CT findings of COVID-19 in follow-up: comparison between progression and recovery.
We aimed to retrospectively analyze the imaging changes detected in the follow-up of coronavirus disease 2019 (COVID-19) patients on thin-section computed tomography (CT). We included 54 patients diagnosed with COVID-19. The mean interval between the initial and follow-up CT scans was 7.82±3.74 days. Patients were divided into progression and recovery groups according to their outcomes. We evaluated CT images in terms of distribution of lesions and imaging manifestations. The manifestations included ground-glass opacity (GGO), crazy-paving pattern, consolidation, irregular line, and air bronchogram sign. COVID-19 lesions showed mainly subpleural distribution, which was accompanied by bronchovascular bundle distribution in nearly 30% of the patients. The lower lobes of both lungs were the most commonly involved. In the follow-up, the progression group showed more involvement of the upper lobe of the left lung than the recovery group. GGO was the most common sign. As the disease progressed, round GGO decreased and patchy GGO increased. On follow-up CT, consolidation increased in the progression group while decreasing in the recovery group. Air bronchogram sign was more commonly observed at the initial examination (90.9%) than at follow-up (30%) in the recovery group, but there was no significant change in the progression group. Pleural effusion and lymphadenopathy were absent in the initial examination, but pleural effusion was observed in three cases after follow-up. As COVID-19 progressed, round GGOs tended to evolve into patchy GGOs, consolidation increased, and pleural effusion could be occasionally observed. As COVID-19 resolved, the crazy-paving pattern and air bronchogram significantly decreased.


A biomechanical study of the relationship between running velocity and three-dimensional lumbosacral kinetics.
Faster running is not performed with proportional increase in all joint torque/work exertions. Although previous studies have investigated lumbopelvic kinetics for a single velocity, it is unclear whether each lumbopelvic torque should increase for faster running. We examined the relationship between running velocity and lumbopelvic kinetics. We calculated the three-dimensional lumbosacral kinetics of 10 male sprinters during steady-state running on a temporary indoor running track at five target velocities: 3.0 (3.20 ± 0.16), 4.5 (4.38 ± 0.18), 6.0 (5.69 ± 0.47), 7.5 (7.30 ± 0.41), and maximal sprinting (9.27 ± 0.36 m/s). The lumbosacral axial rotation torque increased more markedly (from 0.37 ± 0.06 to 1.99 ± 0.46 Nm/kg) than the extension and lateral flexion torques. The increase in the axial rotation torque was larger above 7.30 m/s. Conversely, the extension and lateral flexion torques plateaued when running velocity increased above 7.30 m/s. Similar results were observed for mechanical work. The results indicate that faster running required larger lumbosacral axial rotation torque. Conversely, the extension and lateral flexion torques were relatively invariant to running velocity above 7 m/s, implying that faster running below 7 m/s might increase the biomechanical loads causing excessive pelvic posterior tilt and excessive pelvic drop which has the potential to cause pain/injury related to lumbopelvic extensors and lateral flexors, whereas these biomechanical loads might not relate with running velocity above 7 m/s.


Generational shift in parental perceptions of overweight among school-aged children.
Parental perceptions of child's weight status may influence family readiness to foster healthy behaviors. This study investigated the generational shifting of parental perceptions about children's weight. Data were collected in the NHANES 1988-1994 (n = 2871) and 2005-2010 (n = 3202). Parents, mainly mothers, were asked whether they considered their child, ages 6 to 11 years, to be overweight, underweight, or just about the right weight. The Centers for Disease Control and Prevention 2000 growth chart was used for reference. We ran Poisson regression to estimate the probability ratio between the 2 surveys for parents perceiving their child as overweight after controlling for actual weight. The 10th percentile of BMI z scores for children who were parentally perceived as overweight shifted with statistical significance from 84th percentile of reference population in the early survey to 91st percentile of reference population in the recent survey (P < .05). The mean z score of children parentally perceived as overweight also increased between surveys with the largest increase among children from poor families (from 1.60 [SE: 0.20] to 1.98 [0.08], P < .05), followed by African Americans (from 1.65 [0.09] to 2.02 [0.05], P < .05). The probability of overweight/obese children being correctly perceived as overweight by the parents declined by 24% between surveys (probability ratio = 0.76 [95% confidence interval: 0.67-0.87]). Overweight/obese children were less likely to be perceived as overweight in the recent survey compared with peers of similar weight but surveyed 10+ years earlier. The declining tendency among parents to perceive overweight children appropriately may indicate a generational shift in social norms related to body weight.


Loss of nuclear PTEN in HCV-infected human hepatocytes.
Hepatitis C virus (HCV) infection is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC); however, the mechanism of HCV-mediated hepatocarcinogenesis is not well understood. Insufficiency of PTEN tumor suppressor is associated with more aggressive cancers, including HCC. We asked whether viral non-coding RNA could initiate oncogenesis in HCV infected human hepatocytes. The results presented herein suggest that loss of nuclear PTEN in HCV-infected human hepatocytes results from depletion of Transportin-2, which is a direct target of viral non-coding RNA, vmr11. The intracellular distribution of PTEN in HCV-infected cells was monitored by immunostaining and Western blots of nuclear and cytoplasmic proteins. Effects of PTEN depletion were examined by comparing expression arrays of uninfected cells with either HCV-infected or vmr11-transfected cells. Target genes suggested by array analyses were validated by Western blot. The influence of nuclear PTEN deficiency on virus production was determined by quantitative analysis of HCV genomic RNA in culture media of infected hepatocytes. Import of PTEN to the nucleus relies on the interaction of Transportin-2 and PTEN proteins; we show that depletion of Transportin-2 by HCV infection or by the introduction of vmr11 in uninfected cells results in reduced nuclear PTEN. In turn, nuclear PTEN insufficiency correlates with increased virus production and the induction of γ-H2AX, a marker of DNA double-strand breaks and genomic instability. An HCV-derived small non-coding RNA inhibits Transportin-2 and PTEN translocation to the nucleus, suggesting a direct viral role in hepatic oncogenesis.


