prone position (p < 0.0001). Mean V90% to SLN clips was 96% for women treated in the supine position but only 13% for women treated in the prone position. Standard tangential breast irradiation in the prone position results in substantially reduced dose to the Level I axilla as compared with treatment in the supine position. For women in whom axillary coverage is indicated such as those with positive sentinel lymph node biopsy who do not undergo completion axillary dissection, treatment in the prone position may be inappropriate.


Mixture effects of levonorgestrel and ethinylestradiol: estrogenic biomarkers and hormone receptor mRNA expression during sexual programming.
Synthetic progesterone (progestins) and estrogens are widely used pharmaceuticals. Given that their simultaneous unintentional exposure occurs in wildlife and also in human infants, data on mixture effects of combined exposures to these hormones during development is needed. Using the Xenopus (Silurana) tropicalis test system we investigated mixture effects of levonorgestrel (LNG) and ethinylestradiol (EE2) on hormone sensitive endpoints. After larval exposure to LNG (0.1nM), or EE2 (0.1nM) singly, or in combination with LNG (0.01, 0.1, 1.0nM), the gonadal sex ratio was determined histologically and hepatic mRNA levels of genes encoding vitellogenin (vtg beta1) and the estrogen (esr1, esr2), progesterone (ipgr) and androgen (ar) receptors were quantified using quantitative PCR. All EE2-exposed groups showed female-biased sex ratios and increased vtg beta1 mRNA levels compared with the controls. Compared with the EE2-alone group (positive control) there were no significant alterations in vtg beta1 levels or in sex ratios in the co-exposure groups. Exposure to LNG-alone caused an increase in ar mRNA levels in females, but not in males, compared to the controls and the co-exposed groups, indicating that co-exposure to EE2 counteracted the LNG-induced ar levels. No treatment related impacts on the mRNA expression of esr1, esr2, and ipgr in female tadpoles were found, suggesting that these endpoints are insensitive to long-term exposure to estrogen or progestin. Due to the EE2-induced female-biased sex ratios, the mRNA expression data for the low number of males in the EE2-exposed groups were not statistically analyzed. In conclusion, our results suggest that induced vtg expression is a robust biomarker for estrogenic activity in exposure scenarios involving both estrogens and progestins. Developmental exposure to LNG caused an induction of hepatic ar mRNA expression that was antagonized by combined exposure to EE2 and LNG. To our knowledge this is the first study to report effects of combined exposures to EE2 and LNG during the period of sexual programming.


Perceptions of the role of general practice and practical support measures for carers of stroke survivors: a qualitative study.
Informal carers frequently suffer adverse consequences from caring. General practice teams are well positioned to support them. However, what carers of stroke survivors want and expect from general practice, and the practical support measures they might like, remain largely unexplored.The aims of this study are twofold. Firstly it explores both the support stroke carers would like from general practice and their reactions to the community based support proposed in the New Deal. Secondly, perceptions of a general practice team are investigated covering similar topics to carer interviews but from their perspective. Semi-structured interviews were conducted with 13 stroke carers and 10 members of a general practice team. Carers' experiences and expectations of general practice and opinions of support measures from recent government policy were explored. General practice professionals were asked about their perceived role and their perceptions of carers' support needs. Interviews were content analysed. Carers' expectations of support from general practice were low and they neither received nor expected much support for themselves. General practice was seen as reactive primarily because of time constraints. Some carers would appreciate emotional support but others did not want additional services. Responses to recent policy initiatives were mixed with carers saying these might benefit other carers but not themselves.General practice professionals' opinions were broadly similar. They recognise carers' support needs but see their role as reactive, focussed on stroke survivors, rather than carers. Caring was recognised as challenging. Providing emotional support and referral were seen as important but identification of carers was considered difficult. Time constraints limit their support. Responses to recent policy initiatives were positive. Carers' expectations of support from general practice for themselves are low and teams are seen as reactive and time constrained. Both the carers and the general practice team participants emphasised the valuable role of general practice team in supporting stroke survivors. Research is needed to determine general practice teams' awareness and identification of carers and of the difficulties they encounter supporting stroke carers. Carer policy initiatives need greater specificity with greater attention to diversity in carer needs.


Expression and roles of connective tissue growth factor in Meckel's cartilage development.
Meckel's cartilage is a prominent feature of the developing mandible, but its formation and roles remain unclear. Because connective tissue growth factor (CTGF, CCN2) regulates formation of other cartilages, we asked whether it is expressed and what roles it may have in developing mouse Meckel's cartilage. Indeed, CTGF was strongly expressed in anterior, central, and posterior regions of embryonic day (E) 12 condensing Meckel's mesenchyme. Expression decreased in E15 newly differentiated chondrocytes but surged again in E18 hypertrophic chondrocytes located in anterior region and most-rostral half of central region. These cells were part of growth plate-like structures with zones of maturation resembling those in a developing long bone and expressed such characteristic genes as Indian hedgehog (Ihh), collagen X, MMP-9, and vascular endothelial growth factor. At each stage examined perichondrial tissues also expressed CTGF. To analyze CTGF roles, mesenchymal cells isolated from E10 first branchial arches were tested for interaction and responses to recombinant CTGF (rCTGF). The cells readily formed aggregates in suspension culture and interacted with substrate-bound rCTGF, but neither event occurred in the presence of CTGF neutralizing antibodies. In good agreement, rCTGF treatment of micromass cultures stimulated both expression of condensation-associated macromolecules (fibronectin and tenascin-C) and chondrocyte differentiation. Expression of these molecules and CTGF itself was markedly up-regulated by treatment with transforming growth factor-beta1, a chondrogenic factor. In conclusion, CTGF is expressed in highly dynamic manners in developing Meckel's cartilage where it may influence multiple events, including chondrogenic cell differentiation and chondrocyte maturation. CTGF may aid chondrogenesis by acting down-stream of transforming growth factor-beta and stimulating cell-cell interactions and expression of condensation-associated genes.


The caring encounter in nursing.
The concept 'encounter' occurs in caring literature as a synonym for dialogue and relation describing deeper levels of interaction between patient and nurse. In nursing and caring research, the concept 'caring encounter' is often used without further reflection on the meaning of the concept. Encounters are, however, continuously taking place in the world of caring, which calls for a clarification of the concept. This study is an analysis of the concept of caring encounter in nursing from the patients' and nurses' point of view. Rodgers' evolutionary view guided the concept analysis within the theoretical perspective of caritative caring. Peer-reviewed articles in English published between 1990 and 2014 were retrieved from the databases: CINAHL, PubMed, Web of Science, ScienceDirect (Elsevier), Springer Link, Primo Central (Ex Libris) and Academic Search Premier (EBSCO) using different combinations of encounter, caring and nursing as keywords. In all, 28 articles related to caring encounters were included in the analysis after applying inclusion and exclusion criteria. This study was conducted according to good scientific practice. Four antecedents to the caring encounter are found in the nurse's way of being: a reflective way of being; openness, sensitivity, empathy and ability to communicate; confidence, courage and professionalism; and showing respect and supporting dignity. The attributes are as follows: being there, uniqueness and mutuality. As a consequence, the caring encounter influences both patient and nurse. The caring encounter is an encounter between two equal persons where one is nurse and the other is patient. They encounter in mutuality, in true presence, and both have allowed themselves to be the person they are. The results clarify the conceptual differences between relationship and caring communion as the mutuality in the caring encounter differs from the dependence on the other pronounced in the relationship.


