Robust Visual Tracking via Convolutional Networks Without Training.
Deep networks have been successfully applied to visual tracking by learning a generic representation offline from numerous training images. However, the offline training is time-consuming and the learned generic representation may be less discriminative for tracking specific objects. In this paper, we present that, even without offline training with a large amount of auxiliary data, simple two-layer convolutional networks can be powerful enough to learn robust representations for visual tracking. In the first frame, we extract a set of normalized patches from the target region as fixed filters, which integrate a series of adaptive contextual filters surrounding the target to define a set of feature maps in the subsequent frames. These maps measure similarities between each filter and useful local intensity patterns across the target, thereby encoding its local structural information. Furthermore, all the maps together form a global representation, via which the inner geometric layout of the target is also preserved. A simple soft shrinkage method that suppresses noisy values below an adaptive threshold is employed to de-noise the global representation. Our convolutional networks have a lightweight structure and perform favorably against several state-of-the-art methods on the recent tracking benchmark data set with 50 challenging videos.


The secretion of an intrinsically disordered protein with different secretion signals in Bacillus subtilis.
In this study, a naturally unsecretory intrinsically disordered domain of nucleoskeletal-like protein (Nsp) was attempted to be secreted with different types of secretion signals in Bacillus subtilis. The results showed that Nsp can be secreted efficiently by all selected Sec-type signal peptides. Nsp was successfully exported when fused to Tat-type signal peptides but less efficient than Sec-type. The fusion protein with the non-classical extracellular proteins can be detected in the cell and extracellular milieu. This study further demonstrated that the mature protein plays an important role in protein secretion. Moreover, these results indicated that Nsp could be a useful tool to understand the individual roles of mature proteins and signal peptide in protein secretion, to evaluate the effect of conformation of mature proteins on their export pathway when coupled with Tat-type signal peptide, and to seek the signal of non-classical secretory proteins.


Some assembly required: dedicated chaperones in eukaryotic proteasome biogenesis.
The 26S proteasome is the key eukaryotic protease responsible for the degradation of intracellular proteins. Protein degradation by the 26S proteasome plays important roles in numerous cellular processes, including the cell cycle, differentiation, apoptosis, and the removal of damaged or misfolded proteins. How this 2.5-MDa complex, composed of at least 32 different polypeptides, is assembled in the first place is not well understood. However, it has become evident that this complicated task is facilitated by a framework of protein factors that chaperone the nascent proteasome through its various stages of assembly. We review here the known proteasome-specific assembly factors, most only recently discovered, and describe their potential roles in proteasome assembly, with an emphasis on the many remaining unanswered questions about this intricate process of assisted self-assembly.


Prevalence of Toxocara eggs in Latin American parks: a systematic review and meta-analysis.
Toxocariasis is an infection caused in canines, felines, humans, and other vertebrates by species of the genus Toxocara, such as T. canis and T. cati. The embryonated eggs of these parasites are the main form of acquisition of the infection both for definitive hosts, such as the dog and the cat, respectively and for paratenic hosts, such as humans and other vertebrates. Toxocariasis infection in humans causes visceral larva migrans syndrome. When deposited on park soils, environmental contamination becomes a risk for environmental, human, and animal health. To systemically estimate the prevalence of Toxocara spp. eggs in park soils in Latin America. A systematic review and meta-analysis were performed to evaluate the prevalence of Toxocara eggs in park soils in Latin America, defined by copro-parasitological, molecular and immunological techniques. We searched PubMed, Scopus, Web of Sciences, Embase, LILACS and SciELO for studies published from 1900 through 28 January 2023. A meta-analysis was performed using a random-effects model to calculate the pooled prevalence and 95% confidence intervals (95% CI). Heterogeneity was measured through I2 statistics. Forty-nine studies (2,508 parks and 12,833 samples) were included, of whom 44 had a low risk of bias. The pooled prevalence of Toxocara eggs in parks in Latin America was 50.0% (95% CI: 40.0%-60.0%). Argentina had the highest prevalence of Toxocara eggs in parks (100%), followed by Brazil (66%) and Venezuela (63%). The pooled prevalence of Toxocara eggs in soil samples was 20.0% (95% CI: 14.0%-26.0%); in faecal samples, it was 13.0% (95% CI: 6.0%-23.0%). The presence of Toxocara canis eggs in public parks in Latin America is a zoonotic and public health threat for the people who go to these places, especially if children play on the ground with dirt or contaminated objects; since many pet owners and general public are not adequately informed about the mode of transmission of this parasite.


Endovascular treatment of stenoses in the superior vena cava syndrome caused by non-tumoral lesions.
We report our experience in percutaneous treatment of non-tumoral superior vena cava syndrome (SVCS) between December 1998 and July 2001. During a period of 2.5 years, 9 patients (age range 27-84 years, mean age 50 years) were treated percutaneously for significant non-tumoral SVCS. Symptomatic SVCS were due to dialysis catheters (7), central line (1) and radiation therapy (1). In thrombotic occlusions and severe stenosis, a preliminary in situ thrombolysis was achieved before angioplasty. Patients were followed by echo-Doppler, computed tomography angiography (CTA), magnetic resonance angiography (MRA), or phlebography. Complete recanalization of the veins and immediate resolution of symptomatic SVCS were obtained in all patients, with no procedure-related complication. Thirteen stents were placed in 9 patients with a mean clinical follow-up of 9.1 months (range 2-23 months). One hundred percent patency at 6 months was obtained. Two patients recurred twice and were treated with new stent placement. At 12 months the patency was 67% and assisted patency was 100%. Stent placement in benign symptomatic SVCS is a safe and minimally invasive procedure, with no technical and clinical complications in our experience. It allowed immediate relief of symptoms, and in dialysed patients could provide continued use of hemodialysis access. Close clinical surveillance is mandatory to assess stent patency.


[Relaparotomy: clinical, strategic and organizational aspects].
The results of relaparotomy (RL) performance in 118 patients were analyzed. Mortality was 16.1%. In 50.8% of patients RL was done with delay. There were proposed for timely diagnosis of postoperative complications to use the "alarm" symptoms group and during RL performance--to follow definite technical methods and rules. The RL performance necessity in 62.7% patients was caused by surgical technique failures and nonrational method of the first operation choice.


Driving a more effective health care market by putting consumers behind the wheel.
In any other rational market, the consumer drives demand, and the provider responds with products and services aimed at meeting individual needs. This rational market does not exist in today's group health care system. The ramifications are significant: declining consumer and provider satisfaction, out-of-control costs, a rising uninsured population, and growing employer burdens. Turning this chaotic world around requires a more active and informed consumer. Transformation is under way with solutions like Sageo, a new e-business from Hewitt Associates that is revolutionizing the way health care benefits are offered, selected, and administered. For companies that offer Sageo's services, their employees and retirees gain direct access to health care coverage and content, enabling them to research, select, and enroll in the appropriate package based on their individual needs.


A fatal case of Ecthyma Gangrenosum in a critically ill and immunocompromised patient.
This brief picture-oriented case report focuses on typical skin lesions in a patient who developed Ecthyma gangrenosum and pseudomonal sepsis after extensive immunosuppressive therapy for Pemphigus vulgaris. The patient was immunosuppressed with high doses of glucocorticoids and azathioprine; the follow-up after the treatment was not carried out well due to the pandemic conditions and because the patient herself got a Covid infection, which resulted in the development of pseudomonal sepsis and Ecthyma gangrenosum. The outcome was fatal despite extensive broad-spectrum antibiotic therapy, plasmapheresis, and intravenous immunoglobulins. Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients, because of multi-drug resistance in the first place.


Loss of alpha 1 connexin does not alter the prenatal differentiation of pancreatic beta cells and leads to the identification of another islet cell connexin.
Connexin alpha 1, also referred to as Cx43, has thus far been the only gap junction protein identified between the hormone-producing cells of pancreatic islets. To investigate whether loss of this connexin affects the development of endocrine pancreas and the differentiation of insulin-producing beta cells, we have taken advantage of a transgenic line in which the gene coding for connexin alpha 1 had been functionally deleted by homologous recombination. Analysis of pancreas at embryonal day 19.5 (E 19.5) after immunostaining for the four main types of islet hormones, showed that islet cell development was similar in homozygous transgenic mice that completely lacked alpha 1 connexin, in mice that were heterozygous for the transgene, and in age-matched controls with a genetic background similar to that of the transgenic animals. In particular, the three animal groups featured beta cells that had a similar insulin content and ultrastructural organization, including the presence of typical gap junction plaques on the membrane. However, quantitative analysis of freeze-fractured membranes showed that these plaques were less frequent in the transgenic mice lacking alpha 1 connexin. This finding prompted us to revisit the connexin pattern of normal pancreatic beta cells. Using RT-PCR amplification and primers specific for nine of the mammalian connexins, we have found that normal rat and mouse pancreas contain six connexin transcripts, including one that codes for alpha 6 connexin, a protein also referred to as Cx45. This transcript was also identified in isolated pancreatic islets, in FACS-purified suspensions of primary beta cells and in the insulin-producing cells of an experimental tumor. Using antibodies, we found that connexin alpha 6 is expressed by the latter cells, as well as by pancreatic fibroblasts and epithelial duct cells. The data show that pancreatic islets have a normal prenatal development in mice that no longer express alpha 1 connexin. They further provide evidence that normal and tumoral insulin-producing cells natively coexpress connexins alpha 1 and alpha 6.