Characterization of the flexible genome complement of the commensal Escherichia coli strain A0 34/86 (O83 : K24 : H31).
Colonization by the commensal Escherichia coli strain A0 34/86 (O83 : K24 : H31) has proved to be safe and efficient in the prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants in Czech paediatric clinics over the past three decades. In searching for traits contributing to this beneficial effect related to the gut colonization capacity of the strain, the authors have analysed its genome by DNA-DNA hybridization to E. coli K-12 (MG1655) genomic DNA arrays and to 'Pathoarrays', as well as by multiplex PCR, bacterial artificial chromosome (BAC) library cloning and shotgun sequencing. Four hundred and ten E. coli K-12 ORFs were absent from A0 34/86, while 72 out of 456 genes associated with pathogenicity islands of E. coli and Shigella were also detected in E. coli A0 34/86. Furthermore, extraintestinal pathogenic E. coli-related genes involved in iron uptake and adhesion were detected by multiplex PCR, and genes encoding the HlyA and cytotoxic necrotizing factor toxins, together with 21 genes of the uropathogenic E. coli 536 pathogenicity island II, were identified by analysis of 2304 shotgun and 1344 BAC clone sequences of A0 34/86 DNA. Multiple sequence comparisons identified 31 kb of DNA specific for E. coli A0 34/86; some of the genes carried by this DNA may prove to be implicated in the colonization capacity of the strain, enabling it to outcompete pathogens. Among 100 examined BAC clones roughly covering the A0 34/86 genome, one reproducibly conferred on the laboratory strain DH10B an enhanced capacity to persist in the intestine of newborn piglets. Sequencing revealed that this BAC clone carried gene clusters encoding gluconate and mannonate metabolism, adhesion (fim), invasion (ibe) and restriction/modification functions. Hence, the genome of this clinically safe and highly efficient colonizer strain appears to harbour many 'virulence-associated' genes. These results highlight the thin line between bacterial 'virulence' and 'fitness' or 'colonization' factors, and question the definition of enterobacterial virulence factors.


Controlled drug release from ultrasound-visualized elastic eccentric microcapsules using different resonant modes.
Ultrasound controlled drug delivery and release has attracted increased attention for targeted delivery of drug. In this report, we present a strategy for targeted drug delivery by using ultrasound to image the location of drug carriers, as well as simultaneously controlling the release rate of drug from elastic eccentric microcapsules (EEMs), based on their mode shapes (MSs) and resonant natural frequencies (NFs). We prepared a series of EEMs with various diameters of inner spherical cavities using a microfluidic chip. The EEMs could be visualized by an ultrasound imaging system within a tissue mimic (i.e. phantom). Using theoretical modeling techniques, we investigated the effects of MSs and NFs on the resonant modes of EEMs. Guided by this modelling, we applied external ultrasonic stimuli at various levels of low frequency to regulate the release rate of Rhodamine 6G (R6G, as a model drug) from EEMs. To further demonstrate the control of drug release and evaluate the efficacy of the encapsulated drugs on cancer cells, we released an anticancer drug, doxorubicin hydrochloride (DOX), from the EEMs and tested the viability of cancer cells in vitro. The results show that this novel strategy holds great promise towards development of a controlled drug release system visualized and triggered by ultrasound.


From inert matter to the global society life as multi-level networks of processes.
A few billion years have passed since the first life forms appeared. Since then, life has continued to forge complex associations between the different emergent levels of interconnection it forms. The advances of recent decades in molecular chemistry and theoretical biology, which have embraced complex systems approaches, now make it possible to conceptualize the questions of the origins of life and its increasing complexity from three complementary notions of closure: processes closure, autocatalytic closure and constraints closure. Developed in the wake of the second-order cybernetics, this triple closure approach, that relies on graph theory and complex networks science, sketch a paradigm where it is possible to go up the physical levels of organization of matter, from physics to biology and society, without resorting to strong reductionism. The phenomenon of life is conceived as the contingent complexification of the organization of matter, until the emergence of life forms, defined as a network of auto-catalytic process networks, organized in a multi-level manner. This approach of living systems, initiated by Maturana & Varela and Kauffman, inevitably leads to a reflection on the nature of cognition; and in the face of the deep changes that affected humanity as a complex systems, on the nature of cultural evolution. Faced with the major challenges that humanity will have to address in the decades to come, this new paradigm invites us to change our conception of causality by shifting our attention from state change to process change and to abandon a widespread notion of 'local' causality in favour of complex systems thinking. It also highlights the importance of a better understanding of the influence of social networks, recommendation systems and artificial intelligence on our future collective dynamics and social cognition processes. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.


A large and persistent carbon sink in the world's forests.
The terrestrial carbon sink has been large in recent decades, but its size and location remain uncertain. Using forest inventory data and long-term ecosystem carbon studies, we estimate a total forest sink of 2.4 ± 0.4 petagrams of carbon per year (Pg C year(-1)) globally for 1990 to 2007. We also estimate a source of 1.3 ± 0.7 Pg C year(-1) from tropical land-use change, consisting of a gross tropical deforestation emission of 2.9 ± 0.5 Pg C year(-1) partially compensated by a carbon sink in tropical forest regrowth of 1.6 ± 0.5 Pg C year(-1). Together, the fluxes comprise a net global forest sink of 1.1 ± 0.8 Pg C year(-1), with tropical estimates having the largest uncertainties. Our total forest sink estimate is equivalent in magnitude to the terrestrial sink deduced from fossil fuel emissions and land-use change sources minus ocean and atmospheric sinks.


