Effectiveness of eHealth Interventions in Improving Treatment Adherence for Adults With Obstructive Sleep Apnea: Meta-Analytic Review.
Poor adherence to continuous positive airway pressure (CPAP) treatment by adults with obstructive sleep apnea (OSA) is a common issue. Strategies delivered by means of information and communication technologies (ie, eHealth) can address treatment adherence through patient education, real-time monitoring of apnea symptoms and CPAP adherence in daily life, self-management, and early identification and subsequent intervention when device or treatment problems arise. However, the effectiveness of available eHealth technologies in improving CPAP adherence has not yet been systematically studied. This meta-analytic review was designed to investigate the effectiveness of a broad range of eHealth interventions in improving CPAP treatment adherence. We conducted a systematic literature search of the databases of Cochrane Library, PsycINFO, PubMed, and Embase to identify relevant randomized controlled trials in adult OSA populations. The risk of bias in included studies was examined using seven items of the Cochrane Collaboration risk-of-bias tool. The meta-analysis was conducted with comprehensive meta-analysis software that computed differences in mean postintervention adherence (MD), which was defined as the average number of nightly hours of CPAP use. The meta-analysis ultimately included 18 studies (N=5429 adults with OSA) comprising 22 comparisons between experimental and control conditions. Postintervention data were assessed at 1 to 6 months after baseline, depending on the length of the experimental intervention. eHealth interventions increased the average nightly use of CPAP in hours as compared with care as usual (MD=0.54, 95% CI 0.29-0.79). Subgroup analyses did not reveal significant differences in effects between studies that used eHealth as an add-on or as a replacement to care as usual (P=.95), between studies that assessed stand-alone eHealth and blended strategies combining eHealth with face-to-face care (P=.23), or between studies of fully automated interventions and guided eHealth interventions (P=.83). Evidence for the long-term follow-up effectiveness of eHealth adherence interventions remains undecided owing to a scarcity of available studies and their mixed results. eHealth interventions for adults with OSA can improve adherence to CPAP in the initial months after the start of treatment, increasing the mean nightly duration of use by about half an hour. Uncertainty still exists regarding the timing, duration, intensity, and specific types of eHealth interventions that could be most effectively implemented by health care providers.


Diaquabis(2,5-dihydroxybenzoato-kappaO)bis(1,10-phenanthroline-kappa2N,N')strontium(II) bis(1,10-phenanthroline) tetrahydrate.
The title compound, [Sr(C(7)H(5)O(4))(2)(C(12)H(8)N(2))(2)(H(2)O)(2)].2C(12)H(8)N(2).4H(2)O, consists of an Sr(II) complex, uncoordinated phenanthroline (phen) molecules and solvent water molecules. The Sr(II) ion is located on a twofold axis and is coordinated by two phen ligands, two dihydroxybenzoate anions and two water molecules in a distorted tetragonal antiprismatic geometry. Partially overlapped arrangements exist between parallel coordinated and parallel uncoordinated phen rings; the face-to-face separations between the former (coordinated) and the latter (uncoordinated) rings are 3.436 (13) and 3.550 (14) A, respectively. This difference suggests the effect of metal coordination on pi-pi stacking between phen rings.


Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers.
Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch plus placebo, 28% and 7%. Despite the lack of a treatment effect, a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time. Similarly, an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking. These findings are encouraging and suggest new avenues for research. For example, treatments of the kind examined in this report, augmented by extended maintenance therapies, may yield higher long-term success rates.


Psychometric examination and normative data for the narcissistic personality inventory 29 item version.
The Narcissistic Personality Inventory (NPI) is commonly used in empirical studies of narcissism. Few population-based studies have been published. Our aim was to do a confirmatory factor analysis (CFA) of the NPI 29 item version with a four-factor structure, in two population-based samples and in a patient sample, and present normative population-based data. The NPI-29 was filled in by 324 respondents from the Norwegian population, 231 from the Swedish population and 167 Norwegian psychiatric patients. The four-factor structure of the NPI-29 with Leadership/Power, Exhibitionism/Self-admiration, Superiority/Arrogance and Uniqueness/Entitlement was reproduced in these samples. The CFA models showed good fit indices in all samples. Mean scores on the NPI-29 and four subscales hardly differed between the samples. For the NPI-29 total score and factors, few significant differences were observed. CFA of the samples supported the factor structure of the NPI-29 formerly identified by principal component analysis of the Swedish population sample.


Two chondrosarcomas in the urethra of a German shepherd dog.
An eight-year-old, male castrated German shepherd dog was presented with signs consistent with urinary obstruction. Cystoscopy and contrast radiography showed two distinct urethral masses. Penile amputation and perineal urethrostomy were performed to alleviate the clinical signs. Histopathology of the masses revealed two low-grade chondrosarcomas. At the time of writing, 18 months after surgery, the dog remained disease free.


Granisetron in repeated cycles of chemotherapy with platinum.
The aim of the present study was to assess the antiemetic efficacy of granisetron in repeated cycles of chemotherapy with platinum derivatives. The study included 50 patients (28 females, 22 males; aged 17-72, mean age 51 years). From 2 to 5 cycles of chemotherapy with cisplatin or carboplatin were performed. Granisetron was administered intravenously at a dose of 3 mg, 5 minutes before commencement of cytostatic chemotherapy. In case of 2 episodes of vomiting and severe nausea 2 additional doses of granisetron were given. Total control of emesis was achieved in 60% of patients after the first cycle of chemotherapy, and this percentage did not change significantly over the 5 cycles of chemotherapy. There were no differences in the antiemetic efficacy of granisetron in relation to patient sex up to cycle III, while in cycles IV and V a tendency towards less efficacy in females was observed. The adverse effects (headache, dizziness) were observed with the same frequency in the first 3 cycles of chemotherapy, while these were absent in cycles IV and V. Severe side effects were recorded only in cycle I, after that they were less expressed. In conclusion, granisetron is highly effective in prevention of emesis, induced by platinum derivatives and its efficacy is maintained over repeated cycles of chemotherapy. The toxicity of granisetron is mostly expressed in the first cycle, while after that it decreases significantly.


Recurrent neural network control for LCC-resonant ultrasonic motor drive.
A newly designed driving circuit for the traveling wave-type ultrasonic motor (USM), which consists of a push-pull DC-DC power converter and a two-phase voltage source inverter using one inductance and two capacitances (LCC) resonant technique, is presented in this study. Moreover, because the dynamic characteristics of the USM are difficult to obtain and the motor parameters are time varying, a recurrent neural network (RNN) controller is proposed to control the USM drive system. In the proposed controller, the dynamic backpropagation algorithm is adopted to train the RNN on-line using the proposed delta adaptation law. Furthermore, to guarantee the convergence of tracking error, analytical methods based on a discrete-type Lyapunov function are proposed to determine the varied learning rates for the training of the RNN. Finally, the effectiveness of the RNN-controlled USM drive system is demonstrated by some experimental results.


Insights into head and neck cancer research in Egypt: A scoping review.
Head and neck cancer (HNC) encompasses malignant tumors in areas like the oral cavity, pharynx, and larynx. This analysis identifies strengths and deficiencies in HNC research, aiming to improve published papers' quality, quantity, and diversity. It also encourages more participation from oncologists, particularly in Egypt, to bridge the gap with Western healthcare standards. A systematic search was conducted in databases including PubMed, Scopus, Web of Science, and Embase. The goal was to gather research articles on HNC in Egypt published from January 1, 2000, to December 31, 2022. From 2150 articles, 1329 were screened by title and abstract, leading to 193 for full-text review. Finally, 174 articles were included in the final analysis. 2020 saw the highest number of publications. The majority were primary research articles, with randomized controlled trials being prevalent. Most studies were clinical, focusing on radiotherapy, and involved adult patients, emphasizing service delivery. Publications were predominantly in non-Egyptian journals, with the Egyptian Journal of Radiology and Nuclear Medicine being the most frequent. Research was mainly conducted by Egyptian authors and at Cairo University. The growing prevalence of HNC in Egypt underscores the need for more comprehensive research on its various aspects, including etiology, risk factors, and prevention. There's a call for increased research outputs at different Egyptian universities, multicenter studies, and international collaborations. This approach can improve the understanding and management of HNC, contributing to global discussions and advancing treatment and prevention strategies in Egypt.


A horizon scan for species conservation by zoos and aquariums.
We conducted the first horizon scan for zoos and aquariums to identify the 10 most important emerging issues for species conservation. This involved input from more than 100 experts from both the wider conservation community and the world zoo and aquarium community. Some of the issues are globally important: diseases, zoonoses, and biosecurity issues; new (communication) technologies; global water shortage and food insecurity; developing economies and markets for wildlife consumption; changes in wildlife population dynamics; and political instability and conflicts. Other issues are more specific to zoos and aquariums: need for extractive reserves; space shortage in zoos and aquariums; need for metapopulation management; and demand for caring of more species in zoos and aquariums. We also identified some broad approaches to these issues. Addressing the emerging issues identified in our horizon scan will further increase the contribution of the world zoo and aquarium community to global biodiversity conservation.


A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies.
Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.