Activation and repression of prion protein expression by key regions of intron 1.
Expression of the prion protein is necessary for infection with prion diseases. Altered expression levels may play an important role in susceptibility to infection. Therefore, understanding the mechanisms that regulate prion protein expression is of great importance. It was previously shown that expression of the prion protein is to some degree regulated by an alternative promoter within intron 1. Studies using GFP and luciferase reporter systems were undertaken to determine key sites for the repression and activation of expression of the prion protein driven by intron 1. We identified a region within intron 1 sufficient to drive prion protein expression. Our findings highlight two potential repressor regions. Both regions have binding sites for the known repressor Hes-1. Hes-1 overexpression caused a dramatic decrease in PrP protein expression. Additionally, we have identified Atox-1 as a transcription factor that upregulates prion protein expression. These findings clearly indicate that intron 1 plays a key role in regulation of prion protein expression levels.


Management of phacolytic glaucoma: experience of 135 cases.
We retrospectively analyzed 135 eyes with phacolytic glaucoma. A trabeculectomy was added to standard cataract surgery if symptoms endured for more than seven days, or if preoperative control of intraocular pressure (IOP) with maximal medical treatment was inadequate. In the early postoperative period, IOP was significantly lower in the combined surgery group (89 eyes) compared to the cataract surgery group (46 eyes) (p < 0.001). At 6 months there was no difference in IOP or visual acuity between the two groups. There were no serious complications related to trabeculectomy. It is reasonable to conclude that in eyes with a long duration of phacolytic glaucoma, addition of a trabeculectomy to cataract surgery is safe, prevents postoperative rise in intraocular pressure and decreases the need for systemic hypotensive medications. A randomized trial is on to further address this question.


The impact of an infant's severe congenital heart disease on the family: a prospective cohort study.
The aim of this article is to investigate the impact of a child's severe congenital heart disease on the family and to prospectively examine the influence of disease specific and psychosocial factors on the family. A prospective cohort study. Parents of 104 infants who had undergone cardiopulmonary bypass surgery before the age of 12 months for congenital heart disease were included. None. Parents completed the generic Impact on Family scale and a social support questionnaire; a large number of medical data were extracted from the patients' hospital records. Parents most frequently reported that they were thinking about not having more children and living on a "roller coaster." No difference was found in the total Impact on Family scale score between fathers and mothers. The presence of a genetic disorder in the child and lower levels of perceived social support was significantly associated with a greater impact on the family. The impact of an infant's congenital heart disease on the family is determined both by child's medical condition and family's psychosocial factors. Families with poorer social support network may have the greatest need for professional interventions, especially if their child has an underlying genetic disorder.


The process of exiting vegetarianism: an exploratory study.
The experience, reasons, and contexts associated with leaving vegetarianism were explored. Interviews were conducted with a convenience sample of 19 ex-vegetarians and 15 continuing vegetarians. Exiting vegetarianism is similar to the process of leaving other important individual identities, including exiting diets containing meat. It is a process, not an event, and partially a response to inconvenience, particularly when the person's table companions were not vegetarians. Major life changes and declines in self-perceived health provided occasions to reassess life choices, including the vegetarian commitment. Ex-vegetarians interpreted their vegetarianism as a transition to a new, healthier diet. Including a comparison group of continuing vegetarians revealed that the ex-vegetarians were more likely to have become vegetarians as a result of concern about the well-being of animals and the environment, not animal rights, a value more difficult to compromise. Exiting processes show the five central food values of taste, health, time, cost, and social relationships undermine people's commitment to a diet chosen largely for moral reasons.


Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients?
Postmortem reports highlight the importance of factors that individually or collectively limit survival. The prevalence of pulmonary embolism (PE) at autopsy in lung-transplant recipients has not been characterized previously. We aimed to describe the prevalence of PE, infection, and acute and chronic rejection at autopsy and their respective contributions to death in lung-transplant recipients according to survival posttransplantation. We retrospectively reviewed 126 autopsy reports performed in lung-and heart-lung-transplant recipients between June 1990 and September 2002. PE was identified at autopsy in 34 (27.0%) of 126 lung- and heart-lung-transplant recipients. The prevalence of autopsy-established PE was highest, at 36.4%, in the early group (1-30 days) compared with 20.0% and 23.8% in the intermediate (31-365 days) and late (>365 days) groups, respectively. Although fungal and viral pneumonia were noted most frequently in the early and intermediate groups, bacterial pneumonia was noted in 32% to 45% of autopsies over the posttransplant period. Acute cellular rejection and bronchiolitis obliterans were present in 29.5% and 2.3%, 40.0% and 17.5%, and 35.7% and 42.9% of patients in the early, intermediate, and late groups, respectively. The most frequent cause of death was bacterial infection. The prevalence of PE was highest in mechanically ventilated lung-transplant recipients in the early postoperative period. Heart-lung recipients were at lower risk for PE compared with double- and single-lung recipients. PE may be an under-appreciated complication contributing to respiratory failure in the early postoperative period.


A psycho-linguistic approach for studying adult playfulness: a replication and extension toward relations with humor.
ABSTRACT This study addresses the basic structure of playfulness in adults from a psycho-lexical approach and its relationship with the sense of humor. Using items derived from a corpus analysis of written accounts in the German language, five factors were derived (N = 195); that is, (a) cheerful-engaged; (b) whimsical; (c) creative-loving; (d) intellectual; and (e) impulsive. Their contents strongly overlap in comparison with an earlier study using this approach. However, the correlation of the intellectual component with two current measures of adult playfulness was low, and the impulsive component was not correlated with these measures. The question arises as to whether these aspects exist only as components in the implicit psychological and linguistic theories. The sense of humor was most strongly related with the cheerful-engaged factor while some "humor skills" were particularly related to other factors; for example, finding humor under stress with the intellectual component. This study helps toward a better understanding of the basic structure of playfulness in adults.


Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer.
A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.


More than Just a Brain Disorder: A Five-Point Manifesto for Psychological Care for People with Huntington's Disease.
Huntington's disease (HD) is a rare and complex condition where affected individuals, family members, caregivers, and clinicians face a number of both long-term and fluctuating challenges. The predominant biomedical framework adopted in HD to date has traditionally viewed it as a brain disorder first and foremost. As a consequence, one of the most challenging aspects of the condition-psychological difficulties and their care-is often not given the emphasis it deserves in everyday clinical practice. Here, we propose a manifesto outlining five points to address the quality, effectiveness, availability, and accessibility of psychological care in HD. These include (1) Listening to People with HD, (2) Reformulating Difficulties Psychologically, (3) Exploring New Interventions, (4) Increasing Psychological Provision, and (5) Learning from Other Conditions. As the search for a cure continues, we hope that this manifesto will create a new impetus towards refining the current approach to psychological difficulties in HD and ultimately improve the quality of life of the tens of thousands of families affected by HD worldwide.


Substrain-specific differences in survival and osteonecrosis incidence in a mouse model.
We previously reported strain-specific susceptibility to dexamethasone-induced osteonecrosis in mice. Here we report that BALB/cJ and BALB/cAnNHsd mice display substrain-specific differences in dexamethasone-induced adverse effects. As compared with BALB/cJ mice, BALB/cAnNHsd weighed more (16.6 g compared with 13.7 g) at the beginning of dexamethasone administration on postnatal day 28 and fewer died during the dexamethasone regimen (10% compared with 50%). Although the 2 substrains had similar plasma concentrations of dexamethasone, BALB/cJ mice were more susceptible to developing dexamethasone-induced osteonecrosis. A higher dose of dexamethasone (8 mg/L) throughout the treatment period compared with a lower dose (8 mg/L loading dose during week 1 followed by 4 mg/L for the remainder of the treatment period) and earlier start of treatment (postnatal day 24 compared with postnatal day 28) was required to induce osteonecrosis with a similar frequency in BALB/cAnNHsd mice as in BALB/cJ mice. Our results show, for the first time, substrain-specific differences in the development of osteonecrosis in mice.