Interhemispheric integration of visual processing during task-driven lateralization.
The mechanisms underlying interhemispheric integration (IHI) remain poorly understood, particularly for lateralized cognitive processes. To test competing theories of IHI, we constructed and fitted dynamic causal models to functional magnetic resonance data from two visual tasks that operated on identical stimuli but showed opposite hemispheric dominance. Using a systematic Bayesian model selection procedure, we found that, in the ventral visual stream, which was activated by letter judgments, interhemispheric connections mediated asymmetric information transfer from the nonspecialized right to the specialized left hemisphere when the latter did not have direct access to stimulus information. Notably, this form of IHI did not engage all areas activated by the task but was specific for areas in the lingual and fusiform gyri. In the dorsal stream, activated by spatial judgments, it did not matter which hemisphere received the stimulus: interhemispheric coupling increased bidirectionally, reflecting recruitment of the nonspecialized left hemisphere. Again, not all areas activated by the task were involved in this form of IHI; instead, it was restricted to interactions between areas in the superior parietal gyrus. Overall, our results provide direct neurophysiological evidence, in terms of effective connectivity, for the existence of context-dependent mechanisms of IHI that are implemented by specific visual areas during task-driven lateralization.


Is accurate, positive, or inflated self-perception most advantageous for psychological adjustment? A competitive test of key hypotheses.
Empirical research on the (mal-)adaptiveness of favorable self-perceptions, self-enhancement, and self-knowledge has typically applied a classical null-hypothesis testing approach and provided mixed and even contradictory findings. Using data from 5 studies (laboratory and field, total N = 2,823), we used an information-theoretic approach combined with Response Surface Analysis to provide the first competitive test of 6 popular hypotheses: that more favorable self-perceptions are adaptive versus maladaptive (Hypotheses 1 and 2: Positivity of self-view hypotheses), that higher levels of self-enhancement (i.e., a higher discrepancy of self-viewed and objectively assessed ability) are adaptive versus maladaptive (Hypotheses 3 and 4: Self-enhancement hypotheses), that accurate self-perceptions are adaptive (Hypothesis 5: Self-knowledge hypothesis), and that a slight degree of self-enhancement is adaptive (Hypothesis 6: Optimal margin hypothesis). We considered self-perceptions and objective ability measures in two content domains (reasoning ability, vocabulary knowledge) and investigated 6 indicators of intra- and interpersonal psychological adjustment. Results showed that most adjustment indicators were best predicted by the positivity of self-perceptions. There were some specific self-enhancement effects, and evidence generally spoke against the self-knowledge and optimal margin hypotheses. Our results highlight the need for comprehensive and simultaneous tests of competing hypotheses. Implications for the understanding of underlying processes are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Loss of Fas-ligand expression in mouse keratinocytes during UV carcinogenesis.
Skin cells containing excessive ultraviolet (UV) radiation-induced DNA damage are eliminated by apoptosis that involves the p53 pathway and Fas/Fas-Ligand (Fas-L) interactions. To determine whether dysregulation of apoptosis plays a role in skin cancer development through disruption of Fas/Fas-L interactions, hairless SKH-hr1 mice were exposed to chronic UV irradiation from Kodacel-filtered FS40 lamps for 30 weeks. Their skin was analyzed for the presence of sunburn cells (apoptotic keratinocytes) and for Fas and Fas-L expression at various time points. A dramatic decrease in the numbers of morphologically identified sunburn cells and TUNEL-positive cells was detected as early as 1 week after chronic UV exposure began. After 4 weeks of chronic UV exposure, these cells were barely detectable. This defect in apoptosis was paralleled by an initial decrease in Fas-L expression during the first week of chronic UV irradiation and a complete loss of expression after 4 weeks. Fas expression, however, increased during the course of chronic UV exposure. p53 mutations were detected in the UV-irradiated epidermis as early as 1 week after irradiation began and continued to accumulate with further UV exposure. Mice exposed to chronic UV began to develop skin tumors after approximately 8 weeks, and all mice had multiple skin tumors by 24 weeks. Most of the tumors expressed Fas but not Fas-L. We conclude that chronic UV exposure may induce a loss of Fas-L expression and a gain in p53 mutations, leading to dysregulation of apoptosis, expansion of mutated keratinocytes, and initiation of skin cancer.


Spirituality and Religiosity in Adolescents Living With Sickle Cell Disease.
This study purports to address paucity in the literature regarding how adolescents with sickle cell disease (SCD) describe and experience spirituality and religiosity (S/R). This was a qualitative descriptive study. Two semi-structured interviews were conducted with nine adolescents (Mage = 16.2 years). Data were analyzed using a template analysis style and a concurrent analysis process of data reduction. Three major themes encompassed the participants' descriptions of the relationships between S/R, health and illness in their lives including S/R as sources for coping, influence of S/R beliefs on health and illness, and sharing S/R with Health Care Providers (HCPs). S/R as coping mechanisms included six threads: interconnecting with God, interconnecting with others, interconnecting with creative arts, scriptural metanarratives, transcendent experiences, and acceptance and finding meaning. Expectations of health providers included two threads: Religiosity is private/personal and sharing spiritual and religious beliefs is risky. S/R are particularly salient for adolescents with SCD.


Evaluation of a digitally-enabled care pathway for acute kidney injury management in hospital emergency admissions.
We developed a digitally enabled care pathway for acute kidney injury (AKI) management incorporating a mobile detection application, specialist clinical response team and care protocol. Clinical outcome data were collected from adults with AKI on emergency admission before (May 2016 to January 2017) and after (May to September 2017) deployment at the intervention site and another not receiving the intervention. Changes in primary outcome (serum creatinine recovery to ≤120% baseline at hospital discharge) and secondary outcomes (30-day survival, renal replacement therapy, renal or intensive care unit (ICU) admission, worsening AKI stage and length of stay) were measured using interrupted time-series regression. Processes of care data (time to AKI recognition, time to treatment) were extracted from casenotes, and compared over two 9-month periods before and after implementation (January to September 2016 and 2017, respectively) using pre-post analysis. There was no step change in renal recovery or any of the secondary outcomes. Trends for creatinine recovery rates (estimated odds ratio (OR) = 1.04, 95% confidence interval (95% CI): 1.00-1.08, p = 0.038) and renal or ICU admission (OR = 0.95, 95% CI: 0.90-1.00, p = 0.044) improved significantly at the intervention site. However, difference-in-difference analyses between sites for creatinine recovery (estimated OR = 0.95, 95% CI: 0.90-1.00, p = 0.053) and renal or ICU admission (OR = 1.06, 95% CI: 0.98-1.16, p = 0.140) were not significant. Among process measures, time to AKI recognition and treatment of nephrotoxicity improved significantly (p < 0.001 and 0.047 respectively).