Combined functional oral rehabilitation after radical cancer surgery.
Formerly, patients requiring extensive reconstruction of the oral cavity and oropharynx after radical, ablative oncologic surgery faced the unhappy prospect of lengthy, multistaged repair to enjoy acceptable cosmesis and a functional oral cavity. The advent of the pectoralis major myocutaneous flap has made soft-tissue, single-stage closure of large oral cavity and oropharyngeal defects a reality. Unfortunately and frequently, restoration of mucocutaneous continuity of the mouth does not result in acceptable function. Advances in the materials and design of prostheses suggested the combination of myocutaneous flap reconstruction and functional, prosthetic restoration as a method of returning the patient with head and neck cancer to a state of acceptable function and appearance soon after major resection.


Actor and partner effects of self-rated health on life satisfaction among family caregiver couples.
This study examined the dyadic effects of self-rated health on the life satisfaction of family caregivers. The effects of the use of long-term care services were also explored to investigate whether support through care services is associated with the life satisfaction of family caregivers. The data were drawn from the sixth wave (2016) of the Korean Longitudinal Study of Aging. Caregivers who used long-term care services for older family members, and spouses of the caregivers, were identified. A total of 81 married caregiver couples were analyzed using the actor-partner interdependence model. The study showed that better self-rated health of caregivers was associated with higher levels of life satisfaction (B = 8.87, p < 0.001). Better self-rated health of the caregivers was also associated with higher life satisfaction of their spouses (B = 6.01, p < 0.05). In addition, the results suggested that the use of long-term care services for patients was associated with the life satisfaction of both caregivers (B = 14.57, p < 0.01) and their spouses (B = 12.51, p < 0.05). Our findings suggested mutual influences among family caregivers on their life satisfaction. In addition, long-term care services for patients may improve the life satisfaction of other family members. More support through long-term care services for people with care needs is required to increase the life satisfaction of family caregivers. The diverse relationships among family caregivers should be taken into consideration when developing policies and interventions.


Recovery from impaired working memory performance during chronic Δ-9-tetrahydrocannabinol administration to adolescent rhesus monkeys.
The relationship between adolescent cannabis use and susceptibility to persistent cognitive impairments is poorly understood. We examined the effects of repeated exposure to Δ-9-tetrahydrocannabinol (THC) on reinforcement-related learning and performance of spatial working memory (WM) tasks of varying difficulty in adolescent monkeys. Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 12 months. Performance on 4-item spatial WM trials was assessed throughout the 12-month study period. At the 6-month time point, more difficult novel and distractor 8-item spatial WM trials were added. Residual effects on performance were determined 23 or 71 h after THC or vehicle administration throughout the study. Relative to vehicle-exposed animals, repeated THC exposure was initially associated with significantly slower improvement in performance accuracy on 4-item spatial WM trials; however, this performance difference gradually diminished such that by month 12, accuracy did not significantly differ between vehicle and THC groups. Similarly, for the novel and distractor 8-item trials introduced at month 6, performance accuracy improved more slowly in the THC than in the vehicle group, despite comparable performance between groups on the 4-item task during this same period. These findings suggest that compared to vehicle exposure, THC exposure during adolescence impairs the reinforcement-related learning process required for improved performance on spatial WM tasks, but this impairment might be overcome with continued training, even in the face of ongoing THC exposure.


Self-assembled coatings on individual monodisperse magnetite nanoparticles for efficient intracellular uptake.
Monodispersed iron oxide superparamagnetic nanoparticles were prepared using a novel circulating system. A simple dialysis method was developed to immobilize nanoparticles with functional biopolymers and targeting agents, which avoids the use of the normal centrifugation process that may cause particle agglomeration during the coating process. To enhance the specific targeting capability of the nanoparticles, a new chemical scheme was introduced, in which folic acid (FA) was chosen as the targeting agent combined with PEG serving to improve biocompatibility of nanoparticles. The AFM characterization showed that the nanoparticles produced are well dispersed with a narrow size distribution. The FTIR and XPS spectrum analyses indicated that PEG and FA-PEG have been chemically/covalently bonded to nanoparticles using synthetic approach introduced in this study. Our biological study showed that coating nanoparticles with PEG-FA significantly enhanced the intracellular uptake of nanoparticles by target cells.


Rapid and ultrarapid opioid detoxification techniques.
To review the scientific literature on the effectiveness of rapid opioid detoxification (RD) (opioid withdrawal precipitated by naloxone hydrochloride or naltrexone) and ultrarapid opioid detoxification (URD) (opioid withdrawal precipitated by naloxone or naltrexone under anesthesia or heavy sedation) techniques. The MEDLINE database was searched from 1966 through 1997 using the indexing terms naloxone, naltrexone, substance dependence, and substance withdrawal syndrome. Additional data sources included bibliographies of papers identified on MEDLINE and bibliographies in textbooks on substance abuse. Inclusion criteria were studies of RD or URD, pharmacologic protocols specified, and clinical outcomes specified and reported. Exclusion criteria were unpublished data, data not in peer-reviewed journals, abstract-only publications, and review articles. The methodologic characteristics of studies were extracted by the authors and summarized according to key components of research design concerning subject characteristics, therapy allocation, and outcomes assessed. A qualitative analysis was performed on the 12 studies of RD and the 9 studies of URD identified in our search. The RD studies enrolled 641 subjects (range for individual studies, 1-162): 7 were inpatient studies, and the protocols varied considerably, as did the outcomes assessed. Three RD studies included a control group, 2 used a randomized design, and 3 reported outcomes beyond 12 days. The URD studies enrolled 424 subjects (range for individual studies, 6-300): all were inpatient studies, the detoxification and anesthesia protocols varied, 3 included a control group, 2 used a randomized design, and 2 reported outcomes for URD beyond 7 days. The existing literature on RD and URD is limited in terms of the number of subjects evaluated, the variation in protocols studied, lack of randomized design and use of control groups, and the short-term nature of the outcomes reported. Further research is needed using more rigorous research methods, longer-term outcomes, and comparisons with other methods of treatment for opioid dependence.


The use of the CO 2 laser in oral and maxillofacial surgery.
The CO 2 laser has a decided advantage in removing tumors of the oral cavity. This advantage is related to its ability to perform accurate hemostatic surgery, while at the same time sterilizing the operative area. During the past 4 years, 376 patients have been treated with the CO 2 laser (Sharplan 1040) at our hospital. A variety of benign oral lesions, malignant tumors, vascular tumors, preprosthetic surgery, and other oral lesions have been treated.


Craniocervical Junction Dural Arteriovenous Fistula and Pial Arteriovenous Fistula Presenting Concomitantly in Separate Locations with Subarachnoid Hemorrhage.
Craniocervical junction dural arteriovenous fistula and pial arteriovenous fistula are rare cerebrovascular lesions. While their pathophysiology is different, both conditions can cause intracranial hemorrhage attributable to venous congestion. We present, to our knowledge, the first case report of craniocervical junction dural arteriovenous fistula and pial arteriovenous fistula presenting concomitantly in separate locations with subarachnoid hemorrhage. This case appears to have been due to increased venous hypertension caused by a merging of the venous drainage of the 2 lesions, resulting in hemorrhage.


p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development.
During endochondral bone development, both the chondrogenic differentiation of mesenchyme and the hypertrophic differentiation of chondrocytes coincide with the proliferative arrest of the differentiating cells. However, the mechanisms by which differentiation is coordinated with cell cycle withdrawal, and the importance of this coordination for skeletal development, have not been defined. Through analysis of mice lacking the pRB-related p107 and p130 proteins, we found that p107 was required in prechondrogenic condensations for cell cycle withdrawal and for quantitatively normal alpha1(II) collagen expression. Remarkably, the p107-dependent proliferative arrest of mesenchymal cells was not needed for qualitative changes that are associated with chondrogenic differentiation, including production of Alcian blue-staining matrix and expression of the collagen IIB isoform. In chondrocytes, both p107 and p130 contributed to cell cycle exit, and p107 and p130 loss was accompanied by deregulated proliferation, reduced expression of Cbfa1, and reduced expression of Cbfa1-dependent genes that are associated with hypertrophic differentiation. Moreover, Cbfa1 was detected, and hypertrophic differentiation occurred, only in chondrocytes that had undergone or were undergoing a proliferative arrest. The results suggest that Cbfa1 links a p107- and p130-mediated cell cycle arrest to chondrocyte terminal differentiation.


Photostimulation of lymphatic clearance of β-amyloid from mouse brain: a new strategy for the therapy of Alzheimer's disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of β-amyloid (Aβ) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aβ plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aβ from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aβ clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aβ from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD.


Designing nanogadgets by interconnecting carbon nanotubes with zinc layers.
Using first-principles calculations we propose a new approach for the design of functional units obtained by interconnecting carbon nanotubes (CNTs) with different numbers of zinc layers. The theoretical investigations on electron transport properties of the resulting 1D heterojunctions containing CNTs with same or different chiralities (i.e., metallic or semiconducting) and one, two, or three zinc layers illustrate that the junctions with two semiconducting CNTs show semiconducting I-V characteristics while the junctions with two different CNT electrodes (metallic and semiconducting) show rectifying diode properties. The remarkable features emerging from this study is that the zinc layers behave as a momentum filter (near the Fermi energy the Bloch states having the same orbital character as the molecular states conduct well) when they are inserted within metallic CNT electrodes thereby providing 1D heterojunctions that can act as a wire-like, negative differential resistance (NDR), or varistor-type nanoscale device. Our results prove the idea that it is possible to design specific heterojunctions, which can select a conducting channel between two electrodes. Also, it is worth mentioning that in this study for the first time we have designed a nanoscale device with the characteristics of a varistor.