Influence of serotinin and norepinephrine on flow capacity/pressure characteristics of feline isolated cerebral arteries.
Isolated feline pial vessel segments (250-400 microns in diameter, 4 mm long) were mounted in Krebs solution in organ baths on L-shaped metal holders connected to pressure transducers. From the distance between the outer limits of the wires (f) and the force recorded by the transducers (F), the transmural pressure and the flow capacity were calculated. Changes in these parameters were produced by increasing the distance between the holders. Norepinephrine (10(-5) M) and serotonin (10(-6) M) were added to the tissue bath at different resting wall tensions. Both norepinephrine and serotonin resulted in contractile responses that were maximal at a resting wall tension of 2 nM/mm. Norepinephrine and serotonin displaced the flow capacity/pressure curve to the right up till at least 112 mm Hg, indicating a displacement of the autoregulatory range to the right.


Community health workers: to train or to restrain? A longitudinal survey to assess the impact of training community health workers in the Bolama Region, Guinea-Bissau.
The shortage in human resources for health affects most dramatically developing countries which frequently use community health workers (CHW) as the basis for health programmes and services. The traditional definition refers CHWs as members of the community who are recruited and trained in health prevention and promotion to provide services within their community. In Guinea-Bissau, CHWs play a fundamental role in the diagnosis and treatment of childhood diarrheal diseases - one of the main health problems in the country. This study is based on 22 CHW, 79% of the total number of CHW in the Sanitary Region of Bolama. The main goal was to assess how training CHW on diarrheal diseases impacted the accuracy of the diagnosis and treatment of these diseases in children under the age of 5 years. Three evaluations were made throughout time - one evaluation before the training and two follow-up evaluations.An observation grid was developed to evaluate the identified signs, symptoms, diagnosis and treatments prescribed by the CHW in consultations to children with a suspicion of diarrhoeal disease. A similar grid was filled by a medical doctor who took the role of the external validation standard.Friedman's variance analysis and Cochran's Q test were performed to compare the accuracy depicted by CHWs in identifying items throughout time. A logistic regression model was also used to check the possible influence of socio-demographic characteristics of CHWs on the accuracy of the diagnosis and treatment prescribed by the CHW. The results show that CHWs improve significantly their performance in identifying the correct diagnosis in the first follow-up moment after the training (P = 0.001, n = 22) but, 3 months later, the effectiveness decreases. No statistical evidence was found for the logistic regression models applied. This progressive loss of performance after training may occur because CHWs fail to apply treatment algorithms and guidelines over time. A limited set of socio-demographic characteristics of the CHWs can influence their performance and should not be disregarded when selecting CHW candidates. The selection, supervision, support and continuous training of CHW are as important as the training provided.


The impact of health transformation plan on hospitalization rates in Iran: An interrupted time series.
The study aims to assess the impact of health transformation plan (HTP) as a major health system reform on hospitalization rate in Iran. Health transformation plan adopted different measures to increase the coverage of basic health insurance, increase the quality of outpatient visit care, improve and expand the family physician program, expand health services to suburban areas, reduce out-of-pocket (OOP) payments for inpatient services, and update tariffs to more realistic ones. We selected Kurdistan province, a province that was not a patient referral hub, for the collection of monthly hospitalization data over a period of 50 months. Interrupted time series (ITS) analysis was carried out, and segmented regression analysis was employed to assess the abrupt (or short-term) and gradual (or long-term) effects of HTP on hospitalization rate. Although before the intervention, there was no significant increase or decline in hospitalization rate in the Kurdistan province, after the implementation of HTP, a significant increase in the intercept and slope of hospitalization rate was observed (P < 0.001). Health transformation plan has improved the utilization of hospitalization care services in a province that historically had been suffering from underutilized hospital services.


Multi-Observation Blind Deconvolution with an Adaptive Sparse Prior.
This paper describes a robust algorithm for estimating a single latent sharp image given multiple blurry and/or noisy observations. The underlying multi-image blind deconvolution problem is solved by linking all of the observations together via a Bayesian-inspired penalty function, which couples the unknown latent image along with a separate blur kernel and noise variance associated with each observation, all of which are estimated jointly from the data. This coupled penalty function enjoys a number of desirable properties, including a mechanism whereby the relative-concavity or sparsity is adapted as a function of the intrinsic quality of each corrupted observation. In this way, higher quality observations may automatically contribute more to the final estimate than heavily degraded ones, while troublesome local minima can largely be avoided. The resulting algorithm, which requires no essential tuning parameters, can recover a sharp image from a set of observations containing potentially both blurry and noisy examples, without knowing a priori the degradation type of each observation. Experimental results on both synthetic and real-world test images clearly demonstrate the efficacy of the proposed method.


Widely available active sites on Ni2P for electrochemical hydrogen evolution--insights from first principles calculations.
We present insights into the mechanism and the active site for hydrogen evolution on nickel phosphide (Ni2P). Ni2P was recently discovered to be a very active non-precious hydrogen evolution catalyst. Current literature attributes the activity of Ni2P to a particular site on the (0001) facet. In the present study, using Density Functional Theory (DFT) calculations, we show that several widely available low index crystal facets on Ni2P have better properties for a high catalytic activity. DFT calculations were used to identify moderately bonding nickel bridge sites and nickel hollow sites for hydrogen adsorption and to calculate barriers for the Tafel pathway. The investigated surfaces in this study were the (101̅0), (1̅1̅20), (112̅0), (112̅1) and (0001) facets of the hexagonal Ni2P crystal. In addition to the DFT results, we present experiments on Ni2P nanowires growing along the 〈0001〉 direction, which are shown as efficient hydrogen evolution catalysts. The experimental results add these nanowires to a variety of different morphologies of Ni2P, which are all active for HER.


Organocatalysis with dendrimers.
This review gives an overview of the use of dendrimers and dendrons as organocatalysts, i.e. as catalysts in the absence of any metal. A large variety of dendrimeric structures have already been used for such a purpose, varying in size (generation), type and location (core or surface) of the organocatalytic entities, and overall chemical composition. The main types of reactions catalyzed concern bond formation (in particular C-C bonds), bond cleavage (in particular of esters), reductions and oxidations. In many cases, good to excellent enantioselectivities have been observed, in some cases associated with a positive dendritic effect (better properties when the generation of the dendrimer increases). Due to their large size compared to products, the dendrimeric organocatalysts can be often recovered and reused several times.


Interaction between smoking and polymorphism in the promoter region of the VEGFA gene is associated with ischemic heart disease and myocardial infarction in rheumatoid arthritis.
To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction. PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA-2578A/C (rs699947), -460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses. Strong linkage disequilibrium was detected among VEGFA-2578, -460, and +405. SNP located in the VEGFA promoter region (-2578, -460) were found to be associated with IHD and MI, whereas +405 and +936, in the 5'-untranslated region (UTR) and 3'-UTR, respectively, were not. Haplotype analysis suggested that the A/C/G haplotype was associated with increased risk of IHD (OR 2.37, 95% CI 1.22-4.62) and MI (OR 4.10, 95% CI 1.45-11.49). Smoking was also independently associated with IHD and MI, and evidence of interaction between smoking and the VEGFA promoter SNP was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the VEGFA-2578 A allele and smoking (OR 3.52 and 7.11, respectively), independent of risk factors such as age, sex, diabetes, C-reactive protein, hypercholesterolemia, and hypertension. Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in patients with RA.