Drug resistance in Plasmodium falciparum from the Chittagong Hill Tracts, Bangladesh.
To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh.


Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors.
Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.


Experiences with web search on medical concerns and self diagnosis.
The wealth of medical information on the Web makes it convenient for non-experts to conduct their own diagnosis and healthcare assessment based on limited knowledge of signs, symptoms, and disorders. We present the findings of a survey aimed at exploring laypeoples' activities and experiences with using Web search to pursue explanations for symptoms. Survey findings suggest that the Web may influence anxiety levels and behaviors of those searching for information on undiagnosed conditions. A better understanding of consumer experience regarding the use of the Web to interpret symptoms can assist in the refinement of healthcare content and retrieval.


Advancing the match-mismatch framework for large herbivores in the Arctic: Evaluating the evidence for a trophic mismatch in caribou.
Climate-induced shifts in plant phenology may adversely affect animals that cannot or do not shift the timing of their reproductive cycle. The realized effect of potential trophic "mismatches" between a consumer and its food varies with the degree to which species rely on dietary income and stored capital. Large Arctic herbivores rely heavily on maternal capital to reproduce and give birth near the onset of the growing season but are they vulnerable to trophic mismatch? We evaluated the long-term changes in the temperatures and characteristics of the growing seasons (1970-2013), and compared growing conditions and dynamics of forage quality for caribou at peak parturition, peak lactation, and peak forage biomass, and plant senescence between two distinct time periods over 36 years (1977 and 2011-13). Despite advanced thaw dates (7-12 days earlier), increased growing season lengths (15-21 days longer), and consistent parturition dates, we found no decline in forage quality and therefore no evidence within this dataset for a trophic mismatch at peak parturition or peak lactation from 1977 to 2011-13. In Arctic ungulates that use stored capital for reproduction, reproductive demands are largely met by body stores deposited in the previous summer and autumn, which reduces potential adverse effects of any mismatch between food availability and timing of parturition. Climate-induced effects on forages growing in the summer and autumn ranges, however, do correspond with the demands of female caribou and their offspring to gain mass for the next reproductive cycle and winter. Therefore, we suggest the window of time to examine the match-mismatch framework in Arctic ungulates is not at parturition but in late summer-autumn, where the multiplier effects of small changes in forage quality are amplified by forage abundance, peak forage intake, and resultant mass gains in mother-offspring pairs.


Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only.
The goal of this study is to describe complications and outcomes of prehospital ketamine use for agitation as compared to other methods of physical or chemical restraint such as haloperidol plus benzodiazepine or physical restraint only. We conducted a single-center retrospective review of patient encounters in which restraint was administered in the prehospital setting. At the beginning of our study window, only physical restraint was available to paramedics managing agitated patients but subsequently, haloperidol and benzodiazepines were introduced, followed by ketamine 2 years later. By comparing patients before and after each transition, we divided subjects into 3 cohorts based on restraint type: physical restraint, haloperidol plus benzodiazepine, and ketamine. Demographic data were collected, and outcome measures included intubation rate, need for additional physical or chemical restraint, emergency department (ED) length of stay, need for hospital admission, and employee injury. Of 214 subjects included in the study, 95 patients were administered ketamine, 68 received haloperidol and benzodiazepine, and 51 were physically restrained. Eleven of the patients (11.6%) who received ketamine were intubated. Compared to patients who received haloperidol plus benzodiazepine, patients who received ketamine were more likely to be intubated (odds ratio [OR] = 8.77, 95% confidence interval [CI], 1.10-69.68) and were more likely to require additional chemical restraint when compared to haloperidol/benzodiazepine or physical restraint only (OR =2.94, 95% CI, 1.49-5.80, and OR =2.15, 95% CI, 1.07-4.31, respectively). There were no differences between the 2 chemical sedation groups in terms of ED length of stay or hospital admission rate. This study demonstrates a lower intubation rate in patients administered ketamine than prior literature in association with a lower weight-based dosing regimen. Ketamine use was correlated with a higher frequency of intubation and a greater need for additional chemical restraint when compared with other restraint modalities, though exogenous factors such as provider preference may have impacted this result. There was no difference in ED length of stay or admission rate between the ketamine and haloperidol plus benzodiazepine groups. Further prospective study is needed to determine whether there is a subset of patients for whom ketamine would be beneficial compared to other therapies.


Neural portraits of perception: reconstructing face images from evoked brain activity.
Recent neuroimaging advances have allowed visual experience to be reconstructed from patterns of brain activity. While neural reconstructions have ranged in complexity, they have relied almost exclusively on retinotopic mappings between visual input and activity in early visual cortex. However, subjective perceptual information is tied more closely to higher-level cortical regions that have not yet been used as the primary basis for neural reconstructions. Furthermore, no reconstruction studies to date have reported reconstructions of face images, which activate a highly distributed cortical network. Thus, we investigated (a) whether individual face images could be accurately reconstructed from distributed patterns of neural activity, and (b) whether this could be achieved even when excluding activity within occipital cortex. Our approach involved four steps. (1) Principal component analysis (PCA) was used to identify components that efficiently represented a set of training faces. (2) The identified components were then mapped, using a machine learning algorithm, to fMRI activity collected during viewing of the training faces. (3) Based on activity elicited by a new set of test faces, the algorithm predicted associated component scores. (4) Finally, these scores were transformed into reconstructed images. Using both objective and subjective validation measures, we show that our methods yield strikingly accurate neural reconstructions of faces even when excluding occipital cortex. This methodology not only represents a novel and promising approach for investigating face perception, but also suggests avenues for reconstructing 'offline' visual experiences-including dreams, memories, and imagination-which are chiefly represented in higher-level cortical areas.