Diplomatic Assistance: Can Helminth-Modulated Macrophages Act as Treatment for Inflammatory Disease?
Helminths have evolved numerous pathways to prevent their expulsion or elimination from the host to ensure long-term survival. During infection, they target numerous host cells, including macrophages, to induce an alternatively activated phenotype, which aids elimination of infection, tissue repair, and wound healing. Multiple animal-based studies have demonstrated a significant reduction or complete reversal of disease by helminth infection, treatment with helminth products, or helminth-modulated macrophages in models of allergy, autoimmunity, and sepsis. Experimental studies of macrophage and helminth therapies are being translated into clinical benefits for patients undergoing transplantation and those with multiple sclerosis. Thus, helminths or helminth-modulated macrophages present great possibilities as therapeutic applications for inflammatory diseases in humans. Macrophage-based helminth therapies and the underlying mechanisms of their therapeutic or curative effects represent an under-researched area with the potential to open new avenues of treatment. This review explores the application of helminth-modulated macrophages as a new therapy for inflammatory diseases.


A North American stem turaco, and the complex biogeographic history of modern birds.
Earth's lower latitudes boast the majority of extant avian species-level and higher-order diversity, with many deeply diverging clades restricted to vestiges of Gondwana. However, palaeontological analyses reveal that many avian crown clades with restricted extant distributions had stem group relatives in very different parts of the world. Our phylogenetic analyses support the enigmatic fossil bird Foro panarium Olson 1992 from the early Eocene (Wasatchian) of Wyoming as a stem turaco (Neornithes: Pan-Musophagidae), a clade that is presently endemic to sub-Saharan Africa. Our analyses offer the first well-supported evidence for a stem musophagid (and therefore a useful fossil calibration for avian molecular divergence analyses), and reveal surprising new information on the early morphology and biogeography of this clade. Total-clade Musophagidae is identified as a potential participant in dispersal via the recently proposed 'North American Gateway' during the Palaeogene, and new biogeographic analyses illustrate the importance of the fossil record in revealing the complex historical biogeography of crown birds across geological timescales. In the Palaeogene, total-clade Musophagidae was distributed well outside the range of crown Musophagidae in the present day. This observation is consistent with similar biogeographic observations for numerous other modern bird clades, illustrating shortcomings of historical biogeographic analyses that do not incorporate information from the avian fossil record.


Mental ill health in structural pathways to women's experiences of intimate partner violence.
Depression, post-traumatic stress disorder (PTSD), and binge drinking are among mental health effects of child abuse and intimate partner violence (IPV) experiences among women. Emerging data show the potential mediating role of mental ill health in the relationship of child abuse and IPV. There is evidence that PTSD, depression and alcohol abuse are comorbid common mental disorders and that a bidirectional relationship exists between depression and IPV in some settings. Furthermore, the temporal direction in the relationship of alcohol abuse and women's IPV experiences from different studies is unclear. We undertook a study with women from the general population to investigate the associations of child abuse, mental ill health and IPV; and describe the underlying pathways between them. Data is from a household survey employing a multi-stage random sampling approach with 511 women from Gauteng, South Africa. IPV was measured using the WHO Multi-country Study on Women's Health and Domestic Violence Questionnaire. Child abuse was measured using a short form of the Childhood Trauma Questionnaire. Depression was measured using the Centre for Epidemiologic Studies Depression Scale (CESD). PTSD symptoms were measured using the Harvard Trauma Questionnaire. Binge drinking was measured using the Alcohol Use Disorders Identification Test (AUDIT) scale. All data analyses were conducted in Stata 13. Regression modelling was used to test the association between variables. Structural equation modelling with full information maximum likelihood estimation accounting for missing data was done to analyse the underlying pathways between variables. Fifty percent of women experienced IPV in their lifetime and 18% experienced IPV in the 12 months before the survey. Twenty three percent of women were depressed, 14% binge drank and 11.6% had PTSD symptoms. Eighty six percent of women had experienced some form of child abuse. Sociodemographic factors associated with recent IPV in multivariate models were younger age and foreign nationality. Depression, PTSD and binge drinking mediated the relationship of child abuse and recent IPV. Depression, PTSD and binge drinking were also effects of recent IPV. Other factors associated with recent IPV experience included relationship control, having a partner who regularly consumed alcohol and experiencing other life traumatic experiences. Mental ill health plays a mediating role in the relationship of child abuse and recent IPV experiences among women. Conversely, IPV also negatively affects women's mental health. Interventions to reducing the incidence of IPV could help alleviate the burden of mental ill health among women and vice versa. Effective integration of mental health services in primary health care, detection of symptoms, brief interventions and strengthened referral mechanisms for sustained community-based care are necessary in responding to victims of intimate partner violence. Response for abused children needs to take similar approaches and reduce the long-term mental health effects associated with violent exposures.


Modulation transfer function of a lens measured with a random target method.
We measured the modulation transfer function (MTF) of a lens in the visible region using a random test target generated on a computer screen. This is a simple method to determine the entire MTF curve in one measurement. The lens was obscured by several masks so that the measurements could be compared with the theoretically calculated MTF. Excellent agreement was obtained. Measurement noise was reduced by use of a large number of targets generated on the screen.


Comparison of two methods for the separation of polar from nonpolar lipids.
The countercurrent extraction method of Galanos and Kapoulas for the separation of phospholipids from triglycerides was compared with dialysis in petroleum ether in an apparatus modified from that of Eberhagen and Betzing. The efficiencies of the methods are similar, but dialysis, which is slower, can yield triglycerides that are entirely free from phosphorus. The behavior of free fatty acids and monoglycerides is also described.


Modeling stochastic dynamics in biochemical systems with feedback using maximum caliber.
Complex feedback systems are ubiquitous in biology. Modeling such systems with mass action laws or master equations requires information rarely measured directly. Thus rates and reaction topologies are often treated as adjustable parameters. Here we present a general stochastic modeling method for small chemical and biochemical systems with emphasis on feedback systems. The method, Maximum Caliber (MaxCal), is more parsimonious than others in constructing dynamical models requiring fewer model assumptions and parameters to capture the effects of feedback. MaxCal is the dynamical analogue of Maximum Entropy. It uses average rate quantities and correlations obtained from short experimental trajectories to construct dynamical models. We illustrate the method on the bistable genetic toggle switch. To test our method, we generate synthetic data from an underlying stochastic model. MaxCal reliably infers the statistics of the stochastic bistability and other full dynamical distributions of the simulated data, without having to invoke complex reaction schemes. The method should be broadly applicable to other systems.


The Arabidopsis phytochrome-interacting factor PIF7, together with PIF3 and PIF4, regulates responses to prolonged red light by modulating phyB levels.
We show that a previously uncharacterized Arabidopsis thaliana basic helix-loop-helix (bHLH) phytochrome interacting factor (PIF), designated PIF7, interacts specifically with the far-red light-absorbing Pfr form of phyB through a conserved domain called the active phyB binding motif. Similar to PIF3, upon light exposure, PIF7 rapidly migrates to intranuclear speckles, where it colocalizes with phyB. However, in striking contrast to PIF3, this process is not accompanied by detectable light-induced phosphorylation or degradation of PIF7, suggesting that the consequences of interaction with photoactivated phyB may differ among PIFs. Nevertheless, PIF7 acts similarly to PIF3 in prolonged red light as a weak negative regulator of phyB-mediated seedling deetiolation. Examination of pif3, pif4, and pif7 double mutant combinations shows that their moderate hypersensitivity to extended red light is additive. We provide evidence that the mechanism by which these PIFs operate on the phyB signaling pathway under prolonged red light is through maintaining low phyB protein levels, in an additive or synergistic manner, via a process likely involving the proteasome pathway. These data suggest that the role of these phyB-interacting bHLH factors in modulating seedling deetiolation in prolonged red light may not be as phy-activated signaling intermediates, as proposed previously, but as direct modulators of the abundance of the photoreceptor.


[Prognostic value of inverted papilloma of the lower urinary tract].
Inverted papilloma of the urothelium accounts for 2.2% of urothelial neoplasms. Its oncologic significance is unclear; its potential for recurrence and/or progression is not well-known. Our experience from 1976 to 1999 is reviewed. From 1976 to 1999, 31 patients with urothelial inverted papilloma of the lower urinary tract have been treated in our service: 17 presented previous and/or synchronous association with urothelial carcinoma (group I) and 14 had primary inverted papilloma (group II). The recurrence and progression rates for each group were determined and compared. The overall recurrence and progression rates were also determined. Two patients (one from each group) were lost to follow-up. The remaining 29 patients had a mean follow-up of 51.3 months (range 3-125). 12 patients (41.4%) showed recurrence in the form of bladder carcinoma; 10 from group I (10/16; 62.3%) and 2 from group II (2/13; 15.4%) (p < 0.05). Mean time to recurrence was 17.9 months (range 3-58). Disease free interval was higher in group II (p < 0.05). Progression to infiltrating tumor was observed in three patients; all three had associated superficial bladder carcinoma (group I). The mean time to progression was 30.7 months (range 18-38). No statistically significant differences were found in the percentage of progression between both groups. Inverted papilloma of the lower urinary tract showed a high incidence of association with urothelial carcinoma and a high recurrence rate, even in primary tumors. Therefore it should be considered a tumor of low grade malignancy that should be followed regularly.