Assessment of Hypertension Using Clinical Electrocardiogram Features: A First-Ever Review.
Hypertension affects an estimated 1.4 billion people and is a major cause of morbidity and mortality worldwide. Early diagnosis and intervention can potentially decrease cardiovascular events later in life. However, blood pressure (BP) measurements take time and require training for health care professionals. The measurements are also inconvenient for patients to access, numerous daily variables affect BP values, and only a few BP readings can be collected per session. This leads to an unmet need for an accurate, 24-h continuous, and portable BP measurement system. Electrocardiograms (ECGs) have been considered as an alternative way to measure BP and may meet this need. This review summarizes the literature published from January 1, 2010, to January 1, 2020, on the use of only ECG wave morphology to monitor BP or identify hypertension. From 35 articles analyzed (9 of those with no listed comorbidities and confounders), the P wave, QTc intervals and TpTe intervals may be promising for this purpose. Unfortunately, with the limited number of articles and the variety of participant populations, we are unable to make conclusions about the effectiveness of ECG-only BP monitoring. We provide 13 recommendations for future ECG-only BP monitoring studies and highlight the limited findings in pregnant and pediatric populations. With the advent of convenient and portable ECG signal recording in smart devices and wearables such as watches, understanding how to apply ECG-only findings to identify hypertension early is crucial to improving health outcomes worldwide.


Using macrophage activation to augment immunotherapy of established tumours.
Successful immunotherapy will require alteration of the tumour microenvironment and/or decreased immune suppression. Tumour-associated macrophages (TAMs) are one major factor affecting tumour microenvironment. We hypothesised that altering TAM phenotype would augment the efficacy of immunotherapy. We and others have reported that 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA, Vadimezan) has the ability to change TAM phenotypes, inducing a tumour microenvironment conducive to antitumour immune responses. We therefore combined DMXAA with active immunotherapies, and evaluated anti-tumour efficacy, immune cell phenotypes (flow cytometry), and tumour microenvironment (RT-PCR). In several different murine models of immunotherapy for lung cancer, DMXAA-induced macrophage activation significantly augmented the therapeutic effects of immunotherapy. By increasing influx of neutrophils and anti-tumour (M1) macrophages to the tumour, DMXAA altered myeloid cell phenotypes, thus changing the intratumoural M2/non-M2 TAM immunoinhibitory ratio. It also altered the tumour microenvironment to be more pro-inflammatory. Modulating macrophages during immunotherapy resulted in increased numbers, activity, and antigen-specificity of intratumoural CD8(+) T cells. Macrophage depletion reduced the effect of combining immunotherapy with macrophage activation, supporting the importance of TAMs in the combined effect. Modulating intratumoural macrophages dramatically augmented the effect of immunotherapy. Our observations suggest that addition of agents that activate TAMs to immunotherapy should be considered in future trials.


Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.
Etk (also called Bmx) is a member of the Btk tyrosine kinase family and is expressed in a variety of hematopoietic, epithelial, and endothelial cells. We have explored biological functions, regulators, and effectors of Etk. Coexpression of v-Src and Etk led to a transphosphorylation on tyrosine 566 of Etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of Etk. STAT3, which was previously shown to be activated by Etk, associated with Etk in vivo. To investigate whether Etk could mediate v-Src-induced activation of STAT3 and cell transformation, we overexpressed a dominant-negative mutant of Etk in an immortalized, untransformed rat liver epithelial cell line, WB, which contains endogenous Etk. Dominant-negative inactivation of Etk not only blocked v-Src-induced tyrosine phosphorylation and activation of STAT3 but also caused a great reduction in the transforming activity of v-Src. In NIH3T3 cells, although Etk did not itself induce transformation, it effectively enhanced the transforming ability of a partially active c-Src mutant (c-Src378G). Furthermore, Etk activated STAT3-mediated gene expression in synergy with this Src mutant. Our findings thus indicate that Etk is a critical mediator of Src-induced cell transformation and STAT3 activation. The role of STAT3 in Etk-mediated transformation was also examined. Expression of Etk in a human hepatoma cell line Hep3B resulted in a significant increase in its transforming ability, and this effect was abrogated by dominant-negative inhibition of STAT3. These data strongly suggest that Etk links Src to STAT3 activation. Furthermore, Src-Etk-STAT3 is an important pathway in cellular transformation.


Flow diversion for intracranial aneurysms: a review.
The introduction of flow diverters for treatment of intracranial aneurysms represents a major paradigm shift in the treatment of these lesions. The theoretical hallmark of flow diverters is the treatment of the diseased segment harboring the aneurysm instead of treating the aneurysm itself. Flow diverters are designed to induce disruption of flow near the aneurysm neck while preserving flow into parent vessel and adjacent branches. After flow diversion, intra-aneurysmal thrombosis occurs, followed by shrinkage of the aneurysmal sac as the thrombus organizes and retracts. Preliminary clinical series document effective treatment of wide-neck and/or large and giant aneurysms with acceptable complication rates. However, several questions remain unanswered related to the incidence and mechanisms of aneurysm rupture after treatment with flow diverters, fate of small perforating vessels, and long-term patency rates.


Postural changes of plasma renin activity after renal transplantation.
1. Postural changes of plasma renin activity (PRA) before and after the administration of a beta-blocking agent (oxprenolol) were studied in nine patients with renal homotransplantation and in ten normal subjects. 2. In normal subjects PRA always increased during upright posture without any correlation with postural changes in mean arterial pressure. Oxprenolol reduced the postural increase of PRA. 3. A postural increase of PRA could be detected as early as 20--25 days after renal transplantation, and appeared with increasing frequency as time elapsed. 4. There was a significant inverse correlation (r = -0.794, P less than 0.001) between the postural changes of PRA and those of mean arterial pressure. 5. These results suggest that in patients with renal homotransplantation the postural increase of PRA can only partly be due to circulating catecholamines or the sympathetic nervous system and may be explained by inverse changes in the mean arterial pressure.


Analysis of genome plasticity in pathogenic and commensal Escherichia coli isolates by use of DNA arrays.
Genomes of prokaryotes differ significantly in size and DNA composition. Escherichia coli is considered a model organism to analyze the processes involved in bacterial genome evolution, as the species comprises numerous pathogenic and commensal variants. Pathogenic and nonpathogenic E. coli strains differ in the presence and absence of additional DNA elements contributing to specific virulence traits and also in the presence and absence of additional genetic information. To analyze the genetic diversity of pathogenic and commensal E. coli isolates, a whole-genome approach was applied. Using DNA arrays, the presence of all translatable open reading frames (ORFs) of nonpathogenic E. coli K-12 strain MG1655 was investigated in 26 E. coli isolates, including various extraintestinal and intestinal pathogenic E. coli isolates, 3 pathogenicity island deletion mutants, and commensal and laboratory strains. Additionally, the presence of virulence-associated genes of E. coli was determined using a DNA "pathoarray" developed in our laboratory. The frequency and distributional pattern of genomic variations vary widely in different E. coli strains. Up to 10% of the E. coli K-12-specific ORFs were not detectable in the genomes of the different strains. DNA sequences described for extraintestinal or intestinal pathogenic E. coli are more frequently detectable in isolates of the same origin than in other pathotypes. Several genes coding for virulence or fitness factors are also present in commensal E. coli isolates. Based on these results, the conserved E. coli core genome is estimated to consist of at least 3,100 translatable ORFs. The absence of K-12-specific ORFs was detectable in all chromosomal regions. These data demonstrate the great genome heterogeneity and genetic diversity among E. coli strains and underline the fact that both the acquisition and deletion of DNA elements are important processes involved in the evolution of prokaryotes.


Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group.
Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown. To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association. Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment. Outpatient diabetes clinics in 15 UK hospitals. A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m2. After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin. Fasting plasma glucose and HbA1c levels, and the proportion of patients who achieved target levels below 7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis. The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA1c levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients. Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA1c below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.


Pathology of patients with Chagas' disease and acquired immunodeficiency syndrome.
The main pathologic findings in 23 patients with acquired immunodeficiency syndrome (AIDS) and Chagas' disease are reviewed; five are from our own experience and 18 from the literature. The presence of Trypanosoma cruzi parasites and/or T. cruzi antibodies in blood and cerebrospinal fluid was recorded and computerized tomograms of the brain were evaluated. Twenty (87%) of the 23 subjects developed severe, multifocal or diffuse meningoencephalitis with necrosis and hemorrhage associated with numerous tissue parasites. The second most severely affected site was the heart. Seven (30.4%) of the 23 cases had myocarditis on pathologic examination. It was acute in four patients, chronic in two, and simultaneously acute and chronic in one. Acute myocarditis and meningoencephalitis are interpreted as being caused by relapses of chronic T. cruzi infections. An AIDS permissive role is suggested for these conditions since immunologic defense against T. cruzi is mediated mainly by T lymphocytes, whose CD4 subpopulation is depleted in patients with this disease. Consequently, AIDS is a factor that may favor the reactivation of T. cruzi infections. The lesions reported in the association of Chagas' disease with AIDS were compared with those reported from patients without AIDS having fatal, acute, vector-transmitted infections, contaminated blood transfusions, or accidental exposures in the laboratory. For the latter three, meningoencephalitis is uncommon. Only immunosuppressed cases of Chagas' disease have been described as having a pseudotumoral presentation that shows expanding lesions with a mass effect in the cranial cavity that causes intracranial hypertension and simulates neoplasms (tumors such as gliomas, lymphomas, metastases, etc.).


What passes and fails as health policy and management.
The field of health policy and management (HPAM) faces a gap between theory, policy, and practice. Despite decades of efforts at reforming health policy and health care systems, prominent analysts state that the health system is "stuck" and that models for change remain "aspirational." We discuss four reasons for the failure of current ideas and models for redesigning health care: (1) the dominance of microeconomic thinking; (2) the lack of comparative studies of health care organizations and the limits of health management theory in recognizing the importance of local contexts; (3) the separation of HPAM from the rank and file of health care, particularly physicians; and (4) the failure to expose medical students to issues of HPAM. We conclude with suggestions for rethinking how the field of HPAM might generate more-promising policies for health care providers and managers by abandoning the illusion of context-free theories and, instead, seeking to facilitate the processes by which organizations can learn to improve their own performance.


A three-in-one-bullet for oesophageal cancer: replication fork collapse, spindle attachment failure and enhanced radiosensitivity generated by a ruthenium(ii) metallo-intercalator.
Substitutionally inert ruthenium(ii) polypyridyl complexes have been developed as DNA intercalating agents yet cellular DNA damage responses to this binding modality are largely unexplored. Here, we show the nuclear-targeting complex [Ru(phen)2(tpphz)]2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) generates rapid and pronounced stalling of replication fork progression in p53-deficient human oesophageal cancer cells. In response, replication stress and double-strand break (DSB) DNA damage response (DDR) pathways are activated and cell proliferation is inhibited by growth arrest. Moreover, mitotic progression is compromised by [Ru(phen)2(tpphz)]2+, where the generation of metaphase chromosome spindle attachment failure results in spindle assembly checkpoint (SAC) activation. This dual mechanism of action results in preferential growth inhibition of rapidly-proliferating oesophageal cancer cells with elevated mitotic indices. In addition to these single-agent effects, [Ru(phen)2(tpphz)]2+ functions as a radiosensitizer with efficiency comparable to cisplatin, which occurs through a synergistic enhancement of DNA damage. These results establish that DNA replication is the target for [Ru(phen)2(tpphz)]2+ and provide the first experimental evidence that ruthenium-based intercalation targets multiple genome integrity pathways in cancer cells, thereby achieving enhanced selectivity compared to existing DNA-damaging agents such as cisplatin.


Trade-offs between growth and reproduction in female bison.
The extent to which (a) larger females produce more or larger offspring, (b) reproduction imposes costs, and (c) the benefits of early reproduction outweigh the costs was examined for female bison (Bison bison) with data from an 8-year period. Description of ontogenetic patterns indicated that reproductive performance reached a plateau near the end of the growth period; changes with age in fecundity were little related to those of body weight during the typical reproductive lifespan (age 3-18 years). Examination of inter-and intra-individual variation showed that the relationship between growth and reproduction depends on the age of subjects. Larger juveniles matured earlier and were more fecund (though smaller) as adults. In contrast, post-pubertal growth was negatively related to reporductive performance, although intra-individual weight variation was positively associated with pregnancy rate. Fecundity was not generally lower in years after reproduction than after barren years, in spite of weight loss, suggesting that reproduction did not impose significant fitness costs. On the other hand, offspring quality was lower when mothers reproduced in successive rather than alternate years. Early maturation resulted in immediate costs, including reduced growth and infertility in the year after first parturition. However, there were long-term benefits: fecundity in the first 7-9 years was highest for early-maturing and lowest for late-maturing females, suggesting that reproductive success is greater for early-maturing females despite reduced growth. In the present study, trade-offs between growth and reproduction did not appear to reflect substantial costs as measured by long-term reproductive success.


Coded strobing photography: compressive sensing of high speed periodic videos.
We show that, via temporal modulation, one can observe and capture a high-speed periodic video well beyond the abilities of a low-frame-rate camera. By strobing the exposure with unique sequences within the integration time of each frame, we take coded projections of dynamic events. From a sequence of such frames, we reconstruct a high-speed video of the high-frequency periodic process. Strobing is used in entertainment, medical imaging, and industrial inspection to generate lower beat frequencies. But this is limited to scenes with a detectable single dominant frequency and requires high-intensity lighting. In this paper, we address the problem of sub-Nyquist sampling of periodic signals and show designs to capture and reconstruct such signals. The key result is that for such signals, the Nyquist rate constraint can be imposed on the strobe rate rather than the sensor rate. The technique is based on intentional aliasing of the frequency components of the periodic signal while the reconstruction algorithm exploits recent advances in sparse representations and compressive sensing. We exploit the sparsity of periodic signals in the Fourier domain to develop reconstruction algorithms that are inspired by compressive sensing.