Ultrastructural modeling of small angle scattering from photosynthetic membranes.
The last decade has seen a range of studies using non-invasive neutron and X-ray techniques to probe the ultrastructure of a variety of photosynthetic membrane systems. A common denominator in this work is the lack of an explicitly formulated underlying structural model, ultimately leading to ambiguity in the data interpretation. Here we formulate and implement a full mathematical model of the scattering from a stacked double bilayer membrane system taking instrumental resolution and polydispersity into account. We validate our model by direct simulation of scattering patterns from 3D structural models. Most importantly, we demonstrate that the full scattering curves from three structurally typical cyanobacterial thylakoid membrane systems measured in vivo can all be described within this framework. The model provides realistic estimates of key structural parameters in the thylakoid membrane, in particular the overall stacking distance and how this is divided between membranes, lumen and cytoplasmic liquid. Finally, from fitted scattering length densities it becomes clear that the protein content in the inner lumen has to be lower than in the outer cytoplasmic liquid and we extract the first quantitative measure of the luminal protein content in a living cyanobacteria.


Stem cells for heart valve regeneration.
Heart valve tissue engineering holds the potential to overcome limitations of currently used heart valve prostheses. It involves the isolation and expansion of autologous patient cells, the subsequent seeding of these cells onto an appropriate scaffold material, the in vitro incubation and the in vivo implantation of the derived tissue-engineered construct into the patient from whom the cells were taken. While vascular-derived cells require harvest of intact donor tissue and show limited expansion capacities, the use of stem or progenitor cells may overcome these limitations and expand the versatility of the concept of heart valve tissue engineering. Possible sources include cells isolated from blood, bone marrow, adipose tissue, amniotic fluid, chorionic villi, umbilical cord and induced pluripotent stem cells. Here we review different stem cell sources with particular regard to cellular phenotypes and their suitability for application in heart valve tissue engineering.


Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures.
Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety.


Highly overlapping winter diet in two sympatric lemming species revealed by DNA metabarcoding.
Sympatric species are expected to minimize competition by partitioning resources, especially when these are limited. Herbivores inhabiting the High Arctic in winter are a prime example of a situation where food availability is anticipated to be low, and thus reduced diet overlap is expected. We present here the first assessment of diet overlap of high arctic lemmings during winter based on DNA metabarcoding of feces. In contrast to previous analyses based on microhistology, we found that the diets of both collared (Dicrostonyx groenlandicus) and brown lemmings (Lemmus trimucronatus) on Bylot Island were dominated by Salix while mosses, which were significantly consumed only by the brown lemming, were a relatively minor food item. The most abundant plant taxon, Cassiope tetragona, which alone composes more than 50% of the available plant biomass, was not detected in feces and can thus be considered to be non-food. Most plant taxa that were identified as food items were consumed in proportion to their availability and none were clearly selected for. The resulting high diet overlap, together with a lack of habitat segregation, indicates a high potential for resource competition between the two lemming species. However, Salix is abundant in the winter habitats of lemmings on Bylot Island and the non-Salix portion of the diets differed between the two species. Also, lemming grazing impact on vegetation during winter in the study area is negligible. Hence, it seems likely that the high potential for resource competition predicted between these two species did not translate into actual competition. This illustrates that even in environments with low primary productivity food resources do not necessarily generate strong competition among herbivores.


The survival of donor-derived cells in a successfully grafted corneal button 10 years after penetrating keratoplasty for lattice dystrophy.
To investigate the survival of donor-derived cells in a successfully grafted corneal button 10 years after penetrating keratoplasty for lattice dystrophy. In 1996, a 48-year-old male with lattice corneal dystrophy underwent penetrating keratoplasty 3 times in the right eye within a 3-month interval. Nine years and 7 months later, the patient underwent a fourth penetrating keratoplasty. After surgery, the previous graft was analyzed to determine the origin of the cells. The epithelium and endothelium were removed, and then the button was dissected into 5 stromal blocks measuring 2 x 1.8 mm. Tissues underwent forensic genotyping using 16 markers (amelogenin for sex chromosomes and 15 autosomal short tandem repeats). Patient buccal tissue DNA was used as a control. The epithelium and buccal tissue contained identical DNA (i.e. recipient DNA). Similarly, the most peripheral stromal tissue contained only recipient DNA. In contrast, the most central stromal tissue only contained DNA of nonrecipient origin (presumably donor), while the stromal tissue between the periphery and center contained both recipient and nonrecipient DNA. The corneal stroma was infiltrated by surrounding recipient-derived keratocytes from the periphery. Therefore, more donor-derived cells had survived in the central stroma.


Effective Usability Engineering in Healthcare: A Vision of Usable and Safer Healthcare IT.
Persistent problems with healthcare IT that is unusable and unsafe have been reported worldwide. In this paper we present our vision for deploying usability engineering in healthcare in a more substantive way in order to improve the current situation. The argument will be made that stronger and more substantial efforts need to be made to bring multiple usability engineering methods to bear on points in both system design and deployment (and not just as a one-time effort restricted to software product development). In addition, improved processes for ensuring the usability of commercial vendor-based systems being implemented in healthcare organizations need to be addressed. A discussion will also be provided on challenges and barriers that will need to be overcome to ensure that the heatlhcare IT that is released is both usable and safe.