[The role of lead as a harmful factor in the manufacture of crystal products].
The article deals with research into dust contamination of crystal processing shops, and contains toxicological data related to different lead-containing dusts. It was established that the dust concentrations containing 51 to 66% silicon dioxide was higher in the crystal-cutting shops as compared with other shops. The content of lead in the dust in the composition and crystal processing shops was higher than that in the crystal-cutting shops. Toxicological express-analysis of different dusts performed on cell-cultures revealed that processing-induced crystal dusts were not as toxic as red lead (lead oxide) dusts.


Baiheqingjin formula reduces inflammation in mice with asthma by inhibiting the PI3K/AKT/NF-κb signaling pathway.
Baiheqingjin Decoction (BHQJ), which consists of 7 traditional Chinese herbs including Baibu (Stemona tuberosa Lour.), Hezi (Terminalia chebula Retz.), Mahuang (Ephedra sinica Stapf.), Ziwan (Aster tataricus L. f.), Dilong (Pheretima), Sangbaipi (Morus alba L.), and Xianhecao (Agrimonia pilosa Ledeb.). BHQJ is commonly used for treating cough asthma, and variant cough-variant asthma as it, is effective in improving asthma symptoms and reducing airway inflammation. To investigate the mechanisms of BHQJ in treating allergic asthma. We collected information about the components and targets of 6 Chinese medicines (excluding Pheretima) from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Additionally, we obtained genes associated with asthma from six disease databases. To create a protein-protein interaction network, we conducted an intersection analysis using differentially expressed genes derived from RNA transcriptome data. Subsequently, we carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To validate the findings from network pharmacology and transcriptomics, we established an allergic asthma mouse model induced by ovalbumin and conducted in vivo experiments. Using network pharmacology and transcriptomics analyses, we identified the pathways including the PI3K/AKT signaling pathway, and NF-κB signaling pathway. Among these, the involvement of the PI3K/AKT/NF-κB signaling pathway in various pathological processes of asthma, such as airway inflammation, smooth muscle contraction, and excessive mucus production, are well-documented. Histopathological examinations indicated that BHQJ had the potential to mitigate inflammatory cell infiltration and the excessive growth of goblet cells in the airways of asthmatic mice, consequently reducing mucus secretion. Results from Western blot demonstrated that BHQJ could inhibit the activation of the PI3K/AKT/NF-κB pathway at the protein levels. Enzyme-linked immunosorbent assay findings revealed that BHQJ could reduce the production of typical "type 2 asthma" cytokines and immunoglobulin (Ig) E in the blood. These discoveries imply that BHQJ has the potential to reduce the release of inflammatory cytokines and suppress the overactivation of the PI3K/AKT/NF-κB signaling pathway, thus offering a therapeutic approach for asthma. Our research offers initial insights into the fundamental mechanisms through which BHQJ treats asthma. This study reveals the potential mechanism of BHQJ in treating asthma, particularly its role in reducing inflammatory cytokines, mucus production, and cell infiltration, as well as inhibiting the expression of PI3K/AKT/P65 phosphorylated protein. These findings indicate the potential of BHQJ in treating asthma. In summary, our study provides preliminary insights into the asthma treatment mechanism of BHQJ and provides guidance for future research.


[The association of intestinal microbiota with obesity].
Intestinal microbiota (IM) plays a role in the development of obesity and its associated low grade inflammation. Bacterial colonization of the gastrointestinal tract of germ free mice (without microbiota) increases by 60% their fat mass, alters their fasting glucose and insulin levels, triples their hepatic triglycerides and induces adipocyte hypertrophy. IM favors fat storage in adipocytes through the inhibition of Fiaf (Fasting Induced Adipocyte Factor), an inhibitor of lipoprotein lipase. Compared with normal weight subjects, the IM from obese exhibits a higher proportion of Firmicutes/Bacteroidetes and is more efficient in extracting energy from foodstuffs. The loss of bodyweight by a hypocaloric diet reverts the proportion of bacteria to that of lean subjects. The intake of a high fat diet also alters the IM, affecting intestinal barrier function and favoring endotoxinemia. These events increase oxidative and pro-inflammatory processes in plasma and peripheral tissues and increment the risk of insulin resistance. Such events are reverted by the administration of prebiotics which stimulate the growth of Bifdobacterium and Lactobacillus species in the colon, reestablishing the gut homeostasis. Interestingly, products resulting from the fermentation of prebiotics stimulate the differentiation of enteroendocrine cells and the release of glucagon like peptide 1 and peptide YY, that have insulin like and anorexigenic activities, thus contributing to body weight equilibrium.


Polarization-dependent plasmonic coupling in dual-layer metallic structures at terahertz frequencies.
Dual-layer metallic wire-hole structures were fabricated and their terahertz transmission properties were measured. They exhibit polarization-dependent transmittance with large extinction ratios. Simulation and experimental results on structures with different wire-to-hole orientations provide strong evidence that the resonance peaks are caused by plasmonic coupling between the two metallic layers. A simplified LC-circuit model is proposed to explain the coupling mechanism and to estimate the peak frequencies. Our results suggest that specific electromagnetic response can be achieved by appropriate design of the geometrical patterns on the two metallic layers and a suitable polarization of the incident wave.


Handgrip Strength: A Population-Based Study of Norms and Age Trajectories for 3- to 17-Year-Olds.
To provide normative values and equations for grip strength obtained from a population-based sample of individuals 3 to 17 years of age. This cross-sectional study used grip strength data from 2706 participants (49.2% males, 91% right-hand dominant) in the normative phase of the National Institutes of Health Toolbox project. Analyses showed greater strength in the dominant hand in boys and with each yearly increase in age. Normative data are presented separately for each side, sex, and age. Separate regression equations using age and weight as explanatory variables of grip strength are provided for each side by sex. The normative data can serve as a guide for interpreting grip strength measurements. The trajectories can be used to investigate the effect of various pathologies and conditions on grip strength during physical maturation.


Pioneering topological methods for network-based drug-target prediction by exploiting a brain-network self-organization theory.
The bipartite network representation of the drug-target interactions (DTIs) in a biosystem enhances understanding of the drugs' multifaceted action modes, suggests therapeutic switching for approved drugs and unveils possible side effects. As experimental testing of DTIs is costly and time-consuming, computational predictors are of great aid. Here, for the first time, state-of-the-art DTI supervised predictors custom-made in network biology were compared-using standard and innovative validation frameworks-with unsupervised pure topological-based models designed for general-purpose link prediction in bipartite networks. Surprisingly, our results show that the bipartite topology alone, if adequately exploited by means of the recently proposed local-community-paradigm (LCP) theory-initially detected in brain-network topological self-organization and afterwards generalized to any complex network-is able to suggest highly reliable predictions, with comparable performance with the state-of-the-art-supervised methods that exploit additional (non-topological, for instance biochemical) DTI knowledge. Furthermore, a detailed analysis of the novel predictions revealed that each class of methods prioritizes distinct true interactions; hence, combining methodologies based on diverse principles represents a promising strategy to improve drug-target discovery. To conclude, this study promotes the power of bio-inspired computing, demonstrating that simple unsupervised rules inspired by principles of topological self-organization and adaptiveness arising during learning in living intelligent systems (like the brain) can efficiently equal perform complicated algorithms based on advanced, supervised and knowledge-based engineering.


Vagal influences in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with therapeutic interventions that include corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. RA exerts a significant socio-economic burden and despite the use of existing treatments some patients end up with disabling symptoms. The autonomic nervous system (ANS) is a brain-body interface that serves to regulate homeostasis by integrating the external environment with the internal milieu. The main neural substrate of the parasympathetic branch of the ANS is the vagus nerve (VN). The discovery of the role of the ANS and the VN in mediating and dampening the inflammatory response has led to the proposal that modulation of neural circuits may serve as a valuable therapeutic tool. Recent studies have explored the role of the VN in this inflammatory reflex and have provided evidence that stimulation may represent a novel new therapeutic intervention. Accumulating evidence suggests that modulation of the parasympathetic tone results in a broad physiological multi-level response, including decreased pro-inflammatory cytokine response in terms of tumour necrosis factor-α, interleukin-1 (IL-1), and IL-6, and may result in an enhanced macrophage switch from M1 to M2 cells and potentially an increased level of the anti-inflammatory cytokine IL-10. Therefore, therapeutic electrical modulation of the VN may serve as an alternative, non-pharmacological, neuroimmunomodulatory intervention in RA in the future. This review gives a focused introduction to the mechanistic link between the ANS and the immune system.


Laser activatable perfluorocarbon bubbles for imaging and therapy through enhanced absorption from coupled silica coated gold nanoparticles.
Nanoparticles have extensively been used for cancer therapy and imaging (i.e., theranostics) using various imaging modalities. Due to their physical and chemical properties (e.g., absorption, fluorescence, and magnetic properties) they have been used for image guided therapy for cancer treatment monitoring. There are various limitations that make many theranostic agents unable to be used for the extended periods of time required for enhancing theranostic capabilities. Some of these are due to inherent characteristics (e.g., change and/or breakdown of structure) present upon continuous irradiation and others are due to environmental (i.e., physiological) conditions that can lead to physical instability (i.e., in terms of size) affecting the amount of particles that can accumulate at the target site and the overall contrast that can be achieved. In this study, perfluorohexane (PFH) nanoemulsions (NEs) were synthesized with silica coated gold nanoparticles (PFH-NEs-scAuNPs) in order to give both stable and enhanced signals for cancer imaging by increasing vaporization of the emulsions into bubbles through the process of optical droplet vaporization (ODV). The resulting perfluorohexane bubbles could be imaged using nonlinear ultrasound (NL US) which significantly increases the signal to noise ratio due to the nonlinear scattering properties of oscillating bubbles. The NL US signals from PFH bubbles were found to be more stable compared to conventional bubbles used for contrast imaging. In addition, the vaporization of PFH NEs into bubbles was shown to cause significant cancer cell death reflecting the theranostic capabilities of the formed PFH bubbles. Since cell death is initiated with laser excitation of PFH-NEs-scAuNPs, these nanoparticles can specifically target cancer cells once they have accumulated at the tumor region. Due to the type of theranostic agent and imaging modality used, the PFH-NEs-scAuNPs can be used to provide higher specificity compared to other agents for locating the tumor region by minimizing tissue specific signals while at the same time being used to treat cancer.