Rural interprofessional service-learning: the Minnesota experience.
The Minnesota Rural Health School (MRHS), which operated from 1996 to 2003, was the University of Minnesota's first initiative that provided rural, community-based, interdisciplinary health professions education. The newly funded Minnesota Area Health Education Center (AHEC) is now coordinating interprofessional rural clinical education at the Academic Health Center level for the university. The service-learning curricular component is one of the most lasting legacies of the MRHS. This article provides a descriptive summary of the initial 61 service-learning projects completed by students from various health professions who participated in the MRHS and indicates the type of projects that have continuing effects. The seven community site coordinators affiliated with the MRHS completed a survey analyzing service-learning projects performed in their communities. Student interest was predominant in selecting 28% of the 61 projects, community interest was paramount in selecting 10%, and a mixture of both student and community interest contributed to 62% of project selection. Thirty of the projects were designed as single interventions, and the remaining 31 projects have ongoing impact. Students demonstrated interprofessional group synergy and significant creativity in addressing multiple community health care issues and needs, within time constraints of only ten to 12 days in which to develop and implement a service-learning project. Two project examples are described in detail to illustrate the challenges and successes of this type of civic engagement.


The Effects of Delirium Prevention Guidelines on Elderly Stroke Patients.
This study aimed to evaluate the effectiveness of the delirium prevention interventions recommended by the Delirium Prevention Guidelines for Elderly Stroke Patients (DPGESP). The DPGESP comprises nine dimensions with 28 interventions, including risk factor assessment, orientation disorder prevention, sleeping pattern maintenance, sensory interventions, constipation, dehydration, hypoxia and infection prevention, pain management, and appropriate nutrition maintenance. This quasi-experimental study used a nonequivalent control group and a pretest-posttest design. The experimental and control groups each included 54 patients, and the participants were elderly patients who were admitted to the stroke unit. The study outcomes were the delirium incidence and severity, stroke impact, and length of hospitalization. Posttest values for delirium incidence, severity, stroke impact, and length of hospitalization were significantly improved in the experimental group. Implementation of the DPGESP had beneficial effects on the delirium incidence and severity, stroke impact, and length of hospitalization among elderly patients admitted to a stroke unit.


Time-energy analysis of above-threshold ionization.
A Wigner-distribution-like function is proposed for analysis of the time-energy distribution of photoelectron emitted from an atom in intense laser fields. For the first time, the time-energy distribution of the photoelectron spectrum in above-threshold ionization is present. The interference pattern in the above-threshold ionization process in laser fields with different frequencies are investigated using the proposed method.


[Twelve years of the Baby-Friendly Hospital Initiative in Brazil].
To evaluate implementation of the Baby-Friendly Hospital Initiative (BFHI) in Brazil from 1992 to 2004. This retrospective descriptive study of the BFHI in Brazil examined the number of Baby-Friendly Hospitals (BFH) accredited per year from 1992 to 2004, state and regional distribution of the hospitals, the number of municipalities with a BFH, and the number of births at the 294 BFH that were participating in Brazil's universal, public health care system (Serviço Unico de Saúde) in 2004. Data were obtained from the Ministry of Health's Hospital Information System, from state health departments, and from Ministry of Health's reports on breastfeeding. From 1992 to 2004, a total of 312 hospitals were BFH-accredited across 24 of Brazil's 26 states and the Federal District. Of these, one had lost accreditation and 10 had been deactivated by the end of the study period. The regional distribution of the 301 remaining BFH in 2004 was: 139 in the Northeast, 59 in the Southeast, 50 in the South, 37 in the Midwest, and 16 in the North. A sharp drop in the accreditation rate was recorded in certain years: 1997, 2003, and 2004. In 2004, 294 (6.8%) of the 4,347 public hospitals with maternity beds were BFH. Of the 3 346 municipalities that had public hospitals with maternity beds, 205 (6.1%) also had BFH. In 2004, there were 2,227,971 births in public hospitals, of which 565,990 (25.4%) occurred in BFH. The number of BFH in Brazil is relatively small when compared to the number of public hospitals with maternity beds. The decreased accreditation rate and the deactivation of accredited BFH, especially in the latter years of the study, indicate the need for measures that will bolster and grow the BFHI in Brazil.


An engineered photoswitchable mammalian pyruvate kinase.
Changes in allosteric regulation of glycolytic enzymes have been linked to metabolic reprogramming involved in cancer. Remarkably, allosteric mechanisms control enzyme function at significantly shorter time-scales compared to the long-term effects of metabolic reprogramming on cell proliferation. It remains unclear if and how the speed and reversibility afforded by rapid allosteric control of metabolic enzymes is important for cell proliferation. Tools that allow specific, dynamic modulation of enzymatic activities in mammalian cells would help address this question. Towards this goal, we have used molecular dynamics simulations to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24]), an engineered pyruvate kinase M2 (PKM2) variant that harbours an insertion of the light-sensing LOV2 domain from Avena Sativa within a region implicated in allosteric regulation by fructose 1,6-bisphosphate (FBP). The LOV2 photoreaction is preserved in the PiL[D24] chimera and causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure. Importantly, this change in activity is reversible upon light withdrawal. Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose. PiL[D24] therefore could provide a means to modulate cellular glucose metabolism in a remote manner and paves the way for studying the importance of rapid allosteric phenomena in the regulation of metabolism and enzyme control.


Behavioural responses in a net restraint test predict interrenal reactivity in Arctic charr Salvelinus alpinus.
In this study, a 1 min net restraint test was evaluated as a method to predict stress-coping style in Arctic charr Salvelinus alpinus, by investigating the relationship between behaviour during the test and levels of plasma cortisol sampled after 30 min confinement. In two separate groups of S. alpinus, general linearized model revealed significant correlations between cortisol levels and principal component scores extracted from principal component analysis, combining measures of activity in the tests. With the use of glmulti, the model selection ruled out any effects of size, sex and order of capture on interrenal reactivity. In general, S. alpinus that were more active in the net restraint test also had low levels of circulating cortisol, suggesting a proactive coping style. The results from two repeated runs were not correlated, but both runs, performed eight days apart, show a negative correlation between post-stress cortisol level and activity in the net. The lack of consistency could be explained by different treatments before each run and individual differences in behavioural plasticity. The net restraint test is thus predictive of stress-coping style in S. alpinus, and has the benefit of being less time-consuming than the commonly used confinement stress test.


Autoinflammatory diseases in dermatology: DITRA and CAMPS.
Deficiency of interleukin thirty-six receptor antagonist (DITRA) and CARD14 mediated psoriasis (CAMPS) are autoinflammatory diseases in dermatology. The causative genes of DITRA and CMAPS have been identified recently. In this paper, IL36RN and CARD14, the causative gene for DITRA and CAMPS, respectively were explained. In addition, clinical features and therapies for generalized pustular psoriasis not associated with psoriasis vulgaris (GPP without PsV), and pityriasis rubra pilaris type V (PRP type V) were described. GPP without PsV and PRP type V are representative diseases of DITRA and CAMPS, respectively.


Infarction of Paratesticular Inflammatory Myofibroblastic Tumor Mimicking Testicular Torsion.
This report describes a 14-year-old male with a rare paratesticular inflammatory myofibroblastic tumor that presented atypically with acute unilateral scrotal pain and swelling. This presentation, which raised suspicion for testicular torsion, contrasts with the typical presentation of a slow-growing scrotal mass. Scrotal exploration revealed an infarcted right testis, demonstrating this locally aggressive tumor can undergo vascular invasion and occlude testicular blood supply. Thus, inflammatory myofibroblastic tumor should be considered in the differential diagnosis when evaluating patients with acute scrotal pain suspicious for testicular infarction.


Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides.
The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cycle exercise bout at 50% of their peak oxygen uptake on two occasions: during intravenous infusion of octreotide (a somatostatin analog) or physiological saline (control condition). Lipolysis in SCAT was evaluated using in situ microdialysis. One microdialysis probe was perfused with the adrenergic blockers phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from approximately 3.5 to 0.5 microU/ml) and in obese (from approximately 9 to 2 microU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects. The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups.


Design and demonstration of a vari-focal optical see-through head-mounted display using freeform Alvarez lenses.
Alvarez lenses offer accurate and high-speed, dynamic tuning of optical power through a lateral shifting of two lens elements, making them an appealing solution to eliminate the inherent decoupling of accommodation and convergence seen in conventional stereoscopic displays. In this paper, we present a design of a compact eyepiece coupled with two lateral-shifting freeform Alvarez lenses to enable a compact, high-resolution, optical see-through head-mounted display (HMD). The proposed design is able to tune its focal depth from 0 to 3 diopters, rendering near-accurate focus cues with high image quality and a large undistorted see-through field of view (FOV). Our design utilizes an 1920x1080 color resolution organic light-emitting diode (OLED) microdisplay to achieve a >30 degree virtual diagonal FOV, with an angular resolution of <0.85 arcminutes and an average optical performance of > 0.4 contrast over the full field. We also experimentally demonstrate a fully functional benchtop prototype using mostly off-the-shelf optics.