Understanding uncertainty in temperature effects on vector-borne disease: a Bayesian approach.
Extrinsic environmental factors influence the distribution and population dynamics of many organisms, including insects that are of concern for human health and agriculture. This is particularly true for vector-borne infectious diseases like malaria, which is a major source of morbidity and mortality in humans. Understanding the mechanistic links between environment and population processes for these diseases is key to predicting the consequences of climate change on transmission and for developing effective interventions. An important measure of the intensity of disease transmission is the reproductive number R0. However, understanding the mechanisms linking R0 and temperature, an environmental factor driving disease risk, can be challenging because the data available for parameterization are often poor. To address this, we show how a Bayesian approach can help identify critical uncertainties in components of R0 and how this uncertainty is propagated into the estimate of R0. Most notably, we find that different parameters dominate the uncertainty at different temperature regimes: bite rate from 15 degrees C to 25 degrees C; fecundity across all temperatures, but especially approximately 25-32 degrees C; mortality from 20 degrees C to 30 degrees C; parasite development rate at degrees 15-16 degrees C and again at approximately 33-35 degrees C. Focusing empirical studies on these parameters and corresponding temperature ranges would be the most efficient way to improve estimates of R0. While we focus on malaria, our methods apply to improving process-based models more generally, including epidemiological, physiological niche, and species distribution models.


Segmented Linear Regression Modelling of Time-Series of Binary Variables in Healthcare.
In healthcare, change is usually detected by statistical techniques comparing outcomes before and after an intervention. A common problem faced by researchers is distinguishing change due to secular trends from change due to an intervention. Interrupted time-series analysis has been shown to be effective in describing trends in retrospective time-series and in detecting change, but methods are often biased towards the point of the intervention. Binary outcomes are typically modelled by logistic regression where the log-odds of the binary event is expressed as a function of covariates such as time, making model parameters difficult to interpret. The aim of this study was to present a technique that directly models the probability of binary events to describe change patterns using linear sections. We describe a modelling method that fits progressively more complex linear sections to the time-series of binary variables. Model fitting uses maximum likelihood optimisation and models are compared for goodness of fit using Akaike's Information Criterion. The best model describes the most likely change scenario. We applied this modelling technique to evaluate hip fracture patient mortality rate for a total of 2777 patients over a 6-year period, before and after the introduction of a dedicated hip fracture unit (HFU) at a Level 1, Major Trauma Centre. The proposed modelling technique revealed time-dependent trends that explained how the implementation of the HFU influenced mortality rate in patients sustaining proximal femoral fragility fractures. The technique allowed modelling of the entire time-series without bias to the point of intervention. Modelling the binary variable of interest directly, as opposed to a transformed variable, improved the interpretability of the results. The proposed segmented linear regression modelling technique using maximum likelihood estimation can be employed to effectively detect trends in time-series of binary variables in retrospective studies.


Representation learning of genomic sequence motifs with convolutional neural networks.
Although convolutional neural networks (CNNs) have been applied to a variety of computational genomics problems, there remains a large gap in our understanding of how they build representations of regulatory genomic sequences. Here we perform systematic experiments on synthetic sequences to reveal how CNN architecture, specifically convolutional filter size and max-pooling, influences the extent that sequence motif representations are learned by first layer filters. We find that CNNs designed to foster hierarchical representation learning of sequence motifs-assembling partial features into whole features in deeper layers-tend to learn distributed representations, i.e. partial motifs. On the other hand, CNNs that are designed to limit the ability to hierarchically build sequence motif representations in deeper layers tend to learn more interpretable localist representations, i.e. whole motifs. We then validate that this representation learning principle established from synthetic sequences generalizes to in vivo sequences.


Effect of time of day of recreational and household physical activity on prostate and breast cancer risk (MCC-Spain study).
Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined in a population-based case-control study (MCC-Spain) if the time-of-day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in-person interviews. Information on time-of-day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008-2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8-10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48-1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44-1.20); meta-OR for the two cancers combined 0.74 (95%CI = 0.53-1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45-1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population-based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention.


Analysis of a bac operon-silenced strain suggests pleiotropic effects of bacilysin in Bacillus subtilis.
Bacilysin, as the simplest peptide antibiotic made up of only L-alanine and L-anticapsin, is produced and excreted by Bacillus subtilis under the control of quorum sensing. We analyzed bacilysin-nonproducing strain OGU1 which was obtained by bacA-targeted pMutin T3 insertion into the parental strain genome resulting in a genomic organization (bacA'::lacZ::erm::bacABCDEF) to form an IPTG-inducible bac operon. Although IPTG induction provided 3- to 5-fold increment in the transcription of bac operon genes, no bacilysin activity was detectable in bioassays and inability of the OGU1 to form bacilysin was confirmed by UPLC-mass spectrometry analysis. Phenotypic analyses revealed the deficiencies in OGU1 with respect to colony pigmentation, spore coat proteins, spore resistance and germination, which could be rescued by external addition of bacilysin concentrate into its cultures. 2DE MALDI-TOF/MS and nanoLC-MS/MS were used as complementary approaches to compare cytosolic proteomes of OGU1. 2-DE identified 159 differentially expressed proteins corresponding to 121 distinct ORFs. In nanoLC-MS/MS, 76 proteins were differentially expressed in OGU1. Quantitative transcript analyses of selected genes validated the proteomic findings. Overall, the results pointed to the impact of bacilysin on expression of certain proteins of sporulation and morphogenesis; the members of mother cell compartment-specific σE and σK regulons in particular, quorum sensing and two component-global regulatory systems, peptide transport, stress response as well as CodY- and ScoC-regulated proteins.