An electrical characterisation methodology for identifying the switching mechanism in TiO2 memristive stacks.
Resistive random access memories (RRAMs) can be programmed to discrete resistive levels on demand via voltage pulses with appropriate amplitude and widths. This tuneability enables the design of various emerging concepts, to name a few: neuromorphic applications and reconfigurable circuits. Despite the wide interest in RRAM technologies there is still room for improvement and the key lies with understanding better the underpinning mechanism responsible for resistive switching. This work presents a methodology that aids such efforts, by revealing the nature of the resistive switching through assessing the transport properties in the non-switching operation regimes, before and after switching occurs. Variation in the transport properties obtained by analysing the current-voltage characteristics at distinct temperatures provides experimental evidence for understanding the nature of the responsible mechanism. This study is performed on prototyped device stacks that possess common Au bottom electrodes, identical TiO2 active layers while employing three different top electrodes, Au, Ni and Pt. Our results support in all cases an interface controlled transport due to Schottky emission and suggest that the acquired gradual switching originates by the bias induced modification of the interfacial barrier. Throughout this study, the top electrode material was found to play a role in determining the electroforming requirements and thus indirectly the devices' memristive characteristics whilst both the top and bottom metal/oxide interfaces are found to be modified as result of this process.


Unmet health care needs among CSHCN with neurologic conditions.
Children with neurologic conditions require a variety of services. With this study we examined health care needs and unmet needs among children with neurologic conditions. Cross-sectional data reported by parents of 3- to 17-year-olds in the 2005-2006 National Survey of Children With Special Health Care Needs were analyzed. Demographic characteristics, health care needs, and unmet needs of children with special health care needs (CSHCN) and neurologic conditions were descriptively compared with an independent referent group of children without special health care needs; statistical contrasts were performed as a function of the type (conditions included in the Diagnostic and Statistical Manual of Mental Disorders [DSM] or not) and number of reported neurologic conditions. Compared with the parents of children without special health care needs, parents of CSHCN with neurologic conditions were more likely to report unmet health care needs for their child. After adjustment for demographic factors and severity of functional limitation, CSHCN with at least 2 conditions had more visits to a health care provider, needed more services, and reported more unmet needs than CSHCN with a single DSM condition. The magnitude of need among CSHCN was greatest among those with at least 1 of each type of neurologic condition. Unmet health care needs exist among CSHCN with neurologic conditions and are particularly pronounced among children with a combination of both DSM and non-DSM disorders. The health care needs among CSHCN with multiple neurologic conditions may be better served by targeted efforts to improve care coordination.


A pH-mucosa area unit of measure to consider morphology of the oesophagus when evaluating oesophagitis.
Gastro-oesophageal pH measurements are routinely carried out to quantify and determine if levels of acid reflux are responsible for symptoms. Although considered the 'gold standard', evidence suggests that pH measurements do not correlate well with the degree of oesophagitis seen during endoscopy. In this study the current measure of pH was critically examined taking into account both the effects of changes in luminal diameter and endoscopy observations. The oesophageal lumen diameter was investigated using a barium swallow for 25 patients presenting with oesophageal disorders. For each subject the widest luminal diameter was measured for a series of five controlled swallows. The results showed that the lumen diameter varied widely from 0.9 to 3.8 cm. An alternative approach to the current measurement of pH was explored. In this approach the exposure not only included the luminal pH and time exposed but also the area of mucosa exposed as a result of differing luminal diameters. Although it is currently not possible to assess the diameter or morphology of the oesophageal lumen during a pH study, the analysis highlighted that the current measure of pH exposure time does not include the area of mucosa exposed. These results may explain, to some extent, the poor correlation between pH measurements and degree of oesophagitis seen during endoscopy.


New Approach for Risk Estimation Algorithms of BRCA1/2 Negativeness Detection with Modelling Supervised Machine Learning Techniques.
BRCA1/2 gene testing is a difficult, expensive, and time-consuming test which requires excessive work load. The identification of the BRCA1/2 gene mutations is significantly important in the selection of treatment and the risk of secondary cancer. We aimed to develop an algorithm considering all the clinical, demographic, and genetic features of patients for identifying the BRCA1/2 negativity in the present study. An experimental dataset was created with the collection of the all clinical, demographic, and genetic features of breast cancer patients for 20 years. This dataset consisted of 125 features of 2070 high-risk breast cancer patients. All data were numeralized and normalized for detection of the BRCA1/2 negativity in the machine learning algorithm. The performance of the algorithm was identified by studying the machine learning model with the test data. k nearest neighbours (KNN) and decision tree (DT) accuracy rates of 9 features involving Dataset 2 were found to be the most effective. The removal of the unnecessary data in the dataset by reducing the number of features was shown to increase the accuracy rate of algorithm compared with the DT. BRCA1/2 negativity was identified without performing the BRCA1/2 gene test with 92.88% accuracy within minutes in high-risk breast cancer patients with this algorithm, and the test associated result waiting stress, time, and money loss were prevented. That algorithm is suggested be useful in fast performing of the treatment plans of patients and accurately in addition to speeding up the clinical practice.


Retinopathy of Prematurity Versus Familial Exudative Vitreoretinopathy: Report on Clinical and Angiographic Findings.
Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are classified as distinct diseases; however, emerging genetic research and fluoresce-in angiographic evidence suggest a margin of overlap between the two. PATIENTS AND METHODS This was an institutional review board-approved, retrospective case series. A literature review was performed, and medical records of all pediatric patients who underwent examination under anesthesia and laser for FEVR at the Bascom Palmer Eye Institute Pediatric Retina Service by one of the authors (AMB) from Jan. 1, 2006, to June 30, 2013, were analyzed retrospectively. Nine infants born prematurely had fluorescein angiograms and a clinical course most consistent with FEVR. Angiographic findings included irregular sprouts of vascularization at the vascular/ avascular junction, distinct pruning of vessels, pinpoint areas of hyperfluorescence, and segmental areas of vascular leakage. The authors propose a classification of ROPER (ROP vs. FEVR) to more accurately stratify these patients. Identification of this subset of patients will allow for sustained surveillance of infants with ROPER who demonstrate a continuing risk of disease activity.


Cervical cancer screening among HIV-positive women. Retrospective cohort study from a tertiary care HIV clinic.
OBJECTIVE To determine the rate of cervical screening among HIV-positive women who received care at a tertiary care clinic, and to determine whether screening rates were influenced by having a primary care provider.DESIGN Retrospective chart review.SETTING Tertiary care outpatient clinic in Ottawa, Ont. PARTICIPANTS Women who were HIV-positive receiving care at the Ottawa Hospital General Campus Immuno deficiency Clinic between July 1, 2002, and June 30, 2005.MAIN OUTCOME MEASURES Whether patients had primary care providers and whether they received cervical screening. We recorded information on patient demographics, HIV status, primary care providers, and cervical screening, including date, results, and type of health care provider ordering the screening.RESULTS Fifty-eight percent (126 of 218) of the women had at least 1 cervical screening test during the 3-year period. Thirty-three percent (42 of 126) of the women who underwent cervical screening had at least 1 abnormal test result. The proportion of women who did not have any cervical tests performed was higher among women who did not have primary care providers (8 of 12 [67%] vs 84 of 206 [41%]; relative risk 1.6, 95%confidence interval 1.06 to 2.52, P < .05), although this group was small.CONCLUSION Despite the high proportion of abnormal cervical screening test results among HIV-positive women, screening rates remained low. Our results support our hypothesis that those women who do not have primary care providers are less likely to undergo cervical screening.


Additional microvascular anastomosis in reconstruction after total esophagectomy for cervical esophageal carcinoma.
Maintaining sufficient blood flow to the substitute organ after total esophagectomy is essential for decreasing the risk of anastomotic leakage. Additional venous, or arterial and venous, anastomoses between the vessels of the gastric tube and the vessels in the neck after total esophagectomy are described for 11 patients with cervical esophageal carcinoma. The tissue blood flow was measured by laser Doppler flowmetry before and after anastomosis. Venous anastomosis was performed for all 11 patients, and arterial anastomosis was added for 7 patients. A significant increase in tissue blood flow was observed after venous anastomosis alone (mean, 19%; P < 0.05) and after arterial and venous anastomoses (mean 43%; P < 0.01). There was no anastomotic leakage or hospital death. This procedure may reduce the risk of anastomotic leakage especially in the case of pharyngogastrostomy following total esophagectomy.