Laminin receptors on SCLC cells.
Several studies have suggested a correlation between the metastatic potential and the expression of adhesion molecules and/or their receptors on tumour cell surface membranes. In this study we investigated the expression of functional laminin receptors on small cell lung cancer (SCLC) cells. To this aim we set up an adherence assay to determine the in vitro binding capability of tumour cell lines to laminin. All of the three SCLC lines tested and cells from a short-term SCLC line adhered to laminin in cell culture plates, and the affinity of cell-matrix adhesion proved to be higher than the cell-cell adhesion. This effect was always laminin dose-dependent. On a laminin affinity chromatography column three major proteins could be eluted with EDTA from soluble extracts of SCLC lines. Their molecular weights of 120, 90 and 30 kDa suggested a possible relationship with the integrin family. This putative integrin laminin receptor expressed on SCLC does not react with fibronectin, vitronectin or collagen.


Past orientation of the lunar spin axis.
The orientation of the lunar spin axis is traced from the early history of the earth-moon system to the present day. Tides raised on the earth by the moon have caused an expansion of the lunar orbit. Tides raised on the moon by the earth have de-spun the moon to synchronous rotation and driven its spin axis to a Cassini state-that is, in a coprecessing configuration, coplanar with the lunar orbit normal and the normal to the Laplacian plane (which is at present coincident with the normal to the ecliptic). This combination of events has resulted in a complex history for the lunar spin axis. For much of the period during which its orbital semimajor axis expanded between 30 and 40 earth radii, the obliquity of the moon was of order 25 degrees to 50 degrees . In fact, for a brief period the obliquity periodically attained a value as high as 77 degrees ; that is, the spin axis of the moon was only 13 degrees from lying in its orbit plane.


New polymorphic microsatellite markers in the human MHC class I region.
The human major histocompatibility complex (MHC) class I region is believed to contain a large number of genes encoding susceptible factors for diseases such as Behcet's disease, Graves disease and psoriasis vulgaris. To identify the causative genes of those diseases, we have conducted large-scale genomic sequencing and determined the 1.8 Mb entire HLA class I region from the MICB gene to the HLA-F gene. During the course of genomic sequencing, a total of 731 microsatellite sequences with dinucleotide to pentanucleotide repeats were found in this region. Previously, we reported that 26 microsatellites between MICB and S on the most centromeric side of the class I region, and between HSR1 and HLA-92/L in the midst of the class I region were highly polymorphic, and served as excellent genetic markers. In this paper, in order to fill the gaps with no known polymorphic microsatellites available in the HLA class I region, 12 new polymorphic microsatellite markers were recruited from the 1.8 Mb region including the remaining class I segments, namely between S and HSR1, and between HLA-92/L and HLA-F The average number of alleles at these new microsatellite loci was 8.2 with a polymorphism content value (PIC) of 0.63. These 38 markers in total almost uniformly interspersed in the HLA class I region will enable us to search precisely for the location of disease susceptible loci within the HLA class I region by association and for linkage analyses.


Prevalence rate and associated factors of sarcopenic obesity in korean elderly population.
This study was conducted to estimate the prevalence rates and to explore associated factors of sarcopenic obesity (SO) in 2,221 Koreans over 60 yr-of age from the Fourth Korea National Health and Nutrition Examination Survey (2009). Participants were assessed by dual energy X-ray absorptiometry. Appendicular skeletal muscle mass divided by body weight was used to define sarcopenia and waist circumference was used to define obesity. We estimated the prevalence rates of SO according to age-groups, sex and region. In addition, each group was compared by demographic characteristics, metabolic status, nutrition, and physical activity. The prevalence rates of SO were 6.1% (95% confidential interval [CI] = 6.1-6.2) for men and 7.3% (95% CI = 7.3-7.3) for women, respectively. SO was positively associated with no current working and the number of combined medical conditions. High serum insulin level was positively associated with SO, whereas vitamin D was negatively associated with SO in both men and women. In conclusion, the prevalence rates of SO are 6.1% in men and 7.3% in women. SO is associated with insulin resistance, inappropriate nutrition, and low physical activity.


Wound-healing protocols for diabetic foot and pressure ulcers.
Diabetic foot and pressure ulcers are chronic wounds by definition. They share similar pathogeneses; i.e., a combination of increased pressure and decreased angiogenic response. Neuropathy, trauma, and deformity also often contribute to development of both types of ulcers. Early intervention and proper treatment should result in complete healing of non-ischemic diabetic foot and pressure ulcers, as defined by 100% epithelialization and no drainage (if no osteomyelitis is present). The authors developed the following paradigm, which has proved to be highly effective for complete healing of these wounds: 1) recognition that all patients with limited mobility are at risk for a sacral, ischial, trochanteric, or heel pressure ulcer; 2) daily self-examination of the sacral, ischium, buttocks, hips, and heels of all bed-bound patients and the feet of patients with diabetes with risk factors (e.g., neuropathy); 3) initiation of a treatment protocol immediately upon recognition of a break in the skin (i.e., emergence of a new wound); 4) objective measurement by planimetry of every wound (at a minimum, weekly) and documentation of its progress; 5) establishment of a moist wound-healing environment; 6) relief of pressure from the wound; 7) debridement of all non-viable tissue in the wound; 8) elimination of all drainage and cellulitis; 9) cellular therapy or growth factors for patients with wounds that do not heal rapidly after initial treatment; and 10) continuous physical and psychosocial support for all patients. If this paradigm is followed, most diabetic foot and pressure ulcers are expected to heal.


Cost sharing for antiepileptic drugs: medication utilization and health plan costs.
To examine the association between health plan out-of-pocket (OOP) costs for antiepileptic drugs and healthcare utilization (HCU) and overall plan spending among US-based commercial health plan beneficiaries with epilepsy. Retrospective cohort. The Truven MarketScan Commercial Claims database for January 1, 2009, to June 30, 2015, was used. Patients 65 years or younger with epilepsy and at least 12 months of continuous enrollment before index (date meeting first epilepsy diagnostic criteria) were included. Analyses were adjusted for age group, gender, beneficiary relationship, insurance plan type, and Charlson Comorbidity Index score. Primary outcomes included proportion of days covered (PDC), HCU, and healthcare spending in 90-day postindex periods. Associations between OOP costs and mean PDC, HCU, and plan healthcare spending per 90-day period were estimated. Across 5159 plans, 187,241 beneficiaries met eligibility criteria; 54.3% were female, 41.7% were aged 45 to 65 years, and 62.4% were in preferred provider organization plans. Across postindex 90-day periods, mean (SD) PDC, epilepsy-specific hospitalizations, outpatient visits, and emergency department visits were 0.85 (0.26), 0.02 (0.13), 0.34 (0.47), and 0.05 (0.22), respectively. Median (interquartile range) spending per 90-day period was $1488 ($459-$4705); median epilepsy-specific spending was $139 ($18-$623). Multivariable linear regression without health plan fixed effects revealed that higher OOP spending was associated with a decrease in PDC (coefficient, -0.008; 95% CI, -0.009 to -0.006; P <.001) and an increase in overall spending (218.6; 95% CI, 47.9-389.2; P = .012). Health plan fixed effects model estimates were similar, except for epilepsy-specific spending, which was significant (120.6; 95% CI, 29.2-211.9; P = .010). Increases in beneficiaries' OOP costs led to higher overall spending and lower PDC.


PET/CT-tailored treatment of locally advanced oesophago-gastric junction adenocarcinoma: a report on the feasibility of the multicenter GastroPET study.
Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I - III) stage Ib-IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with the same chemotherapy for 2 to 3 months prior to surgery. PET-non-responders switched to preoperative chemoradiotherapy [weekly carboplatin and paclitaxel with concurrent radiotherapy (45 Gy in 25 fractions)]. Here, we aim to confirm the feasibility of FDG-PET-based response assessment in a multicenter setting and to compare local versus central reading. In addition, we report on the feasibility of the study conduct and patient safety data. A total of 64 patients received baseline and sequential 14-day 18FDG-PET/CT scanning. And, 63 were allocated to the respective treatment arm according to PET-response [35 (56%) responders and 28 (44%) non-responders]. The concordance of local versus central reading of SUV changes was 100%. Until the date of this analysis, 47 patients (28 responders and 19 non-responders) completed surgery. Postoperative complications of grade ⩾ 3 (Common Terminology Criteria for Adverse Events, CTCAE Version 5.0) were reported in five responders (18%; 95% CI: 7.9-36%) and two non-responders (11%; 95% CI: 2.9-31%), with no statistical difference (p = 0.685). One patient in each arm died after surgery, leading to a postoperative in-hospital mortality rate of 4.3% (2/47 patients; 95% CI: 1.2-14%). Local and central FDG-SUV quantification and PET-response assessment showed high concordance. This confirms the accuracy of a PET-response-guided treatment algorithm for locally advanced oesophago-gastric junction cancer in a multicenter setting. Preoperative treatment adaptation revealed feasible and safe for patients.


[Development of Vital Signal Monitoring System Based on Accelerometer].
Reduce the number of false alarms and measurement time caused by movement interference by the sync waveform of the movement. Vital signal monitoring system based on motion sensor was developed, which collected and processed the vital signals continuously, optimized the features and results of vital signals and transmitted the vital signal results and alarms to the interface. The system was tested in many departments, such as digestive department, cardiology department, internal medicine department, hepatobiliary surgery department and emergency department, and the total collection time was 1 940 h. The number of false electrocardiograph (ECG) alarms decreased by 82.8%, and the proportion of correct alarms increased by 28%. The average measurement time of non-invasive blood pressure (NIBP) decreased by 16.1 s. The total number of false respiratory rate measurement decreased by 71.9%. False alarms and measurement failures can be avoided by the vital signal monitoring system based on accelerometer to reduce the alarm fatigue in clinic.