Importance of the type of provider seen to begin health care for a new episode low back pain: associations with future utilization and costs.
Low back pain (LBP) care can involve many providers. The provider chosen for entry into care may predict future health care utilization and costs. The objective of this study was to explore associations between entry settings and future LBP-related utilization and costs. A retrospective review of claims data identified new entries into health care for LBP. We examined the year after entry to identify utilization outcomes (imaging, surgeon or emergency visits, injections, surgery) and total LBP-related costs. Multivariate models with inverse probability weighting on propensity scores were used to evaluate relationships between utilization and cost outcomes with entry setting. 747 patients were identified (mean age = 38.2 (± 10.7) years, 61.2% female). Entry setting was primary care (n = 409, 54.8%), chiropractic (n = 207, 27.7%), physiatry (n = 83, 11.1%) and physical therapy (n = 48, 6.4%). Relative to primary care, entry in physiatry increased risk for radiographs (OR = 3.46, P = 0.001), advanced imaging (OR = 3.38, P < 0.001), injections (OR = 4.91, P < 0.001), surgery (OR = 4.76, P = 0.012) and LBP-related costs (standardized Β = 0.67, P < 0.001). Entry in chiropractic was associated with decreased risk for advanced imaging (OR = 0.21, P = 0.001) or a surgeon visit (OR = 0.13, P = 0.005) and increased episode of care duration (standardized Β = 0.51, P < 0.001). Entry in physical therapy decreased risk of radiographs (OR = 0.39, P = 0.017) and no patient entering in physical therapy had surgery. Entry setting for LBP was associated with future health care utilization and costs. Consideration of where patients chose to enter care may be a strategy to improve outcomes and reduce costs.


Optoacoustic imaging of the skin.
Optoacoustic (OA, photoacoustic) imaging capitalizes on the synergistic combination of light excitation and ultrasound detection to empower biological and clinical investigations with rich optical contrast while effectively bridging the gap between micro and macroscopic imaging realms. State-of-the-art OA embodiments consistently provide images at micron-scale resolution through superficial tissue layers by means of focused illumination that can be smoothly exchanged for acoustic-resolution images at diffuse light depths of several millimetres to centimetres via ultrasound beamforming or tomographic reconstruction. Taken together, this unique multi-scale imaging capacity opens unprecedented capabilities for high-resolution in vivo interrogations of the skin at scalable depths. Moreover, diverse anatomical and functional information is retrieved via dynamic mapping of endogenous chromophores such as haemoglobin, melanin, lipids, collagen, water and others. This, along with the use of non-ionizing radiation, facilitates a clinical translation of the OA modalities. We review recent progress in OA imaging of the skin in preclinical and clinical studies exploiting the rich contrast provided by endogenous substances in tissues. The imaging capabilities of existing approaches are discussed in the context of initial translational studies on skin cancer, inflammatory skin diseases, wounds and other conditions.


Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development.
Loss of photoreceptor function is responsible for a variety of blinding diseases, including retinitis pigmentosa. Advances in microtechnology have led to the development of electronic visual prostheses which are currently under investigation for the treatment of human blindness. The design of a subretinal prosthesis requires that the stimulation device should be implantable in the subretinal space of the eye. Current limitations in eye surgery have to be overcome to demonstrate the feasibility of this approach and to determine basic stimulation parameters. Therefore, polyimide film-bound electrodes were implanted in the subretinal space in anaesthetized domestic pigs as a prelude to electrical stimulation in acute experiments. Eight eyes underwent surgery to demonstrate the transscleral implantability of the device. Four of the eight eyes were stimulated electrically. In these four animals the cranium was prepared for epidural recording of evoked visual cortex responses, and stimulation was performed with sequences of current impulses. All eight subretinal implantation procedures were carried out successfully with polyimide film electrodes and each electrode was implanted beneath the outer retina of the posterior pole of the operated eyes. Four eyes were used for neurophysiological testing, involving recordings of epidural cortical responses to light and electrical stimulation. A light stimulus response, which occurred 40 ms after stimulation, proved the integrity of the operated eye. The electrical stimuli occurred about 20 ms after the onset of stimulation. The stimulation threshold was approximately 100 microA. Both the threshold and the cortical responses depended on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. The subretinal implantation of complex stimulation devices using the transscleral procedure with consecutive subretinal stimulation is feasible in acute experiments in an animal model approximating to the situation in humans. The domestic pig is an appropriate animal model for basic testing of subretinal implants. Animal experiments with chronically implanted devices and long-term stimulation are advisable to prepare the field for successful human experiments.


Botulinum neurotoxin for pain management: insights from animal models.
The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models.


Can healthcare boards really make a difference in quality and safety?
There is now a heightened interest on the part of many Canadian healthcare boards in improving processes for assuring quality and safety. This interest has been driven by a number of reports and studies which have identified significant quality and safety issues and the need for greater attention to these by those who lead, including governing boards. Despite progress by some boards, there are those who continue to struggle with their role and how it should be fulfilled. This article addresses why, above all else, quality and safety require greater board attention, precisely what boards should do to fulfill their role and how they should organize themselves to achieve it. Special emphasis is placed on how the boards' role in quality and safety, if properly fulfilled, can and will have a beneficial impact on outcomes.


The experience of spirituality from the perspective of people living with dementia: A systematic review and meta-synthesis.
Spirituality is an important aspect of humanity. Concerned with deriving meaning from events, and connection with others, it provides a mechanism for some to cope with illness and disability. While spiritual support is recognised as important, little is known about the spiritual needs of those people experiencing dementia. This meta-synthesis considers the experiences of spirituality from the perspective of people living with a diagnosis of dementia. Using a review protocol, key words from a preliminary scoping review were used to direct database searches in November 2013. A total of 667 papers were initially identified. However, following careful quality review assessment a final eight papers were selected. Findings demonstrated the ongoing importance of spirituality to people living with dementia and its importance as a means of finding hope, meaning and linkage with past, present and future. Expression of spirituality through faith practices, contact with faith communities, and the impact of dementia on these, were also highlighted.


Engineering a selectable marker for hyperthermophiles.
Limited thermostability of antibiotic resistance markers has restricted genetic research in the field of extremely thermophilic Archaea and bacteria. In this study, we used directed evolution and selection in the thermophilic bacterium Thermus thermophilus HB27 to find thermostable variants of a bleomycin-binding protein from the mesophilic bacterium Streptoalloteichus hindustanus. In a single selection round, we identified eight clones bearing five types of double mutated genes that provided T. thermophilus transformants with bleomycin resistance at 77 degrees C, while the wild-type gene could only do so up to 65 degrees C. Only six different amino acid positions were altered, three of which were glycine residues. All variant proteins were produced in Escherichia coli and analyzed biochemically for thermal stability and functionality at high temperature. A synthetic mutant resistance gene with low GC content was designed that combined four substitutions. The encoded protein showed up to 17 degrees C increased thermostability and unfolded at 85 degrees C in the absence of bleomycin, whereas in its presence the protein unfolded at 100 degrees C. Despite these highly thermophilic properties, this mutant was still able to function normally at mesophilic temperatures in vivo. The mutant protein was co-crystallized with bleomycin, and the structure of the binary complex was determined to a resolution of 1.5 A. Detailed structural analysis revealed possible molecular mechanisms of thermostabilization and enhanced antibiotic binding, which included the introduction of an intersubunit hydrogen bond network, improved hydrophobic packing of surface indentations, reduction of loop flexibility, and alpha-helix stabilization. The potential applicability of the thermostable selection marker is discussed.


IoTNet: An Efficient and Accurate Convolutional Neural Network for IoT Devices.
Two main approaches exist when deploying a Convolutional Neural Network (CNN) on resource-constrained IoT devices: either scale a large model down or use a small model designed specifically for resource-constrained environments. Small architectures typically trade accuracy for computational cost by performing convolutions as depth-wise convolutions rather than standard convolutions like in large networks. Large models focus primarily on state-of-the-art performance and often struggle to scale down sufficiently. We propose a new model, namely IoTNet, designed for resource-constrained environments which achieves state-of-the-art performance within the domain of small efficient models. IoTNet trades accuracy with computational cost differently from existing methods by factorizing standard 3 × 3 convolutions into pairs of 1 × 3 and 3 × 1 standard convolutions, rather than performing depth-wise convolutions. We benchmark IoTNet against state-of-the-art efficiency-focused models and scaled-down large architectures on data sets which best match the complexity of problems faced in resource-constrained environments. We compare model accuracy and the number of floating-point operations (FLOPs) performed as a measure of efficiency. We report state-of-the-art accuracy improvement over MobileNetV2 on CIFAR-10 of 13.43% with 39% fewer FLOPs, over ShuffleNet on Street View House Numbers (SVHN) of 6.49% with 31.8% fewer FLOPs and over MobileNet on German Traffic Sign Recognition Benchmark (GTSRB) of 5% with 0.38% fewer FLOPs.