Optic disc edema as a possible complication of Imatinib mesylate (Gleevec).
Imatinib is effective for a variety of hematologic and nonhematologic malignancies. Well-known ocular side effects are periorbital edema, epiphora, extraocular muscle palsy, and blepharoconjunctivitis. However, optic disc edema has not been reported as a complication of imatinib mesylate. Herein, we describe a patient with chronic myeloid leukemia (CML) who developed optic disc edema during treatment with imatinib. A 14-year-old Korean girl was referred to ophthalmology for a 3-week history of photopsia in both eyes. She had started taking imatinib daily 2 months previously for CML. At the initial exam, slit lamp showed optic disc edema in both eyes, even though visual acuity was 20/20 and other optic nerve function evaluations were within normal limits. We recommended to the oncologist discontinuation of the imatinib treatment. When the patient was followed for 1 week after stopping imatinib treatment, the frequency of photopsia decreased and the optic disc edema improved. Because a second examination 3 weeks after discontinuation of imatinib revealed much improved optic disc edema, she restarted the imatinib treatment. No ocular side effects have been noted so far. Optic disc edema should be considered one of the complications associated with imatinib. We propose discontinuation of the treatment for a short period when optic disc edema occurs.


[Analysis of a patient population of the neurologic-psychiatric admission department of a central prison hospital].
This article represents an attempt to analyse the multivarious and problematic groups of neurological and psychiatric inpatients admitted to a central hospital for prisoners in Baden-Württemberg. This special ward for such patients is unique in its character in the entire Federal Republic of Germany. Patients are differentiated according to diagnosis, length of stay, duration of imprisonment, reason for referral, number of patients referred, and kind of treatment. The four most strongly represented groups of diagnosis consist of the patients with psychogenic reactions, drug addiction, endogenous psychoses and psychopathies. These differ from one another according to treatment regimen, reasons for referral, and mode of hospitalisation. Statistics are given reflecting the problems of non-German, mentally abnormal prisoners and of their suicidal or para-suicidal actions.


Pulsatile lavage for pressure ulcer management in spinal cord injury: a retrospective clinical safety review.
Pressure ulcers are major complications of reduced mobility and/or sensation. Pulsatile lavage therapy delivers localized hydrotherapy directly to the wound utilizing a pulsatile pressurized stream of normal saline. The purpose of this study was to evaluate the clinical safety of pulsatile lavage therapy, provided daily at the bedside, in routine management of Stage III and Stage IV pressure ulcers. Charts from 28 male patients with Stage III and Stage IV pressure ulcers and spinal cord injury (SCI) or spinal cord disorders (SCD) were retrospectively reviewed for documentation of adverse events/safety concerns. Mean therapy duration was 46 days (SD 37 days, range 6-152 days). Treatment was interrupted for 6 days in one patient due to minor wound bleeding. No other adverse events, including backsplash injuries, were documented. The results of this chart review suggest pulsatile lavage therapy can be administered at the patient's bedside without adverse events if appropriate protocols are followed. Additional research to confirm the efficacy and effectiveness of this treatment modality in a broader subject population is warranted.


The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design.
Merozoite surface protein 1 (MSP1) has been identified as a target antigen for protective immune responses against asexual blood stage malaria, but effective vaccines based on MSP1 have not been developed so far. We have modified the sequence of Plasmodium yoelii MSP119 (the C-terminal region of the molecule) and examined the ability of the variant proteins to bind protective monoclonal antibodies and to induce protection by immunization. In parallel, we examined the structure of the protein and the consequences of the amino acid changes. Naturally occurring sequence polymorphisms reduced the binding of individual protective antibodies, indicating that they contribute to immune evasion, but immunization with these variant proteins still provided protective immunity. One variant that resulted in the localized distortion of a loop close to the N-terminus of MSP119 almost completely ablated protection by immunization, indicating the importance of this region of MSP119 as a target for protective immunity and in vaccine development.


A comparative proteomic study to characterize the vinblastine resistance in human ovarian cancer cells.
Drug resistance is a major impediment to the successful treatment of human cancers, including ovarian cancer. Vinblastine (VLB), an antimicrotubule agent, is one of the chemotherapeutic drugs that exhibit resistance in ovarian cancer patients. To determine the protein factors that are involved in vinblastine resistance in human ovarian cancer cells, a combination of sample pre-fractionation and high-resolution 2-DE proteomic analysis was performed. Approximately 1200 proteins were detected and quantitatively compared in both nuclear/membrane and cytosolic fractions. Sixty-nine proteins from the nuclear/membrane fraction showed altered expression levels, whereas 59 were altered in the cytosolic fraction between SKOV3 (vinblastine-sensitive) and SKVLB (vinblastine-resistant) cell lines. These proteins include membrane-associated, chromatin remodeling, cytoskeletal, and microtubule-associated proteins as well as others that regulate signal transduction. This study not only demonstrates a novel understanding of the mechanism of drug resistance but also provides a valuable resource for future studies on drug resistance to vinblastine. In addition, it also represents a good example of how to increase the protein dynamic range and reduce sample complexity using currently available tools.


Recent advances in the therapeutic perspectives of Nutlin-3.
Nutlin-3 is a small molecule inhibitor of the MDM2/p53 interaction, which leads to the non-genotoxic p53 stabilization, activation of cell cycle arrest and apoptosis pathways. A series of recent studies have strengthened the concept that selective, non-genotoxic p53 activation by Nutlin-3 might represent an alternative to the current cytotoxic chemotherapy, in particular for pediatric tumors and for hematological malignancies, which retain a high percentage of p53(wild-type) status at diagnosis. Like most other drugs employed in cancer therapy, it will be unlikely that Nutlin-3 will be used as a monotherapy. In this respect, Nutlin-3 shows a synergistic cytotoxic effect when used in combination with innovative drugs, such as TRAIL or bortozemib. Although Nutlin-3 is currently in phase I clinical trial for the treatment of retinoblastoma, its effects on normal tissues and cell types remain largely to be determined and will require further investigation in the future years.


Mechanism of potassium adaptation.
After chronic dietary potassium loading, epithelia in distal portions of the nephron and large intestine adapt to increase the rate of potassium secretion. This response to increased excretory loads of potassium maintains overall external balance and protects against the potentially lethal effects of hyperkalemia. The cellular adaptation in epithelia involved in preserving potassium homeostasis during potassium loading is characterized by an increase in the number of potassium pumps, reflected by an increase in Na-K-ATPase activity, in the basolateral cell membrane due, at least in part, to an amplification in the area of this membrane, and by an increase in transepithelial potential difference in most, but not all, adapted epithelia. These changes suggest that potassium adaptation is due to a step-up in the rate of cell uptake of potassium. In addition to chronic dietary loading, other conditions such as chronic renal insufficiency, elevated levels of mineralocorticoids, and administration of glucocorticoids are also characterized by accelerated rates of potassium secretion in the distal nephron and colonic mucosa and stimulation of Na-K-ATPase in basolateral portions of the cell membrane. These cellular changes in epithelia with increased capacity for potassium secretion are discussed in the context of our present understanding of mechanisms that control potassium excretion in urine and feces.


Barriers to the uptake of eye health services of the children in rural Bangladesh: A community-based cross-sectional survey.
Globally, ocular morbidity and disability among children are major public health concerns. This study was designed to explore the health-seeking behaviours of parents in Bangladesh whose children have ocular problems. A cross-sectional mixed method was followed for this study. The method was designed to measure the eye health care-seeking practices of caregivers/parents with children with ocular morbidity in three unions (the lowest administrative geographical area comprising 30,000-50,000 population) of the Raiganj Upazila under the Sirajganj District of Bangladesh. The study period was from January to April 2017. Face-to-face interviews using a semi-structured quantitative questionnaire with the caregivers and KI were conducted among the health service providers during the study period. This was the first community-based study conducted in Bangladesh to find out caregivers' health-seeking behaviour with identified ocular morbidity. Among 198 confirmed cases of childhood ocular problems, only 87 (43.9%) parents sought health care for their children's ocular morbidities. Better health-seeking behavior was found among the wealthier families. Proportions were 55.3% and 36% among wealthy and low-income families, respectively. Affluent families sought care from qualified service providers. Educated household heads chose qualified service providers for their children at a higher rate than illiterate household heads. Lack of knowledge, lack of awareness and financial constraints are significant barriers to seeking proper health care. More than half of the caregivers did not seek any eye care services for their children. Socio-demographic factors, and financial constraints play an essential role in the health-seeking behaviour of the parents.


Longitudinal Association Between Endothelial Dysfunction, Inflammation, and Clotting Biomarkers With Subclinical Atherosclerosis in Type 1 Diabetes: An Evaluation of the DCCT/EDIC Cohort.
There is considerable interest in identifying biomarkers that predict high risk for the development of macrovascular complications in patients with diabetes. Therefore, the longitudinal association between subclinical atherosclerosis as measured by internal carotid artery intima-media thickness (IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion molecules was examined. Biomarkers were measured at four time points over 20 years in 886 DCCT/EDIC participants with type 1 diabetes. Four composite scores were created by combining z scores generated from within the data set of individual biomarkers: acute-phase reactants (fibrinogen, C-reactive protein), thrombosis (fibrinogen, active and total plasminogen activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction (soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC years 1, 6, and 12, with elevated IMT defined at each time point as being in the upper quintile of its distribution. Logistic regression models indicate that while individual biomarkers were not predictive of or associated with subclinical atherosclerosis, composite scores of acute-phase reactants (odds ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45, 5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our final time point EDIC years 8-11 were associated with higher levels of atherosclerosis at EDIC year 12, but findings were not consistent at early time points. The endothelial dysfunction score was not appreciably predictive of or associated with subclinical atherosclerosis at any of the time points measured. The pathophysiologic relationship between higher biomarker levels and progression of subclinical atherosclerosis remains unclear.