Cohort profile: a data linkage cohort to examine health service profiles of people with intellectual disability in New South Wales, Australia.
People with intellectual disability are a minority group who experience poorer physical and mental health than the general population and have difficulty accessing healthcare services. There is lack of knowledge about healthcare service needs and gaps experienced by people with intellectual disability. This study aims to interrogate a large linked administrative data set containing hospital admissions, presentations to emergency departments (ED) and mortality data to provide evidence to inform the development of improved health and mental health services for this population. A retrospective cohort of people with intellectual disability (n=51 452) from New South Wales (NSW), Australia, to explore health and mental health profiles, mortality, pattern of health service use and associated costs between 2005 and 2013. The cohort is drawn from: the Disability Services Minimum Data Set; Admitted Patients Data Collection; Emergency Department Data Collection, Australian Bureau of Statistics Death Registry and Registry of Births, Deaths and Marriages. Mental health service usage among those with intellectual disability will be compared to a cohort of people who used mental health services (n=1 073 139) and service usage other than for mental health will be compared with published data from the general population. The median age of the cohort was 24 at the time of the last hospital admission and 21 at the last ED presentation. The cohort has a higher proportion of men than women and accounts for 0.6% of the NSW population in 2011. Over 70% had up to 5 ED presentations and hospitalisations between 2005 and 2012. A high proportion of people with intellectual disability live in the most disadvantaged neighbourhoods. Results will be used to inform the development of more responsive healthcare, including improved interactions between health, social and disability supports. More generally, the results will assist the development of more inclusive policy frameworks for people with intellectual disability.


Expanding the pharmacological profile of κ-hefutoxin 1 and analogues: A focus on the inhibitory effect on the oncogenic channel Kv10.1.
Peptide toxins, such as scorpion peptides, are interesting lead compounds in the search for novel drugs. In this paper, the focus is on the scorpion peptide κ-hefutoxin 1. This peptide displays a cysteine-stabilized helix-loop-helix fold (CSα/α) and is known to be a weak Kv1.x inhibitor. Due to the low affinity of κ-hefutoxin 1 for these channels, it is assumed that the main target(s) of κ-hefutoxin 1 remain(s) unknown. In order to identify novel targets, electrophysiological measurements and antifungal assays were performed. The effect of κ-hefutoxin 1 was previously evaluated on a panel of 11 different voltage-gated potassium channels. Here, we extended this target screening with the oncogenic potassium channel Kv10.1. κ-Hefutoxin 1 was able to inhibit this channel in a dose-dependent manner (IC50∼26μM). Although the affinity is rather low, this is the first peptide toxin ever described to be a Kv10.1 inhibitor. The structure-activity relationship of κ-hefutoxin 1 on Kv10.1 was investigated by testing eight κ-hefutoxin 1 variants using the two-electrode voltage clamp technique. Several important amino acid residues were identified; the functional dyad residues (Tyr5 and Lys19), N-terminal residues (Gly1 and His2) and the amidated C-terminal residue (Cys22). Since the CSα/α fold is also found in a class of antifungal plant peptides, the α-hairpinines, we investigated the antifungal activity of κ-hefutoxin 1. κ-Hefutoxin 1 showed low activity against the plant pathogen Fusarium culmorum and no activity against three other yeast and fungal species, even at high concentrations (∼100μM).


Effective approaches to public engagement with global health topics.
"Public engagement" in science is a term that covers a broad spectrum of activities undertaken by the scientific community. The precise definitions are constantly evolving to incorporate new means of engagement, facilitated by emerging technologies. Global health research is amenable to community engagement and popularization, but it is difficult to know which strategies work best to attract considerable attention from the public. This is a review of the articles and documents that address the question of public engagement with topics in medical sciences, particularly in global health. Semantic searches were conducted using Google Scholar rather than indexed databases due to poor indexing of the topic. More than 1000 titles were screened and 48 articles were retained as most useful. It then moves to a more specific topic of the online public engagement in global health. The review presents the attempts to define public engagement in science and its general importance, particularly in the field of global health. Examples of the latter include tobacco use, vaccination, and maternal and child health. In reviewing effective approaches to public engagement in global health through online video campaigns, it studies the examples of crowdfunding, USAID's First Public Engagement Campaign, World Health Organization's Social Media Campaigns and the impact of Global Health Media Project. This review reveals three key gaps in the understanding of determinants of effective online public engagement in global health. The mixed results of traditional mass media campaigns in global health emphasise the calls for more research on message content. A framework for effective message content would help in both raising awareness of key issues and creating behaviour change in the general public. Moreover, it is surprising to find no formal research on what constitutes effective video content in global health. Finally, few studies considered important metrics to track in social media campaigns. There is a clear need to investigate which video features are effective in global health online public engagement. Success will be defined through key video marketing metrics and tracked in order to isolate effective content features.


Compartmentalized cAMP/PKA signalling regulates cardiac excitation-contraction coupling.
The sympathetic control over excitation-contraction coupling (ECC) is mediated by the cAMP/PKA signalling pathway. However, in the myocyte, the same signalling pathway is responsible for triggering a plethora of diverse intracellular functions the control of which must be independent of the regulation of ECC. Here we discuss what are the molecular mechanisms leading to selective modulation of ECC in cardiac myocytes with a particular focus on the role of spatial confinement of PKA subsets and the compartmentalization of cAMP.


Horizontal gene transfer and redundancy of tryptophan biosynthetic enzymes in dinotoms.
A tertiary endosymbiosis between a dinoflagellate host and diatom endosymbiont gave rise to "dinotoms," cells with a unique nuclear and mitochondrial redundancy derived from two evolutionarily distinct eukaryotic lineages. To examine how this unique redundancy might have affected the evolution of metabolic systems, we investigated the transcription of genes involved in biosynthesis of the amino acid tryptophan in three species, Durinskia baltica, Kryptoperidinium foliaceum, and Glenodinium foliaceum. From transcriptome sequence data, we recovered two distinct sets of protein-coding transcripts covering the entire tryptophan biosynthetic pathway. Phylogenetic analyses suggest a diatom origin for one set of the proteins, which we infer to be expressed in the endosymbiont, and that the other arose from multiple horizontal gene transfer events to the dinoflagellate ancestor of the host lineage. This is the first indication that these cells retain redundant sets of transcripts and likely metabolic pathways for the biosynthesis of small molecules and extend their redundancy to their two distinct nuclear genomes.


Development of hard masks for reactive ion beam angled etching of diamond.
Diamond offers good optical properties and hosts bright color centers with long spin coherence times. Recent advances in angled-etching of diamond, specifically with reactive ion beam angled etching (RIBAE), have led to successful demonstration of quantum photonic devices operating at visible wavelengths. However, larger devices operating at telecommunication wavelengths have been difficult to fabricate due to the increased mask erosion, arising from the increased size of devices requiring longer etch times. We evaluated different mask materials for RIBAE of diamond photonic crystal nanobeams and waveguides, and how their thickness, selectivity, aspect ratio and sidewall smoothness affected the resultant etch profiles and optical performance. We found that a thick hydrogen silesquioxane (HSQ) layer on a thin alumina adhesion layer provided the best etch profile and optical performance. The techniques explored in this work can also be adapted to other bulk materials that are not available heteroepitaxially or as thin films-on-insulator.


The management of meibomian gland carcinoma.
We present nine cases of sebaceous adenocarcinoma seen on the Oculoplastic Service at the University of Iowa over the past five years. It is essential to make the biopsy-proven diagnosis of meibomian gland adenocarcinoma promptly, using multiple full thickness eyelid biopsies. We recommend the Mohs' fresh-frozen technique in patients with surgically resectable lesions, exenteration in those with orbital extension, and radical neck dissection for cases with nodal involvement. Radiotherapy may be indicated in patients with extensive tumors who cannot tolerate or refuse surgery or as an adjunct to surgery in others.


Perceptions of health and healthcare in ex-Army residents of Tameside: a pilot qualitative study.
Local authorities and other service providers need data on their local ex-military communities to be able to plan services. However, published research and data may not be applicable to the local population. Qualitative research offers a relatively low-cost way to get insights into the needs of local ex-military communities. A pilot study using in-depth interviews with a small convenience sample of former ex-Army residents of Tameside. Framework analysis was used to identify and group themes arising from the data. This study was conducted using the Consolidated Criteria for Reporting Qualitative Research. While participants saw mental health as a particular challenge, they felt that it tends to get disproportionate attention relative to other needs. The study identified potential barriers to accessing health services that arise from an interaction between aspects of military and civilian healthcare culture and practices. Participants also said that military service could affect the health of both partners and children and that these effects might be more pronounced at key times, such as during adolescence. Participants' perceptions of the health of former members of the Armed forces reflect the published epidemiological literature. This suggests that qualitative data can be valid for understanding the health needs of local ex-military communities. Further research is needed to test the findings here with a broader group of ex-military personnel, to explore the barriers faced in accessing healthcare and to understand the health needs of the families of ex-service personnel.