Evaluating health visitor assessments of mother-infant interactions: a mixed methods study.
Given the significance of reliably detecting cases where mother-infant relationships are not developing successfully, it is important that initial assessment processes are as sensitive and specific as possible. This study sought to examine the processes by which health visitors identify problems in mother-infant relationships in the post-natal period. Mixed methods. Two universities and two primary care trusts. In Phase One 17 first-time mothers and their 6- to 16-week-old infants were recruited. In Phase Two, a sample of 12 health visitors participated. The study incorporated two data collection phases. In Phase One, each mother's interaction with her baby was video-recorded for 20min in an observation laboratory. The video-recordings were coded and resultant data were analysed to derive a number of quantitative measures of interaction quality, including mothers' responsiveness and sensitivity to their infants as rated by the Global Ratings Scales (GRS) of Mother-Infant Interaction. In Phase Two, 12 health visitors rated and assessed 9 clips of the video-recorded mother-infant interactions. The rationales for their ratings were then explored through in-depth interviews. Health visitor ratings of the video clips were compared to the GRS ratings. The relationship between the main focus of each health visitor rating, as reported in the interview, and the consistency of ratings with the GRS ratings were then investigated. Correlations between individual health visitors' ratings and the GRS ratings ranged from .17 to .83 and were statistically significant in only four cases. There was a weak relationship with health visitors' years of experience (r(s)=.47, NS). When explaining their judgements, health visitors tended to comment on the mother's behaviours or the relationship between the mother and baby and often ignored the behaviour of the baby. There was a highly significant relationship between the consistency of health visitor/GRS ratings and the number of references to the baby in the health visitors' explanations (r(s)=.75, p=.005). This study contributes to the understanding of how health visitors make assessments of mother-infant interactions. The frequent lack of attention and reference to the baby's behaviour suggests an area for further training.


Euryarchaeal genomes are folded into SMC-dependent loops and domains, but lack transcription-mediated compartmentalization.
Hi-C has become a routine method for probing the 3D organization of genomes. However, when applied to prokaryotes and archaea, the current protocols are expensive and limited in their resolution. We develop a cost-effective Hi-C protocol to explore chromosome conformations of these two kingdoms at the gene or operon level. We first validate it on E. coli and V. cholera, generating sub-kilobase-resolution contact maps, and then apply it to the euryarchaeota H. volcanii, Hbt. salinarum, and T. kodakaraensis. With a resolution of up to 1 kb, we explore the diversity of chromosome folding in this phylum. In contrast to crenarchaeota, these euryarchaeota lack (active/inactive) compartment-like structures. Instead, their genomes are composed of self-interacting domains and chromatin loops. In H. volcanii, these structures are regulated by transcription and the archaeal structural maintenance of chromosomes (SMC) protein, further supporting the ubiquitous role of these processes in shaping the higher-order organization of genomes.


New light-sensitive cofactor required for oxidation of succinate by Mycobacterium phlei.
Irradiation of the electron transport particles of Mycobacterium phlei with light at a wavelength of 360 manometers resulted in a loss of oxidase activities of succinate and the reduced form of nicotinamide adenine dinucleotide. The lesion in the two pathways caused by irradiation of the particles differs. The succinoxidase pathway was more labile to irradiation than the pathway linked to nicotinamide adenine dinucleotide. Restoration of succinoxidase activity (up to 50 to 60 percent) occurred on addition of a thermostable, water-soluble material obtained from Mycobacterium phlei cells or with an extract of mitochondria from boiled rat liver. Other known cofactors, such as flavine adenine dinucleotide, flavine mononucleotide, benzo- and naphthoquinones, as well as sulfhydryl agents, failed to restore succinoxidase activity after irradiation. Water-soluble material from Mycobacterium phlei appears to function between the flavoprotein and cytochrome b on the succinoxidase pathway. In contrast to the requirements for restoration of the pathway linked to nicotinamide adenine dinucleotide, restoration of succinoxidase does not occur with quinones or other cofactors such as flavine adenine dinucleotide.


Giant distal superior cerebellar artery aneurysm: case report and review of the literature.
Aneurysms arising from the distal portion of superior cerebellar artery are infrequently seen. They are usually assumed to result from local arterial wall disruption like proximal supratentorial artery aneurysms. Depending on institutional facilities, these particular aneurysms can be treated either by a microsurgical procedure or interventional radiological technique. In general, surgical clipping has been recommended for these lesions. In this report we describe a 44-year old man who presented with a subarachnoid hemorrhage in the right cerebellopontine angle and was diagnosed with a giant aneurysm arising from the cisternal portion of the right superior cerebellar artery. The patient underwent surgery; microsurgical clipping of the aneurysm through subtemporal craniotomy was performed with no difficulty. We conclude that surgical therapy is suitable for the majority of aneurysms arising from the distal portion of the superior cerebellar artery.


Single-image super-resolution using sparse regression and natural image prior.
This paper proposes a framework for single-image super-resolution. The underlying idea is to learn a map from input low-resolution images to target high-resolution images based on example pairs of input and output images. Kernel ridge regression (KRR) is adopted for this purpose. To reduce the time complexity of training and testing for KRR, a sparse solution is found by combining the ideas of kernel matching pursuit and gradient descent. As a regularized solution, KRR leads to a better generalization than simply storing the examples as has been done in existing example-based algorithms and results in much less noisy images. However, this may introduce blurring and ringing artifacts around major edges as sharp changes are penalized severely. A prior model of a generic image class which takes into account the discontinuity property of images is adopted to resolve this problem. Comparison with existing algorithms shows the effectiveness of the proposed method.


Metabolism of the leukotriene receptor antagonist 5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid (SK&F 102922) in the guinea pig. Rearrangement of the acyl glucuronide.
A primary route of inactivation of leukotrienes and their receptor antagonists (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega oxidation. Therefore, these experiments were designed to characterize the metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5 mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five metabolites and parent (18% of administered dose) were present in bile. One metabolite (M1), which accounted for less than 10% of the excreted radioactivity, was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together accounted for greater than 50% of excreted radioactivity, had mass spectra consistent with acyl glucuronides. All three metabolites were alkali labile, whereas only one metabolite (M2) was susceptible to beta-glucuronidase hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2 that were formed by a nonenzymic reaction involving migration of the aglycone (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta-glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half-lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can account for much of the metabolic fate of SK&F 102922 and, potentially, other structurally related LTRAs or endogenous leukotrienes themselves.