The Mark Coventry Award: Patellofemoral Arthroplasty Results in Better Range of Movement and Early Patient-reported Outcomes Than TKA.
Controversy exists over the surgical treatment for severe patellofemoral osteoarthritis. We therefore wished to compare the outcome of patellofemoral arthroplasty (PFA) with TKA in a blinded randomized controlled trial. In the first 2 years after surgery: (1) Does the overall gain in quality of life differ between the implants based on the area under the curve of patient-reported outcomes (PROs) versus time? (2) Do patients obtain a better quality of life at specific points in time after PFA than after TKA? (3) Do patients get a better range of movement after PFA than after TKA? (4) Does PFA result in more complications than TKA? Patients were eligible if they had debilitating symptoms and isolated patellofemoral disease. One hundred patients were included from 2007 to 2014 and were randomized to PFA or TKA (blinded for the first year; blinded to patient, therapists, primary care physicians, etc; quasiblinded to assessor). Patients were seen for four clinical followups and completed six sets of questionnaires during the first 2 postoperative years. SF-36 bodily pain was the primary outcome. Other outcomes were range of movement, PROs (SF-36, Oxford Knee Score [OKS], Knee injury and Osteoarthritis Outcome Score [KOOS]) as well as complications and revisions. Four percent (two of 50) of patients died within the first 2 years in the PFA group (none in the TKA group), and 2% (one of 50) became ill and declined further participation after 1 year in the PFA group (none in the TKA group). The mean age at inclusion was 64 years (SD 8.9), and 77% (77 of 100) were women. The area under the curve (AUC) up to 2 years for SF-36 bodily pain of patients undergoing PFA and those undergoing TKA was 9.2 (SD 4.3) and 6.5 (SD 4.5) months, respectively (p = 0.008). The SF-36 physical functioning, KOOS symptoms, and OKS also showed a better AUC up to 2 years for PFA compared with TKA (6.6 [SD 4.8] versus 4.2 [SD 4.3] months, p = 0.028; 5.6 [SD 4.1] versus 2.8 [SD 4.5] months, p = 0.006; 7.5 [SD 2.7] versus 5.0 [SD 3.6] months, p = 0.001; respectively). The SF-36 bodily pain improvement at 6 months for patients undergoing PFA and those undergoing TKA was 38 (SD 24) and 27 (SD 23), respectively (p = 0.041), and at 2 years, the improvement was 39 (SD 24) and 33 (SD 22), respectively (p = 0.199). The KOOS symptoms improvement at 6 months for patients undergoing PFA and those undergoing TKA was 24 (SD 20) and 7 (SD 21), respectively (p < 0.001), and at 2 years, the improvement was 27 (SD 19) and 17 (SD 21), respectively (p = 0.023). Improvements from baseline for KOOS pain, SF-36 physical functioning, and OKS also differed in favor of PFA at 6 months, whereas only KOOS symptoms showed a difference between the groups at 2 years. No PRO dimension showed a difference in favor of TKA. At 4 months, 1 year, and 2 years, the ROM change from baseline for patients undergoing PFA and those undergoing TKA was (-7° [SD 13°] versus -18° [SD 14°], p < 0.001; -4° [SD 15°] versus -11° [SD 12°], p = 0.011; and -3° [SD 12°] versus -10° [SD 12°], p = 0.010). There was no difference in the number of complications. During the first 2 postoperative years, there were two revisions in patients undergoing PFA (one to a new PFA and one to a TKA). Patients undergoing PFA obtain a better overall knee-specific quality of life than patients undergoing TKA throughout the first 2 years after operation for isolated patellofemoral osteoarthritis. At 2 years, only KOOS function differs between patients undergoing PFA and those undergoing TKA, whereas other PRO dimensions do not show a difference between groups. The observations can be explained by patients undergoing PFA recovering faster than patients undergoing TKA and the functional outcome being better for patients undergoing PFA up to 9 months. Patients undergoing PFA regain their preoperative ROM, whereas patients undergoing TKA at 2 years have lost 10° of ROM. We found no differences in complications. Level I, therapeutic study.


Expression of an antisense hla fragment in Staphylococcus aureus reduces alpha-toxin production in vitro and attenuates lethal activity in a murine model.
Isogeneic bacterial strains that differ only in the production of a single microbial factor have been invaluable in studying the pathogenesis of bacterial infections. The targeted, intentional inactivation of a gene encoding a potential virulence determinant generally requires homologous recombination to replace the gene with an inactivated allele. To determine whether the insertion and expression of a fragment of a bacterial gene in an antisense orientation could be used as a rapid alternative to allelic inactivation for producing paired isogeneic isolates, we inverted a 600-bp fragment of the Staphylococcus aureus gene encoding alpha-toxin, hla, behind its native promoter on an Escherichia coli-S. aureus shuttle vector. A transformant of an S. aureus strain carrying the antisense hla fragment produced antisense hla RNA and made 16-fold less alpha-toxin than either its parent or an isogeneic transformant containing vector DNA without hla. Also, intraperitoneal injection of 1.5 x 10(9) CFU of the antisense hla-containing transformant was significantly less lethal in a murine model than that of the parent (1 of 10 versus 7 of 10 mice expired [P < 0.02]) or the transformant without hla (1 of 10 versus 7 of 7 mice expired [P < 0.001]). We conclude that the expression of a fragment of hla in an antisense orientation in S. aureus on a plasmid vector reduces alpha-toxin production and the lethal activity of the strain in a murine model. The antisense strategy for creating isogeneic strains of bacteria may facilitate molecular investigations into the pathogenesis of infection. It also may be useful in creating novel live-attenuated strains of bacteria for use as vaccine candidates.


Central control of thermogenesis in mammals.
Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature in mammals and birds during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system, which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and discusses the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E(2), to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors ascends via second-order thermosensory neurons in the dorsal horn of the spinal cord to activate neurons in the lateral parabrachial nucleus, which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis.


The nature of selection during plant domestication.
Plant domestication is an outstanding example of plant-animal co-evolution and is a far richer model for studying evolution than is generally appreciated. There have been numerous studies to identify genes associated with domestication, and archaeological work has provided a clear understanding of the dynamics of human cultivation practices during the Neolithic period. Together, these have provided a better understanding of the selective pressures that accompany crop domestication, and they demonstrate that a synthesis from the twin vantage points of genetics and archaeology can expand our understanding of the nature of evolutionary selection that accompanies domestication.


n-3 fatty acids and cardiovascular disease.
The results of prospective cohort studies indicate that consuming fish or fish oil containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with decreased cardiovascular death, whereas consumption of the vegetable oil-derived n-3 fatty acid a-linolenic acid is not as effective. Randomized control trials (RCTs) in the context of secondary prevention also indicate that the consumption of EPA plus DHA is protective at doses <1 g/d. The therapeutic effect appears to be due to suppression of fatal arrhythmias rather than stabilization of atherosclerotic plaques. At doses >3 g/d, EPA plus DHA can improve cardiovascular disease risk factors, including decreasing plasma triacylglycerols, blood pressure, platelet aggregation, and inflammation, while improving vascular reactivity. Mainly on the basis of the results of RCTs, the American Heart Association recommends that everyone eat oily fish twice per week and that those with coronary heart disease eat 1 g/d of EPA plus DHA from oily fish or supplements. Directions for future research include (1) RCTs to confirm the initial trials showing that EPA plus DHA decreases cardiovascular death and additional studies to determine whether this effect is due to EPA, DHA, or the combination; the dosage of the effective components; and whether the mechanism of action in humans is prevention of fatal arrhythmias. (2) Clinical studies to determine whether the reduction in cardiovascular disease risk factors is due to EPA, DHA, or the combination and the dosage of the effective components. (3) Clinical studies to determine whether vegetable oil-derived alpha-linolenic acid added to a diet enriched in n-6 fatty acids can effectively substitute for fish oil-derived EPA plus DHA.


Cost-effectiveness of percutaneous closure of a patent foramen ovale compared with medical management in patients with a cryptogenic stroke: from the US payer perspective.
Aims: To evaluate the cost-effectiveness of percutaneous patent foramen ovale (PFO) closure, from a US payer perspective. Lower rates of recurrent ischemic stroke have been documented following percutaneous PFO closure in properly selected patients. Stroke in patients aged <60 years is particularly interesting because this population is typically at peak economic productivity and vulnerable to prolonged disability. Materials and methods: A Markov model comprising six health states (Stable after index stroke, Transient ischemic attack, Post-Transient Ischemic Attack, Clinical ischemic stroke, Post-clinical ischemic stroke, and Death) was constructed to evaluate the cost-effectiveness of PFO closure in combination with medical management versus medical management alone. The base-case model employed a 5-year time-horizon, with transition probabilities, clinical inputs, costs, and utility values ascertained from published and national costing sources. Incremental cost-effectiveness ratio (ICER) was evaluated per US guidelines, utilizing a discount rate of 3.0%. Results: At 5 years, overall costs and quality-adjusted life-years (QALYs) obtained from PFO closure compared with medical management were $16,323 vs $7,670 and 4.18 vs 3.77, respectively. At 5 years, PFO closure achieved an ICER of $21,049, beneficially lower than the conventional threshold of $50,000. PFO closure reached cost-effectiveness at 2.3 years (ICER = $47,145). Applying discount rates of 0% and 6% had a negligible impact on base-case model findings. Furthermore, PFO closure was 95.4% likely to be cost-effective, with a willingness-to-pay (WTP) threshold of $50,000 and a 5-year time horizon. Limitations: From a cost perspective, our economic model employed a US patient sub-population, so cost data may not extrapolate to other non-US stroke populations. Conclusion: Percutaneous PFO closure plus medical management represents a cost-effective approach for lowering the risk of recurrent stroke compared with medical management alone.