The Effectiveness of Percutaneous Vertebroplasty Is Determined by the Patient-Specific Bone Condition and the Treatment Strategy.
Vertebral fragility fractures are often treated by injecting bone cement into the collapsed vertebral bodies (vertebroplasty). The mechanisms by which vertebroplasty induces pain relief are not completely understood yet and recent debates cast doubt over the outcome of the procedure. The controversy is intensified by inconsistent results of randomized clinical trials and biomechanical studies that have investigated the effectiveness or the change in biomechanical response due to the reinforcement. The purpose of this study was to evaluate the effectiveness of vertebroplasty, by varying the relevant treatment parameters and (a) computationally predicting the improvement of the fracture risk depending on the chosen treatment strategy, and (b) identifying the determinants of a successful treatment. A Finite Element model with a patient-specific failure criterion and direct simulation of PMMA infiltration in four lumbar vertebrae was used to assess the condition of the bone under compressive load before and after the virtual treatment, simulating in a total of 12000 virtual treatments. The results showed that vertebroplasty is capable of reducing the fracture risk by magnitudes, but can also have a detrimental effect. Effectiveness was strongly influenced by interactions between local bone quality, cement volume and injection location. However, only a moderate number of the investigated treatment strategies were able to achieve the necessary improvement for preventing a fracture. We conclude that the effectiveness of vertebroplasty is sensitive to the patient's condition and the treatment strategy.


CYP2D6 polymorphisms in Alzheimer's disease, with and without extrapyramidal signs, showing no apolipoprotein E epsilon 4 effect modification.
Allelic variation at the CYP2D6 gene has been reported to be associated with Parkinsons' disease (PD) and Lewy body dementia (LBD), but not with Alzheimer's disease (AD). AD has been associated with apolipoprotein E (apoE) epsilon 4 allele loading. We examined CYP2D6 and apoE polimorphisms in a sample of 259 patients with dementia, 210 of whom had a diagnosis of AD, and 107 healthy controls. We found that the allelic frequency in our AD sample did not vary from that in the controls. The debrisoquine hydroxylase poor metabolize phenotype was not more prevalent among AD cases than among controls in contrast to that reported for PD and LBD. We also found that CYP2D6 status does not modify the risk effect for AD conferred by apoE epsilon 4 alleles. These findings provide some support to the notion that, at a genetic level, at least at this locus, AD could be distinct from PD and LBD.


Results of surgical treatment of unresolved Osgood-Schlatter disease in adults.
Osgood-Schlatter is a common disease with most cases resolving spontaneously with skeletal maturity. Adults with continued symptoms may need surgical treatment if they fail to respond to conservative measures. The purpose of this study is to describe the pathological lesions, our surgical technique, and the results of our surgical treatment of Osgood Schlatter disease in adults. Thirty-five adult patients (37 knees) had surgery for unresolved Osgood-Schlatter disease. Three patients were lost for follow-up. An incision over the anterolateral aspect of the patellar tendon was used. Direct anterior incisions were avoided to decrease postoperative pain with kneeling. The patellar tendon was reflected medially, and the ossicle was removed from the posterior surface of the tendon. A tibial tuberosity reduction osteotomy was done in 29 cases (85%). A beak of the distal part of the tibial tubercle was found in 24 cases (71%) with impingement of the patellar ligament. Thirty-one knees (91%) had complete resolution of preoperative pain. There was one case of painful scar. This surgical technique for treatment of Osgood-Schlatter disease in adults is effective and safe especially for those who have the habit of frequent kneeling.


Sarcoidosis following specific immunotherapy: more than just coincidence?
Although not yet clear, the etiology of sarcoidosis may be linked to seasonal, environmental and genetic factors; mycobacterial or other infections. To the best of our knowledge there is no data suggesting any connection between the onset of sarcoidosis and specific allergen immunotherapy in the medical literature. During the 11-year period between 1993 and 2005, a total of 91 sarcoidosis cases have been diagnosed at our institution. Out of these, here we present 3 cases of de novo sarcoidosis occurring after receiving specific immunotherapy (SIT) at the same institution (two of which had acquired the disease in Sweden where they had resided for a short time). We suggest that sarcoidosis may occur in patients following (SIT) probably via an abnormal immunological host response to an unknown antigenic trigger.


The tailored sperm cell.
Sperm are ubiquitous and yet unique. Genes involved in sexual reproduction are more divergent than most genes expressed in non-reproductive tissues. It has been argued that sperm have been altered during evolution more than any somatic cell. Profound variations are found at the level of morphology, motility, search strategy for the egg, and the underlying signalling mechanisms. Sperm evolutionary adaptation may have arisen from sperm competition (sperm from rival males compete within the female's body to fertilize eggs), cryptic female choice (the female's ability to choose among different stored sperm), social cues tuning sperm quality or from the site of fertilization (internal vs. external fertilization), to name a few. Unquestionably, sperm represent an invaluable source for the exploration of biological diversity at the level of signalling, motility, and evolution. Despite the richness in sperm variations, only a few model systems for signalling and motility have been studied in detail. Using fast kinetic techniques, electrophysiological recordings, and optogenetics, the molecular players and the sequence of signalling events of sperm from a few marine invertebrates, mammals, and fish are being elucidated. Furthermore, recent technological advances allow studying sperm motility with unprecedented precision; these studies provide new insights into flagellar motility and navigation in three dimensions (3D). The scope of this review is to highlight variations in motile sperm across species, and discuss the great promise that 3D imaging techniques offer into unravelling sperm mysteries.


Macrophage activation-mediated hydrogen peroxide generation by the royal sun medicinal mushroom Agaricus brasiliensis (Higher Basidiomycetes).
Agaricus brasiliensis has been demonstrated to have potent antitumor activity. The activity is postulated to act through mediation of the host immune system. We have reported that A. brasiliensis extract (ABE) inhibited compound 48/80 induced a systemic anaphylaxis-like reaction, ear swelling response, and passive cutaneous anaphylaxis-like reaction in mice. There is some recent information available on the mechanism of antiallergic effects resulting from oral administration of ABE. However, information regarding how ABE may activate macrophages through intestinal epithelial cells is still limited. To clarify the mechanism of macrophages activation by ABE, a gut in vitro model constructed of Caco-2 and RAW264.7 cells was applied. Treatment of ABE to the apical compartment resulted in significant increases in tumor necrosis factor (TNF)-α production in the basolateral compartment. Moreover, addition of catalase to the basolateral compartment before ABE treatment suppressed TNF-α production completely, but the addition of superoxide dismutase did not suppress this at all. These data suggest that ABE could potentiate hydrogen peroxide emissions from Caco-2 cells into the basolateral side and activate macrophages, which is important in the immune system.


Different EGF-induced receptor dimer conformations for signaling and internalization.
The structural basis of the activation and internalization of EGF receptors (EGFR) is still a matter of debate despite the importance of this target in cancer treatment. Whether agonists induce dimer formation or act on preformed dimers remains discussed. Here, we provide direct evidence that EGF-induced EGFR dimer formation as best illustrated by the very large increase in FRET between snap-tagged EGFR subunits induced by agonists. We confirm that Erlotinib-related TK (tyrosine kinase) inhibitors also induce dimer formation despite the inactive state of the binding domain. Surprisingly, TK inhibitors do not inhibit EGF-induced EGFR internalization despite their ability to fully block EGFR signaling. Only Erlotinib-related TK inhibitors promoting asymmetric dimers could slow down this process while the lapatinib-related ones have almost no effect. These results reveal that the conformation of the intracellular TK dimer, rather than the known EGFR signaling, is critical for EGFR internalization. These results also illustrate clear differences in the mode of action of TK inhibitors on the EGFR and open novel possibilities to control EGFR signaling for cancer treatment.


Neurons expressing the highest levels of gamma-synuclein are unaffected by targeted inactivation of the gene.
Homologous recombination in ES cells was employed to generate mice with targeted deletion of the first three exons of the gamma-synuclein gene. Complete inactivation of gene expression in null mutant mice was confirmed on the mRNA and protein levels. Null mutant mice are viable, are fertile, and do not display evident phenotypical abnormalities. The effects of gamma-synuclein deficiency on motor and peripheral sensory neurons were studied by various methods in vivo and in vitro. These two types of neurons were selected because they both express high levels of gamma-synuclein from the early stages of mouse embryonic development but later in the development they display different patterns of intracellular compartmentalization of the protein. We found no difference in the number of neurons between wild-type and null mutant animals in several brain stem motor nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The survival of gamma-synuclein-deficient trigeminal neurons in various culture conditions was not different from that of wild-type neurons. There was no difference in the numbers of myelinated and nonmyelinated fibers in the saphenous nerves of these animals, and sensory reflex thresholds were also intact in gamma-synuclein null mutant mice. Nerve injury led to similar changes in sensory function in wild-type and mutant mice. Taken together, our data suggest that like alpha-synuclein, gamma-synuclein is dispensable for the development and function of the nervous system.


Vision and art: an interdisciplinary approach to neuroscience education.
Undergraduate institutions are increasingly adopting neuroscience within their curricula, although it is unclear how best to implement this material given the interdisciplinary nature of the field, which requires knowledge of basic physics, chemistry, biology and psychology. This difficulty is compounded by declines over recent decades in the amount of physics education that students receive in high school, which hinders students' ability to grasp basic principles of neuroscience. Here we discuss our experiences as teacher (BRC) and student (RLS) with an undergraduate course in Vision and Art. The course capitalizes on students' prior interest in visual art to motivate an understanding of the physiological and computational neural processes that underlie vision; our aim is that the learning strategies that students acquire as a result of the format and interdisciplinary approach of the course will increase students' critical thinking skills and benefit them as they pursue other domains of inquiry. The course includes both expert lectures on central themes of vision along with a problem-based learning (PBL) laboratory component that directly engages the students as empirical scientists. We outline the syllabus, the motivation for using PBL, and describe a number of hands-on laboratory exercises, many of which require only inexpensive and readily available equipment. We have developed a website that we hope will facilitate student-driven inquiry beyond the classroom and foster inter-institutional collaboration in this endeavor. We conclude the paper with a discussion of the potential limitations of the course and how to evaluate the success of the course and the website.