Supporting performance in the face of age-related neural changes: testing mechanistic roles of cognitive reserve.
Age impacts multiple neural measures and these changes do not always directly translate into alterations in clinical and cognitive measures. This partial protection from the deleterious effects of age in some individuals is referred to as cognitive reserve (CR) and although linked to variations in intelligence and life experiences, its mechanism is still unclear. Within the framework of a theoretical model we tested two potential mechanistic roles of CR to maintain task performance, neural reserve and neural compensation, in young and older adults using functional and structural MRI. Neural reserve refers to increased efficiency and/or capacity of existing functional neural resources. Neural compensation refers to the increased ability to recruit new, additional functional resources. Using structural and functional measures and task performance, the roles of CR were tested using path analysis. Results supported both mechanistic theories of CR and the use of our general theoretical model.


Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan.
To determine the prevalence of diabetes mellitus and IGT in the Funagata area of Japan. The total eligible subjects was 1163, all were > or = 45 yr of age, and 52 were known diabetic patients. Data collected included body height, weight, and answers to medical questionnaires. A 75-g OGTT was done in the morning. WHO criteria were used to classify the current diabetes status of study participants. Of the 1111 scheduled for the OGTT, 868 took the test; the participation rate was 77.8%. The prevalence of diabetes was 10.5 and 12.9%, and the prevalence of IGT was 14.7 and 18.0% for men and women, respectively. The prevalence of undiagnosed diabetes (4.9%) was almost equal to that of previously diagnosed diabetes (4.5%). The prevalence of diabetes in the Funagata area was two to four times higher than that of previous reports in Japan, in which many investigators used a urinary glucose test as a preliminary test. This difference is attributed to the method of determining the prevalence of diabetes.


Diabetes-induced changes in specific lipid molecular species in rat myocardium.
Intrinsic cardiac dysfunction during the diabetic state has been causally linked to changes in myocardial lipid metabolism. However, the precise alterations in the molecular species of myocardial polar and non-polar lipids during the diabetic state and their responses to insulin have not been investigated. Herein we demonstrate four specific alterations in rat myocardial lipid molecular species after induction of the diabetic state by streptozotocin treatment: (i) a massive remodelling of triacylglycerol molecular species including a >5-fold increase in tripalmitin mass and a 60% decrease in polyunsaturated triacylglycerol molecular species mass (i.e. triacylglycerols containing at least one acyl residue with more than two double bonds); (ii) a 46% increase in myocardial phosphatidylinositol mass; (iii) a 44% increase in myocardial plasmenylethanolamine mass and (iv) a 22% decrease in 1-stearoyl-2-arachidonoyl phosphatidylethanolamine content. Each of the changes in phospholipid classes, subclasses and individual molecular species were prevented by insulin treatment after induction of the diabetic state. In sharp contrast, the alterations in triacylglycerol molecular species were not preventable by peripheral insulin treatment after induction of the diabetic state. These results segregate diabetes-induced alterations in myocardial lipid metabolism into changes that can be remedied or not by routine peripheral insulin treatment and suggest that peripheral insulin therapy alone may not be sufficient to correct all of the metabolic alterations present in diabetic myocardium.


Probing the accuracy and precision of Hirshfeld atom refinement with HARt interfaced with Olex2.
Hirshfeld atom refinement (HAR) is a novel X-ray structure refinement technique that employs aspherical atomic scattering factors obtained from stockholder partitioning of a theoretically determined tailor-made static electron density. HAR overcomes many of the known limitations of independent atom modelling (IAM), such as too short element-hydrogen distances, r(X-H), or too large atomic displacement parameters (ADPs). This study probes the accuracy and precision of anisotropic hydrogen and non-hydrogen ADPs and of r(X-H) values obtained from HAR. These quantities are compared and found to agree with those obtained from (i) accurate neutron diffraction data measured at the same temperatures as the X-ray data and (ii) multipole modelling (MM), an established alternative method for interpreting X-ray diffraction data with the help of aspherical atomic scattering factors. Results are presented for three chemically different systems: the aromatic hydro-carbon rubrene (orthorhombic 5,6,11,12-tetra-phenyl-tetracene), a co-crystal of zwitterionic betaine, imidazolium cations and picrate anions (BIPa), and the salt potassium hydrogen oxalate (KHOx). The non-hydrogen HAR-ADPs are as accurate and precise as the MM-ADPs. Both show excellent agreement with the neutron-based values and are superior to IAM-ADPs. The anisotropic hydrogen HAR-ADPs show a somewhat larger deviation from neutron-based values than the hydrogen SHADE-ADPs used in MM. Element-hydrogen bond lengths from HAR are in excellent agreement with those obtained from neutron diffraction experiments, although they are somewhat less precise. The residual density contour maps after HAR show fewer features than those after MM. Calculating the static electron density with the def2-TZVP basis set instead of the simpler def2-SVP one does not improve the refinement results significantly. All HARs were performed within the recently introduced HARt option implemented in the Olex2 program. They are easily launched inside its graphical user interface following a conventional IAM.


Heme distortion modulated by ligand-protein interactions in inducible nitric-oxide synthase.
The catalytic center of nitric-oxide synthase (NOS) consists of a thiolate-coordinated heme macrocycle, a tetrahydrobiopterin (H4B) cofactor, and an l-arginine (l-Arg)/N-hydroxyarginine substrate binding site. To determine how the interplay between the cofactor, the substrates, and the protein matrix housing the heme regulates the enzymatic activity of NOS, the CO-, NO-, and CN(-)-bound adducts of the oxygenase domain of the inducible isoform of NOS (iNOS(oxy)) were examined with resonance Raman spectroscopy. The Raman data of the CO-bound ferrous protein demonstrated that the presence of l-Arg causes the Fe-C-O moiety to adopt a bent structure because of an H-bonding interaction whereas H4B binding exerts no effect. Similar behavior was found in the CN(-)-bound ferric protein and in the nitric oxide (NO)-bound ferrous protein. In contrast, in the NO-bound ferric complexes, the addition of l-Arg alone does not affect the structural properties of the Fe-N-O moiety, but H4B binding forces it to adopt a bent structure, which is further enhanced by the subsequent addition of l-Arg. The differential interactions between the various heme ligands and the protein matrix in response to l-Arg and/or H4B binding is coupled to heme distortions, as reflected by the development of a variety of out-of-plane heme modes in the low frequency Raman spectra. The extent and symmetry of heme deformation modulated by ligand, substrate, and cofactor binding may provide important control over the catalytic and autoinhibitory properties of the enzyme.