Experimental Validation of Fully Quantum Fluctuation Theorems Using Dynamic Bayesian Networks.
Fluctuation theorems are fundamental extensions of the second law of thermodynamics for small systems. Their general validity arbitrarily far from equilibrium makes them invaluable in nonequilibrium physics. So far, experimental studies of quantum fluctuation relations do not account for quantum correlations and quantum coherence, two essential quantum properties. We here apply a novel dynamic Bayesian network approach to experimentally test detailed and integral fully quantum fluctuation theorems for heat exchange between two quantum-correlated thermal spins-1/2 in a nuclear magnetic resonance setup. We concretely verify individual integral fluctuation relations for quantum correlations and quantum coherence, as well as for the sum of all quantum contributions. We further investigate the thermodynamic cost of creating correlations and coherence.


VD education in developing countries. A comparison with developed countries.
No new method of control of the sexually transmitted diseases is imminent. Reliance has to be placed on existing methods including health education. Health education has a double role, being a primary method in its own right, and--of equal or greater importance--being involved in the enforcement of all of the other tried methods. A comparison is made of the situation in countries with a developed or an underdeveloped venereal disease control service, in respect of organization, statistical reporting, the various agencies treating venereal disease, clinic and diagnostic facilities, personnel concerned in venereal disease management, and other aspects. The vicious circle inherent in developing countries is outlined. A lack of awareness of the extent of the problem and the presence of other serious competing diseases lead to a low budget, thence to poor diagnostic and treatment facilities, and to few cases being seen in the official clinics and hospitals. Thus relatively small numbers of cases are reported and there is consequently a continuing lack of awareness of the problem. A method of cutting through such a circle is suggested, and the importance of health education activities during this period is emphasized.


Divalproex sodium for the treatment of conduct disorder: a randomized controlled clinical trial.
New treatments for conduct disorder are sorely needed. We aimed to test the efficacy of divalproex sodium for the treatment of conduct disorder. Seventy-one youths with conduct disorder according to DSM-IV criteria were enrolled in a randomized, controlled, 7-week clinical trial. Subjects were all adolescent males with at least 1 crime conviction. Subjects were randomized into high- and low-dose conditions and were openly managed by a clinical team. Subjects and independent outcome raters were blinded to condition. Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Improvement (CGI-I) ratings, Weinberger Adjustment Inventory ratings, and staff ratings of behavioral privilege were used to assess outcome. Intent-to-treat analyses showed significant associations between assignment to the high-dose condition and ratings on the CGI-S (p =.02) and CGI-I (p =.0008). Self-reported weekly impulse control was significantly better in the high-dose condition (p <.05), and association between improvement in self-restraint and treatment condition was of borderline statistical significance (p <.06). Parallel analyses comparing outcome by blood drug level achieved strengthened the results, as expected. This preliminary study in a most difficult population suggests a role for divalproex sodium in the treatment of conduct disorder. Divalproex sodium improved self-reported impulse control and self-restraint, variables shown to be predictive of criminal recidivism. Studies are needed of longer-term impact and side-effect profiles. This is one of few controlled psychopharmacologic studies of conduct disorder.


Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.
Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.


Veterans Affairs Primary Care Provider Perceptions of Insomnia Treatment.
Insomnia is a widespread issue among United States adults and rates of insomnia among veterans are even higher than the general population. Prior research examining primary care provider (PCP) perspectives on insomnia treatment found that: sleep hygiene and pharmacotherapy are the primary treatments offered; PCPs tend to focus on perceived causes of insomnia rather than the insomnia itself; and neither patients nor providers are satisfied with insomnia treatment options. Although insomnia complaints are typically first reported to primary care providers, little research has focused on perspectives regarding insomnia treatment among PCPs working in the largest integrated health care system in the United States-the Veterans Affairs (VA) health care system. This study was conducted to examine VA PCP perceptions of the availability of insomnia treatments, identify specific strategies offered by PCPs, and examine perceptions regarding the importance of treating insomnia and the role of comorbid conditions. A survey was conducted within the VA health care system. Primary care providers completed surveys electronically. A high percentage of veterans (modal response = 20% to 39%) seen in VA primary care settings report an insomnia complaint to their provider. Almost half of respondents do not consistently document insomnia in the medical record (46% endorsed "sometimes," "rarely," or "never"). PCPs routinely advise sleep hygiene recommendations for insomnia (ie, avoid stimulants before bedtime [84.3%], and keep the bedroom environment quiet and dark and comfortable [68.6%]) and many are uncertain if cognitive behavioral therapy for insomnia is available at their facility (43.1%). Findings point to the need for systems-level changes within health care systems, including the adoption of evidence-based clinical practice standards for insomnia and PCP education about the processes that maintain insomnia. A commentary on this article appears in this issue on page 937.


Eye-head coordination toward auditory and visual targets in humans.
Eye-head coordination during gaze orientation toward auditory targets in total darkness has been examined in human subjects. The findings have been compared, for the same subjects, with those obtained by using visual targets. The use of auditory targets when investigating eye-head coordination has some advantages with respect to the more common use of visual targets: (i) more eccentric target positions can be presented to the subject; (ii) visual feedback is excluded during the execution of gaze displacement; (iii) complex patterns of saccadic responses can be elicited. This last aspect is particularly interesting for examining the coupling between the eyes and the head displacements. The experimental findings indicate that during gaze orientation toward a visual or an auditory target the central nervous system adopts the same strategy of using both the saccadic mechanism and the head motor plant. In spite of a common strategy, qualitative and quantitative parameters of the resulting eye-head coordination are slightly different, depending on the nature of the target. The findings relating to patterns of eye-head coordination seem to indicate a dissociation between the eyes and the head, which receive different motor commands independently generated from the gaze error signal. The experimental findings reported in this paper have been summarized in a model of the gaze control system that makes use of a gaze feedback hypothesis through the central reconstruction of the eye and head positions.


A prospective study of the utility of magnetic resonance imaging in determining candidacy for partial breast irradiation.
Retrospective data have demonstrated that breast magnetic resonance imaging (MRI) may change a patient's eligibility for partial breast irradiation (PBI) by identifying multicentric, multifocal, or contralateral disease. The objective of the current study was to prospectively determine the frequency with which MRI identifies occult disease and to establish clinical factors associated with a higher likelihood of MRI prompting changes in PBI eligibility. At The University of Chicago, women with breast cancer uniformly undergo MRI in addition to mammography and ultrasonography. From June 2009 through May 2011, all patients were screened prospectively in a multidisciplinary conference for PBI eligibility based on standard imaging, and the impact of MRI on PBI eligibility according to National Surgical Adjuvant Breast and Bowel Project protocol B-39/Radiation Therapy Oncology Group protocol 0413 entry criteria was recorded. Univariable analysis was performed using clinical characteristics in both the prospective cohort and in a separate cohort of retrospectively identified patients. Pooled analysis was used to derive a scoring index predictive of the risk that MRI would identify additional disease. A total of 521 patients were screened for PBI eligibility, and 124 (23.8%) patients were deemed eligible for PBI based on standard imaging. MRI findings changed PBI eligibility in 12.9% of patients. In the pooled univariable analysis, tumor size ≥ 2 cm on mammography or ultrasonography (P=.02), age <50 years (P=.01), invasive lobular histology (P=.01), and HER-2/neu amplification (P=.01) were associated with a higher likelihood of MRI changing PBI eligibility. A predictive score was generated by summing the number of significant risk factors. Patients with a score of 0, 1, 2, and 3 had changes to eligibility based on MRI findings in 2.8%, 13.2%, 38.1%, and 100%, respectively (P<.0001). MRI identified additional disease in a significant number of patients eligible for PBI, based on standard imaging. Clinical characteristics may be useful in directing implementation of MRI in the staging of PBI candidates.


Modified effect of urinary cadmium on breast cancer risk by selenium.
Previous experimental studies have shown an antagonistic interaction between cadmium and selenium. We explored the interaction between cadmium and selenium on human breast cancer risk. A case-control study, enrolled 240 incident invasive breast cancer patients and 246 age-matched controls from 2 hospitals, was conducted in Guangzhou, China. Inductively coupled plasma mass spectrometry was used to examine urinary concentrations of cadmium and selenium. Association and interaction of the metal levels with breast cancer risk were tested using generalized additive and logistic regression models. As continuous variables, urinary cadmium [OR (95% CI): 1.16 (1.01-1.34)] but not selenium was significantly linearly associated with breast cancer risk. As tertiles, urinary cadmium did not significantly increase breast cancer risk; whereas women with the second tertile of selenium concentration had a significantly decreased risk of breast cancer as compared with those in the lowest tertile [OR (95% CI): 0.50 (0.30-0.81)]. Among the women with the lowest tertile of selenium, the highest tertile of cadmium significantly increased the risk of breast cancer [OR (95% CI): 2.83 (1.18-6.86)] compared to the lowest tertile of cadmium. A multiplicative interaction was found between tertiles of cadmium and selenium on breast cancer risk (P=0.018), particularly among postmenopausal women. These results suggested that the association of urinary cadmium with breast cancer risk was modified by urinary selenium.


[Uptake of [14C]GABA by rat brain slices; the effect of Ca2+].
The [14C]GABA uptake by slices (0.3 mm thick) of Wistar rat brain cortex was studied for its dependence on the GABA concentration in the medium, time of incubation and the presence of Ca2+. This process is characterized by the absence of saturation; the uptake by slices increases sharply when the concentration of exogenous [14C]GABA reaches 200 microM. Bicucullin (10(-4) M), an antagonist of GABA, inhibits the accumulation of GABA in the concentration of 0.2 microM by 60%, that evidences for a considerable contribution of the receptor binding to this process. The [14C]GABA uptake when Ca2+ is absent in the incubation medium and when its concentration is 10(-3) M is practically the same and comparatively low concentrations of Ca2+ (10(-6)-10(-4] decrease the GABA uptake.