The observation of the local ordering characteristics of spermidine-condensed DNA: atomic force microscopy and polarizing microscopy studies.
Condensation of DNA by multivalent cations can provide useful insights into the physical factors governing the folding and packaging of DNA in vivo. In this work, local ordered structures of spermidine-DNA complexes prepared from different DNA concentrations have been examined by using atomic force microscopy (AFM) and polarizing microscopy (PM). Two types (I and II) of DNA condensates, significantly different in sizes, were observed. It was found that for extremely dilute solutions (DNA concentrations around 1 ng/microl or below), the DNA molecules would collapse into toroidal structures with a volume equivalent to a single lambda-DNA (type I). In relatively dilute solutions (DNA concentrations between 1 and 10 ng/microll), a significantly larger structure of multimolecular toroids (circular and elliptical, type II) were formed, which were constructed by many fine particles. Measurements show that the average diameter of these fine particles was similar to the outer diameter of the monomolecular toroids observed in extremely dilute solutions, and the thickness of the multimolecular toroids had a distribution of multi-layers with height increments of 11 nm, indicating that the multimolecular toroidal structures have lamellar characteristics. Moreover, by enriching the DNA-spermidine complexes in very diluted solution, branch-like structures constructed by subunits were observed by using AFM. The analysis of the pellets in polarizing microscopy reveals a liquid-crystal-like pattern. These observations suggest that DNA-spermidine condensation could have multiple stages, which are very sensitive to the DNA and spermidine concentrations.


Orthodontic treatment for prominent lower front teeth (Class III malocclusion) in children.
Prominent lower front teeth (termed reverse bite; under bite; Class III malocclusion) may be due to a combination of the jaw or tooth positions or both. The upper jaw (maxilla) can be too far back or the lower jaw (mandible) too far forward, or both. Prominent lower front teeth can also occur if the upper front teeth (incisors) are tipped back or the lower front teeth are tipped forwards, or both. Various treatment approaches have been described to correct prominent lower front teeth in children and adolescents. To assess the effects of orthodontic treatment for prominent lower front teeth in children and adolescents. We searched the following databases: Cochrane Oral Health Group's Trials Register (to 7 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE via OVID (1946 to 7 January 2013), and EMBASE via OVID (1980 to 7 January 2013). Randomised controlled trials (RCTs) recruiting children or adolescents or both (aged 16 years or less) receiving any type of orthodontic treatment to correct prominent lower front teeth (Class III malocclusion). Orthodontic treatments were compared with control groups who received either no treatment, delayed treatment or a different active intervention. Screening of references, identification of included and excluded studies, data extraction and assessment of the risk of bias of the included studies was performed independently and in duplicate by two review authors. The mean differences with 95% confidence intervals were calculated for continuous data. Meta-analysis was only undertaken when studies of similar comparisons reported comparable outcome measures. A fixed-effect model was used. The I2 statistic was used as a measure of statistical heterogeneity. Seven RCTs with a total of 339 participants were included in this review. One study was assessed as at low risk of bias, three studies were at high risk of bias, and in the remaining three studies risk of bias was unclear. Four studies reported on the use of a facemask, two on the chin cup, one on the tandem traction bow appliance, and one on mandibular headgear. One study reported on both the chin cup and mandibular headgear appliances.One study (n = 73, low quality evidence), comparing a facemask to no treatment, reported a mean difference (MD) in overjet of 4.10 mm (95% confidence interval (CI) 3.04 to 5.16; P value < 0.0001) favouring the facemask treatment. Two studies comparing facemasks to untreated control did not report the outcome of overjet. Three studies (n = 155, low quality evidence) reported ANB (an angular measurement relating the positions of the top and bottom jaws) differences immediately after treatment with a facemask when compared to an untreated control. The pooled data showed a statistically significant MD in ANB in favour of the facemask of 3.93 ° (95% CI 3.46 to 4.39; P value < 0.0001). There was significant heterogeneity between these studies (I2 = 82%). This is likely to have been caused by the different populations studied and the different ages at the time of treatment.One study (n = 73, low quality evidence) reported outcomes of the use of the facemask compared to an untreated control at three years follow-up. This study showed that improvements in overjet and ANB were still present three years post-treatment. In this study, adverse effects were reported but due to the low prevalence of temporomandibular (TMJ) signs and symptoms no analysis was undertaken.Two studies (n = 90, low quality evidence) compared the chin cup with an untreated control. Both studies found a statistically significant improvement in ANB, and one study also found an improvement in the Wits appraisal. Data from these two studies were not suitable for pooling.A single study of the tandem traction bow appliance compared to untreated control (n = 30, very low quality evidence) showed a statistically significant difference in both overjet and ANB favouring the intervention group.The remaining two studies did not report the primary outcome of this review. There is some evidence that the use of a facemask to correct prominent lower front teeth in children is effective when compared to no treatment on a short-term basis. However, in view of the general poor quality of the included studies, these results should be viewed with caution. Further randomised controlled trials with long follow-up are required.


Data-driven encoding for quantitative genetic trait prediction.
Given a set of biallelic molecular markers, such as SNPs, with genotype values on a collection of plant, animal or human samples, the goal of quantitative genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Quantitative genetic trait prediction is usually represented as linear regression models which require quantitative encodings for the genotypes: the three distinct genotype values, corresponding to one heterozygous and two homozygous alleles, are usually coded as integers, and manipulated algebraically in the model. Further, epistasis between multiple markers is modeled as multiplication between the markers: it is unclear that the regression model continues to be effective under this. In this work we investigate the effects of encodings to the quantitative genetic trait prediction problem. We first showed that different encodings lead to different prediction accuracies, in many test cases. We then proposed a data-driven encoding strategy, where we encode the genotypes according to their distribution in the phenotypes and we allow each marker to have different encodings. We show in our experiments that this encoding strategy is able to improve the performance of the genetic trait prediction method and it is more helpful for the oligogenic traits, whose values rely on a relatively small set of markers. To the best of our knowledge, this is the first paper that discusses the effects of encodings to the genetic trait prediction problem.


Dose-dependent pharmacokinetics of enprofylline and its renal handling in rats.
The effect of dosage on the pharmacokinetics of the potent bronchodilator enprofylline (3-propylxanthine; PX) and its renal handling were investigated in rats. Enprofylline (PX) was administered iv in dosages of 2.5, 10, 20, and 40 mg/kg, and PX concentration in plasma and urine was determined by HPLC. The pharmacokinetic parameters were estimated by model-independent methods. The disappearance of PX from plasma was delayed as dosage was increased. The corresponding pharmacokinetic parameters also showed dose dependency; increases in the volume of distribution (Vd) and mean residence time (MRT) and a decrease in total body clearance (CLT) were observed as dosage was increased from 2.5 to 40 mg/kg. Approximately 80% of the dose, however, was excreted in urine as unchanged PX. Plasma protein binding studies of PX showed concentration dependency and allowed determination of binding parameters, with an apparent dissociation constant (Kd) of 162.50 microM and a binding capacity (nP) of 565.23 microM. Some pharmacokinetic parameters for unbound PX calculated by total plasma concentration and binding parameters also showed dose-dependent characteristics. However, no significant change in Vd for unbound PX was observed among administered doses, indicating that the distribution of PX into the body tissues is not changed by an increase in dosage. Renal clearance of unbound PX significantly increased as plasma concentration decreased. The maximum transport capacity (Vmax) and the Michaelis-Menten constant (Km) for tubular secretion were 60.53 micrograms/min and 2.27 micrograms/mL, respectively. The aim of the present study is to demonstrate that both saturable tubular secretion and concentration-dependent protein binding are responsible for the dose-dependent pharmacokinetics of PX in rats.


A low-cost concurrent TSV test architecture with lossless test output compression scheme.
As the traditional IC design migrates to three-dimensional integrated circuits (3D-ICs) design, new challenges need to be considered carefully to solve its reliability and yield issues. 3D-ICs using through-silicon-vias (TSVs) can have latent defects such as resistive open and bridge defects, which are caused by the thermal stress during the fabrication process. These latent defects lead to the deterioration of the electrical performance of TSVs caused by an undesired increase in the resistance-capacitance (RC) delay. For this reason, various post-bond test methodologies have been studied to improve the reliability of 3D-ICs. Cost reduction in these TSV test architectures is also currently being studied by decreasing various factors such as hardware overhead, test time, and the peak current consumption. Usually, a single test-clock-period is required to determine whether the test result contains the defective TSV. When the test result of any TSVs fails, we use another single test-clock-period to classify its defect type. In this paper, we propose a new TSV test architecture to transfer the combined test output of the test result and the specific defect type to the pad during the single test-clock-period. Our proposed test architecture also provides a reliable block-based concurrent testing to optimize the test time by dividing the die into concurrent blocks. The experimental results showed that our proposed test architecture could reduce the test time and the hardware overhead substantially by ensuring that the reasonable peak power consumption for mass production was reasonable without the test quality being adversely affected.