How to Fully Represent Expert Information about Imprecise Properties in a Computer System - Random Sets, Fuzzy Sets, and Beyond: An Overview.
To help computers make better decisions, it is desirable to describe all our knowledge in computer-understandable terms. This is easy for knowledge described in terms on numerical values: we simply store the corresponding numbers in the computer. This is also easy for knowledge about precise (well-defined) properties which are either true or false for each object: we simply store the corresponding "true" and "false" values in the computer. The challenge is how to store information about imprecise properties. In this paper, we overview different ways to fully store the expert information about imprecise properties. We show that in the simplest case, when the only source of imprecision is disagreement between different experts, a natural way to store all the expert information is to use random sets; we also show how fuzzy sets naturally appear in such random-set representation. We then show how the random-set representation can be extended to the general ("fuzzy") case when, in addition to disagreements, experts are also unsure whether some objects satisfy certain properties or not.


Decline in 20-year mortality after myocardial infarction in patients with chronic kidney disease: evolution from the prethrombolysis to the percutaneous coronary intervention era.
Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Here we measured temporal trends in treatment and mortality after myocardial infarction (MI) depending on kidney function at presentation in 12,087 patients admitted for MI to a coronary care unit from 1985 to 2008. The patients were categorized into those with normal kidney function (estimated glomerular filtration rate over 90 ml/min per 1.73 m(2)), and those with CKD as defined by Kidney Foundation practice guidelines, with 8632 patients (71%) at CKD stages 2-5. Use of evidence-based care increased over time in all CKD stages. Mortality rates fell over the entire time period. When comparing data from 2000-2008 to that from 1985-1990, adjusted 30-day mortality fell both in patients with CKD stages 4-5 (adjusted odds 0.33, 95% confidence interval 0.18-0.60) and in those without kidney impairment (adjusted odds 0.21, 95% confidence interval 0.10-0.42). This mortality decrease was sustained during long-term follow-up. There was no significant interaction between kidney function and decade of admission. Overall, median survival was over 20, 15, 8, and 1.8 years for patients with normal kidney function, stage 2, stage 3, and stage 4-5 CKD, respectively. Thus, during the past 25 years, treatment of patients with a MI improved substantially with a concomitant decline in mortality. Although our findings were similar for all stages of kidney function, the prognosis remains poor for patients with stage 4-5 CKD.


The Dysregulation Profile in middle childhood and adolescence across reporters: factor structure, measurement invariance, and links with self-harm and suicidal ideation.
Recently, a phenotype of severe dysregulation, the Dysregulation Profile (DP), has been identified. DP consists of elevated scores on the Anxious/Depressed (AD), Aggressive Behavior (AGG) and Attention Problems (AP) scales of the Child Behavior Checklist (CBCL), Teacher Report Form (TRF), or Youth Self Report (YSR). A drawback in current research is that DP has been conceptualized and operationalized in different manners and research on the factor structure of DP is lacking. Therefore, we examined the factor structure of DP across multiple reporters, measurement invariance across gender, parents, and time, as well as links between DP and self-harm and suicidal ideation. Data from a large community sample were used (N = 697), covering middle childhood (Mage = 7.90, (SD = 1.16) and adolescence (Mage = 13.93, SD = 1.14). Mothers, fathers, teachers, and youth themselves reported on children's emotional and behavioral problems using the CBCL, TRF, and YSR. Results indicated that in middle childhood and in adolescence, a bifactor model with a general factor of Dysregulation alongside three specific factors of AD, AGG, and AP fitted best, compared to a second-order or one-factor model. The model showed good fit for mother, father, teacher, and youth reports and showed invariance across gender, parents and time. Youth, mother, and father reported Dysregulation was uniquely and positively related to adolescent-reported self-harm and suicidal ideation. The DP is best conceptualized as a broad dysregulation syndrome, which exists over and above anxiety/depression, aggression, and attention problems as specific problems. The bifactor model of DP explains the uniqueness and interrelatedness of these behavioral problems and can help explaining shared and non-shared etiology factors. The exclusive link between the general dysregulation factor and adolescents' self-harm and suicidal ideation further established the clinical relevance of the bifactor model.


Prognostic Value of Combination of Plasma D-Dimer Concentration and Estimated Glomerular Filtration Rate in Predicting Long-Term Mortality of Patients With Stable Coronary Artery Disease.
A modestly elevated circulating D-dimer level may be relevant to coronary artery disease (CAD), but its prognostic value, both independently and in combination with estimated glomerular filtration rate (eGFR), for long-term death has not been fully evaluated in stable CAD patients.Methods and Results:Baseline plasma D-dimer levels and eGFR were measured in 1,341 outpatients (mean age: 65 years) with prior myocardial infarction (MI), coronary revascularization, and/or angiographic evidence of a significant stenosis (>50%) for at least one of the major coronary arteries. Among these patients, 43% had prior MI, 47% had prior coronary revascularization, 41% had multivessel CAD, 14% had paroxysmal or persistent atrial fibrillation, 32% had diabetes, and 32% had chronic kidney disease (eGFR <60 mL/min/1.73 m2). D-dimer levels weakly correlated with eGFR (r=-0.25; P<0.0001). During a mean follow-up period of 73 months, there were 124 deaths, including 61 cardiovascular deaths. Multivariate Cox regression analysis identified D-dimer levels (P=0.001) and eGFR (P=0.006) as independent predictors of all-cause death. Adding both D-dimer and eGFR to a baseline model with established risk factors improved the net reclassification (P<0.005) and integrated discrimination improvement (P<0.05) greater than that of any single biomarker or baseline model alone. The combinatorial value of assessing D-dimer levels and eGFR may provide useful insight regarding stable CAD patients' long-term risk stratification.


Cohabitation history, marriage, and wealth accumulation.
This study extends research on the relationship between wealth accumulation and union experiences, such as marriage and cohabitation. Using data from the National Longitudinal Survey of Youth 1979, we explore the wealth trajectories of married individuals in light of their premarital cohabitation histories. Over time, marriage positively correlates with wealth accumulation. Most married persons with a premarital cohabitation history have wealth trajectories that are indistinguishable from those without cohabitation experience, with one exception: individuals who marry their one and only cohabiting partner experience a wealth premium that is twice as large as that for married individuals who never cohabited prior to marrying. Results remain robust over time despite cohabiters' selection out of marriage, yet vary by race/ethnicity. We conclude that relationship history may shape long-term wealth accumulation, and contrary to existing literature, individuals who marry their only cohabiting partners experience a beneficial marital outcome. It is therefore important to understand the diversity of cohabitation experiences among the married.


Imbalance in multiple sclerosis: a result of slowed spinal somatosensory conduction.
Balance problems and falls are common in people with multiple sclerosis (MS) but their cause and nature are not well understood. It is known that MS affects many areas of the central nervous system that can impact postural responses to maintain balance, including the cerebellum and the spinal cord. Cerebellar balance disorders are associated with normal latencies but reduced scaling of postural responses. We therefore examined the latency and scaling of automatic postural responses, and their relationship to somatosensory evoked potentials (SSEPs), in ten people with MS and imbalance and ten age-, sex-matched, healthy controls. The latency and scaling of postural responses to backward surface translations of five different velocities and amplitudes, and the latency of spinal and supraspinal somatosensory conduction, were examined. Subjects with MS had large, but very delayed automatic postural response latencies compared to controls (161 +/- 31 ms vs. 102 +/- 21 ms, p < 0.01) and these postural response latencies correlated with the latencies of their spinal SSEPs (r = 0.73, p < 0.01). Subjects with MS also had normal or excessive scaling of postural response amplitude to perturbation velocity and amplitude. Longer latency postural responses were associated with less velocity scaling and more amplitude scaling. Balance deficits in people with MS appear to be caused by slowed spinal somatosensory conduction and not by cerebellar involvement. People with MS appear to compensate for their slowed spinal somatosensory conduction by increasing the amplitude scaling and the magnitude of their postural responses.