A geographically explicit ecological momentary assessment (GEMA) mixed method for understanding substance use.
Tobacco use is increasingly concentrated within marginalized groups, including LGBTQ+ young adults. Developing tailored interventions to reduce tobacco-related health disparities requires understanding the mechanisms linking individual and contextual factors associated with tobacco use to behavior. This paper presents an in-depth exploration of three cases from a novel mixed method study designed to identify the situational factors and place-based practices of substance use among high-risk individuals. We combined geographically explicit ecological momentary assessment (GEMA) with an adapted travel diary-interview method. Participants (young adult bisexual smokers, ages 18-26) reported on non-smoking and smoking situations for 30 days with a smartphone app. GEMA surveys captured internal and external situational factors (e.g., craving intensity, location type, seeing others smoking). Continuous locational data was collected via smartphone GPS. Subsequently, participants completed in-depth interviews reviewing maps of their own GEMA data. GEMA data and transcripts were analyzed separately and integrated at the case level in a matrix. Using GEMA maps to guide the interview grounded discussion in participants' everyday smoking situations and routines. Interviews clarified participant interpretation of GEMA measures and revealed experiences and meanings of smoking locations and practices. The GEMA method identified the most frequent smoking locations/times for each participant (e.g., afternoons at university). Interviews provided description of associated situational factors and perceptions of smoking contexts (e.g., peer rejection of bisexual identity) and the roles of smoking therein (e.g., physically escape uncomfortable environments). In conclusion, this mixed method contributes to advancing qualitative GIS and other hypothesis-generating approaches working to reveal the richness of individuals' experiences of the everyday contexts of health behavior, while also providing reliable measures of situational predictors of behaviors of interest, such as substance use. Limitations of and future directions for the method are discussed.


Inverse scattering solutions by a sinc basis, multiple source, moment method--Part III: Fast algorithms.
olving the inverse scattering problem for the Helmholtz wave equation without employing the Born or Rytov approximations is a challenging problem, but some slow iterative methods have been proposed. One such method suggested by us is based on solving systems of nonlinear algebraic equations that are derived by applying the method of moments to a sinc basis function expansion of the fields and scattering potential. In the past, we have solved these equations for a 2-D object of n by n pixels in a time proportional to n5. In the present paper, we demonstrate a new method based on FFT convolution and the concept of backprojection which solves these equations in time proportional to n3 X log(n). Several numerical examples are given for images up to 7 by 7 pixels in size. Analogous algorithms to solve the Riccati wave equation in n3 X log(n) time are also suggested, but not verified. A method is suggested for interpolating measurements from one detector geometry to a new perturbed detector geometry whose measurement points fall on a FFT accessible, rectangular grid and thereby render many detector geometrics compatible for use by our fast methods.


Exploring the bioactive potential leaves of Sphaeranthus indicus: Targeting immature stages of Aedes aegypti and Culex quinquefasciatus mosquito vectors through bioassay-guided screening and fraction isolation.
Mosquito control is vital for combating mosquito-borne diseases, but concerns exist regarding the use of synthetic insecticides. This study aimed to explore eco-friendly alternatives derived from natural sources. The larvicidal, pupicidal, and ovicidal activities of various fractions obtained from the hexane leaf extract of Sphaeranthus indicus were investigated against two important mosquito vectors, Aedes aegypti and Culex quinquefasciatus. S. indicus leaves were extracted with hexane and column chromatography was performed with hexane, ethyl acetate, methanol, and their mixtures as eluents. Among the ten fractions (F1-F10) evaluated, fraction 'F-4' exhibited significant activity against third instar larvae, pupae, and eggs of both mosquito species, closely followed by 'F-5' . At a concentration of 10 ppm, 'F-4' achieved 100% mortality in larvae and displayed LC50 values of 5.08 ppm and 5.03 ppm for Ae. aegypti and Cx. quinquefasciatus larvae, respectively. The LC50 values for pupae were 6.12 ppm and 5.83 ppm for Ae. aegypti and Cx. quinquefasciatus, respectively. Regarding ovicidal activity, 'F-4' demonstrated percentages ranging from 63.2% to 64.8% against Ae. aegypti and Cx. quinquefasciatus eggs, respectively. These findings underscore the potent larvicidal, pupicidal, and ovicidal effects of fraction 'F-4' from S. indicus against the targeted mosquito species. Further research is warranted to identify the active compounds responsible for these effects and explore practical applications for sustainable mosquito control strategies.


Psychometric properties of the Chinese version of the Motivation to Change Lifestyle and Health Behaviors for Dementia Risk Reduction scale (MCLHB-DRR) in Chinese community-dwelling older adults.
To assess the psychometric properties of Chinese version of Motivation to Change Lifestyle and Health Behaviors for Dementia Risk Reduction (MCLHB-DRR) scale in Chinese community-dwelling older adults. A convenience sample of 150 Chinese adults aged ≥50 was recruited from local community facilities. Reliability of MCLHB-DRR was evaluated using internal consistency and test-retest reliability over two weeks. Content validity and construct validity were assessed. Translation process followed Brislin's translation model. After excluding two items with poor loadings, the confirmatory factor analysis revealed a good model fit (χ2/df=2.14; CFI=0.91; IFI=0.91; RMSEA=0.087). The scale exhibited good internal consistency (Cronbach's alpha = 0.865), as well as acceptable test-retest reliability (ICC=0.730). The Chinese MCLHB-DRR showed satisfactory psychometric properties, providing valuable insights for promoting dementia risk reduction in Chinese population, considering cultural nuances that shape motivations and knowledge of lifestyle changes.


Coherent Spin Dynamics of Electrons in Two-Dimensional (PEA)2PbI4 Perovskites.
The versatile potential of lead halide perovskites and two-dimensional materials is merged in the Ruddlesden-Popper perovskites having outstanding optical properties. Here, the coherent spin dynamics in Ruddlesden-Popper (PEA)2PbI4 perovskites is investigated by picosecond pump-probe Kerr rotation in an external magnetic field. The Larmor spin precession of resident electrons with a spin dephasing time of 190 ps is identified. The longitudinal spin relaxation time in weak magnetic fields measured by the spin inertia method is as long as 25 μs. A significant anisotropy of the electron g-factor with the in-plane value of +2.45 and out-of-plane value of +2.05 is found. The exciton out-of-plane g-factor of +1.6 is measured by magneto-reflectivity. This work contributes to the understanding of the spin-dependent properties of two-dimensional perovskites and their spin dynamics.


An atypical anatomy of permanent mandibular second molar with five roots.
Especially in molars that may have sometimes aberrant additional root canals, the complexity of tooth internal morphology in individual cases sometimes does not match to admitted classification rules and underlines the risk of missed anatomy during the endodontic management. To our knowledge, a permanent mandibular second molar with independent five roots, three mesial and two distal, each of them harboring a single canal, was not yet reported. Despite the treatment difficulties this tooth could be successfully approached by using dental operative microscope and cone-beam computed tomography (CBCT) with small field of view. Though CBCT is not a routine imagistic examination, in case of atypical tooth anatomy aiming to establish adequate diagnosis and treatment plan, the successful clinical outcome prevails over the irradiation dose.


Production of ethanol by filamentous and yeast-like forms of Mucor indicus from fructose, glucose, sucrose, and molasses.
The fungus Mucor indicus is found in this study able to consume glucose and fructose, but not sucrose in fermentation of sugarcane and sugar beet molasses. This might be an advantage in industries which want to selectively remove glucose and fructose for crystallisation of sucrose present in the molasses. On the other hand, the fungus assimilated sucrose after hydrolysis by the enzyme invertase. The fungus efficiently grew on glucose and fructose and produced ethanol in synthetic media or from molasses. The cultivations were carried out aerobically and anaerobically, and manipulated toward filamentous or yeast-like morphology. Ethanol was the major metabolite in all the experiments. The ethanol yield in anaerobic cultivations was between 0.35 and 0.48 g/g sugars consumed, depending on the carbon source and the growth morphology, while a yield of as low as 0.16 g/g was obtained during aerobic cultivation. The yeast-like form of the fungus showed faster ethanol production with an average productivity of 0.90 g/l h from glucose, fructose and inverted sucrose, than the filamentous form with an average productivity of 0.33 g/l h. The biomass of the fungus was also analyzed with respect to alkali-insoluble material (AIM), chitin, and chitosan. The biomass of the fungus contained per g maximum 0.217 g AIM and 0.042 g chitosan in yeast-like cultivation under aerobic conditions.


Connectome Smoothing via Low-Rank Approximations.
In brain imaging and connectomics, the study of brain networks, estimating the mean of a population of graphs based on a sample is a core problem. Often, this problem is especially difficult because the sample or cohort size is relatively small, sometimes even a single subject, while the number of nodes can be very large with noisy estimates of connectivity. While the element-wise sample mean of the adjacency matrices is a common approach, this method does not exploit the underlying structural properties of the graphs. We propose using a low-rank method that incorporates dimension selection and diagonal augmentation to smooth the estimates and improve performance over the naïve methodology for small sample sizes. Theoretical results for the stochastic block model show that this method offers major improvements when there are many vertices. Similarly, we demonstrate that the low-rank methods outperform the standard sample mean for a variety of independent edge distributions as well as human connectome data derived from the magnetic resonance imaging, especially when the sample sizes are small. Moreover, the low-rank methods yield "eigen-connectomes," which correlate with the lobe-structure of the human brain and superstructures of the mouse brain. These results indicate that the low-rank methods are the important parts of the toolbox for researchers studying populations of graphs in general and statistical connectomics in particular.


Bibliometrics to improve our patients' care!
Bibliometrics is the statistical analysis of scientific publications and trends on a given topic. The use of bibliometric indicators is based on the fact that academic publishing is an essential outcome of research activity, as advancement of science and treatments increases with dissemination of knowledge. Therefore, investigation in our specific field is obligatory, as learning what the current lines of research are can help us to properly orient our research in the coming years. A soon-to-be-published paper analyses 3,027 articles that have appeared in the leading journals of Paediatric Dentistry included in the Journal Citation Reports (JCR): Pediatric Dentistry, the International Journal of Pediatric Dentistry, the European Journal of Paediatric Dentistry and the Journal of Clinical Pediatric Dentistry considering all issues and all articles published from 2008 to 2020. The most frequently addressed topic is surgery (23.4%), which more generally includes pulp treatment, conservative treatments and the use of dental materials (operative dentistry), while the second most discussed topic is prevention (13.2%), followed by oral pathology (10.6%). Subject matters covered less frequently include early childhood caries (ECC) (2.5%) and occlusion (2.7%). In terms of study types, research articles are the most frequently published (74.2%). Among them, the most common study design is observational studies (61.1%), followed by cross-sectional studies (36.9%) and case-control studies (11.9%). With regard to experimental studies, randomised controlled trials (RCTs) are the most common type (11.6%). The number of case series has fallen sharply over time, from 20% 10 years ago to 5% today. Another striking point is that two journals, the International Journal of Pediatric Dentistry and the European Journal of Paediatric Dentistry, have published more than half of the world's output. By looking at the nationality of the authors, it is apparent that research frequently takes place within limited geographical areas, a sign that collaboration between different countries is struggling to take off. Despite the fact that prevention is the second most common topic among the articles analysed in the study-both in absolute terms and also taking into account dental journals focused on different specialties-it still does not play the prominent role it deserves. It is important to emphasise the need for further investigation into the prevention of dental diseases in young patients, as the desired oral health objectives have not yet been achieved. The early identification of risk indicators and the implementation of preventive oral health campaigns aimed at the paediatric population can reduce or prevent the progression of caries, and related expenditures for the replacement of missing teeth at a later age. A final consideration is how interesting it would be to analyse how many of the paediatric medical journals publish papers and articles on paediatric dentistry, as this is in fact another crucial step towards ensuring good oral health for all our young patients!


Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.
Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.


Greenland ice sheet motion insensitive to exceptional meltwater forcing.
Changes to the dynamics of the Greenland ice sheet can be forced by various mechanisms including surface-melt-induced ice acceleration and oceanic forcing of marine-terminating glaciers. We use observations of ice motion to examine the surface melt-induced dynamic response of a land-terminating outlet glacier in southwest Greenland to the exceptional melting observed in 2012. During summer, meltwater generated on the Greenland ice sheet surface accesses the ice sheet bed, lubricating basal motion and resulting in periods of faster ice flow. However, the net impact of varying meltwater volumes upon seasonal and annual ice flow, and thus sea level rise, remains unclear. We show that two extreme melt events (98.6% of the Greenland ice sheet surface experienced melting on July 12, the most significant melt event since 1889, and 79.2% on July 29) and summer ice sheet runoff ~3.9 σ above the 1958-2011 mean resulted in enhanced summer ice motion relative to the average melt year of 2009. However, despite record summer melting, subsequent reduced winter ice motion resulted in 6% less net annual ice motion in 2012 than in 2009. Our findings suggest that surface melt-induced acceleration of land-terminating regions of the ice sheet will remain insignificant even under extreme melting scenarios.


Should silane coupling agents be used when bonding brackets to composite restorations? An in vitro study.
The purpose of this in vitro study was to determine a safe and efficient method for bonding brackets to resin composite (RC), permitting the brackets to tolerate shear forces and allowing removal without causing surface damage to the aesthetic restoration. The shear bond strength (SBS) of 60 brackets bonded to silanated and non-silanated RC surfaces were compared. A Bis-GMA containing orthodontic adhesive system was used to bond stainless steel upper lateral incisor brackets to 60 composite discs, half of which had surface treatment with a silane coupling agent. SBS testing was performed with an Instron universal testing machine. After debond, the bracket base and corresponding RC discs were examined under a stereomicroscope and analyzed using the Adhesive Remnant Index (ARI). Non-parametric tests (Mann-Whitney U) indicated significant differences between the two groups (P < 0.009). Lower bond strengths were found for the silanated group implying that silane agents may be an unnecessary step. However, both groups had a clinically acceptable mean SBS [silanated group = 13.1 megapascals (Mpa), non-silanated group = 19.4 MPa]. Bond failure occurred at the bracket-adhesive interface in both groups. There would appear to be no advantage in using a silane agent when bonding metal orthodontic brackets to filled RCs.


Work stress and satisfaction in relation to personality profiles in a sample of Dutch anaesthesiologists: A questionnaire survey.
Working in anaesthesia is stressful, but also satisfying. Work-related stress can have a negative impact on mental health, whereas work-related satisfaction protects against these harmful effects. How work stress and satisfaction are experienced may be related to personality. Our aim was to study the relationship between personality and perception of work in a sample of Dutch anaesthesiologists. Questionnaire survey. Data were collected in the Netherlands from July 2012 until December 2012. We sent electronic questionnaires to all 1955 practising resident and consultant members of the Dutch Anaesthesia Society. Of those, 655 (33.5%) were returned and could be used for analysis. The questionnaires assessed general work-related stress and satisfaction and anaesthesia-specific stress. A factor analysis was performed on the stress and satisfaction questionnaires. Personality traits were assessed using the Big Five Inventory. To identify personality profiles, a cluster analysis was performed on the Big Five Inventory. Scores of the extracted factors contributing to job stress and satisfaction were compared between the profiles we identified. Our analysis extracted six factors concerning general job stress. Of those, the emotionally difficult caseload contributed the most to job stress. The analysis also extracted four factors concerning general job satisfaction. Good relationships with patients and their families and being appreciated by colleagues contributed the most to satisfaction. The cluster analysis resulted in two distinct personality profiles: a distressed profile (n = 215) and a resilient profile (n = 440). General and anaesthesia-specific job stress was significantly higher and job satisfaction was significantly lower in the distressed profile, compared with the resilient profile. Experience of the emotionally difficult caseload did not differ between the two profiles CONCLUSION: Personality profiles were found to be related to anaesthesiologists' experience of work-related stress and satisfaction. One-third of the anaesthesiologists in our sample were categorised as distressed and are at risk of developing work-related mental health problems.


Adherence and Subthreshold Adherence in Sleep Apnea Subjects Receiving Positive Airway Pressure Therapy: A Retrospective Study Evaluating Differences in Adherence Versus Use.
Research on subthreshold compliance with positive airway pressure (PAP) therapy in sleep apnea patients may inform clinical sleep medicine practice. We retrospectively assessed compliant and subthreshold compliant sleep apnea subjects to test whether regular but fewer hours of PAP use would demonstrate clinically meaningful improvements and correlate with outcomes. A chart review was conducted of 113 consecutive sleep apnea subjects, naive to treatment, who completed a titration study and filled a PAP therapy prescription. Objective data categorized subjects into 3 groups: compliant, subthreshold compliant, and minimal use. Outcome measures assessed changes in insomnia, sleepiness, and nocturia on average 7 months from PAP initiation. Correlation coefficients analyzed dose-response relationships between hours of use and changes in outcomes. Among 113 PAP attempters, 104 (92%) were current users. Among 93 users with objective data, regular (consistent) PAP users included 59 compliant and 21 subthreshold compliant, and 13 subjects were minimal users. Compliant users averaging 6.6 ± 1.3 h/night and 42.0 ± 12.1 h/week showed the largest outcome improvements (all P < .05) with moderate to large effects for insomnia (d = 0.94), sleepiness (d = 0.58), and nocturia (d = 0.56). Subthreshold users averaging 4.1 ± 0.7 h/night but only 18.0 ± 5.6 h/week showed a large effect for insomnia (d = 0.76, P = .03) and nonsignificant, small effects for sleepiness (d = 0.38) and nocturia (d = 0.22). Correlation coefficients showed a trend for decrease in insomnia (P = .08; r = .20) and a significant decrease in nocturia (P = .034; r = 0.25), each in association with hours of PAP use. In a clinical sample, 86% of sleep apnea subjects regularly used PAP, but adherence was 63%. Regular users showed clinical treatment effects and potential dose-response relationships, suggesting that the term use offers advantages over the term adherence. Currently, subthreshold compliance may not merit insurance coverage in many countries, an issue affecting many sleep apnea patients.


RubiX: combining spatial resolutions for Bayesian inference of crossing fibers in diffusion MRI.
The trade-off between signal-to-noise ratio (SNR) and spatial specificity governs the choice of spatial resolution in magnetic resonance imaging (MRI); diffusion-weighted (DW) MRI is no exception. Images of lower resolution have higher signal to noise ratio, but also more partial volume artifacts. We present a data-fusion approach for tackling this trade-off by combining DW MRI data acquired both at high and low spatial resolution. We combine all data into a single Bayesian model to estimate the underlying fiber patterns and diffusion parameters. The proposed model, therefore, combines the benefits of each acquisition. We show that fiber crossings at the highest spatial resolution can be inferred more robustly and accurately using such a model compared to a simpler model that operates only on high-resolution data, when both approaches are matched for acquisition time.