Work-Up and Outcome of Hepatic Resection for Peri-Hilar Cholangiocarcinoma (PH-CCA) without Staging Laparoscopy.
Background: This study reports the outcome of a work-up programme for resection of peri-hilar cholangiocarcinoma (PH-CCA) without the use of staging laparoscopy. Methods: This is a clinical case cohort series of patients undergoing surgical resection of PH-CCA without the use of staging laparoscopy in the work-up algorithm. During the 13 years from 1 January 2009 to 1 January 2022, 32 patients underwent laparotomy for planned surgical resection of PH-CCA. Data were collected on demographic profile, admission biochemistry, radiology, pre-operative intervention, operation and outcome, together with post-operative complications and disease-free and overall survival. Results: All patients underwent pre-operative contrast-enhanced CT. Twenty-four (75%) underwent pre-operative MR. Twenty-three (72%) underwent pre-operative biliary drainage. Twenty-nine patients (91%) had either type III or IV peri-hilar cholangiocarcinoma. One patient (3%) in this series underwent a non-resectional laparotomy. Twenty-nine (91%) had a final histopathological diagnosis of PH-CCA. One further patient had a final diagnosis of an intraductal papillary neoplasm of the biliary tree (IPNB) with high-grade dysplasia but no invasive cancer. Eleven patients (36%) received chemotherapy after surgery. The median (95% CI) time to recurrence was 14 (7-31) months. The median survival was 25 (18-upper limit not reached) months. Conclusion: This cohort of 32 patients undergoing attempted resection for PH-CCA without the use of staging laparoscopy in the work-up algorithm indicates that with careful attention to patient fitness and cross-sectional and interventional radiologic/endoscopic imaging, a very low non-therapeutic laparotomy rate of 3% can be achieved and sustained.


Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review.
Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified around 108 references. In this study, 68 studies were accepted for further screening, and met all our inclusion criteria [in English, full text, chemopreventive and chemotherapeutic effects of Camellia sinensis and dated mainly from the year 1999 to 2016. The search terms were Camellia sinensis, chemopreventive, chemotherapeutic properties, pharmacological effects. The result of this study suggested that the catechin available in Camellia sinensis has properties which can prevent and treat breast cancer. It has also been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. It was found that increased Camellia sinensis consumption may lower the risk of breast cancer. Camellia sinensis intake was shown to reduce the risk of breast cancer incidence. In addition, potential breast cancer chemopreventive effect of Camellia sinensis both in vivo and in vitro was highly confirmed. However, the evidence of low effect and no effect was observed. More clinical trial studies are needed to prove its anti-breast cancer activity decisively. Camellia sinensis is broadly utilized as a part of customary medication since antiquated time because of its cost adequacy, and fewer reaction properties. The studies demonstrated anti-breast cancer activity of Camellia sinensis and its component by adjusting cell signaling pathways such as angiogenesis, apoptosis, and transcription factor. Furthermore, Camellia sinensis and its chemical compound was shown to be extremely useful in the development of novel anticancer medications.


Study of indentation of a sample equine bone using finite element simulation and single cycle reference point indentation.
In an attempt to study the mechanical behavior of bone under indentation, methods of analyses and experimental validations have been developed, with a selected test material. The test material chosen is from an equine cortical bone. Stress-strain relationships are first obtained from conventional mechanical property tests. A finite element simulation procedure is developed for indentation analyses. The simulation results are experimentally validated by determining (1) the maximum depth of indentation with a single cycle type of reference point indentation, and (2) the profile and depth of the unloaded, permanent indentation with atomic force microscopy. The advantage of incorporating in the simulation a yield criterion calibrated by tested mechanical properties, with different values in tension and compression, is demonstrated. In addition, the benefit of including damage through a reduction in Young's modulus is shown in predicting the permanent indentation after unloading and recovery. The expected differences in response between two indenter tips with different sharpness are predicted and experimentally observed. Results show predicted indentation depths agree with experimental data. Thus, finite element simulation methods with experimental validation, and with damage approximation by a reduction of Young's modulus, may provide a good approach for analysis of indentation of cortical bone. These methods reveal that multiple factors affect measured indentation depth and that the shape of the permanent indentation contains useful information about bone material properties. Only further work can determine if these methods or extensions to these methods can give useful insights into bone pathology, for example the bone fragility of thoroughbred racehorses.


An air quality forecasting system in Beijing--application to the study of dust storm events in China in May 2008.
An air pollution forecast system, ARIA Regional, was implemented in 2007-2008 at the Beijing Municipality Environmental Monitoring Center, providing daily forecast of main pollutant concentrations. The chemistry-transport model CHIMERE was coupled with the dust emission model MB95 for restituting dust storm events in springtime so as to improve forecast results. Dust storm events were sporadic but could be extremely intense and then control air quality indexes close to the source areas but also far in the Beijing area. A dust episode having occurred at the end of May 2008 was analyzed in this article, and its impact of particulate matter on the Chinese air pollution index (API) was evaluated. Following our estimation, about 23 Tg of dust were emitted from source areas in Mongolia and in the Inner Mongolia of China, transporting towards southeast. This episode of dust storm influenced a large part of North China and East China, and also South Korea. The model result was then evaluated using satellite observations and in situ data. The simulated daily concentrations of total suspended particulate at 6:00 UTC had a similar spatial pattern with respect to OMI satellite aerosol index. Temporal evolution of dust plume was evaluated by comparing dust aerosol optical depth (AOD) calculated from the simulations with AOD derived from MODIS satellite products. Finally, the comparison of reported Chinese API in Beijing with API calculated from the simulation including dust emissions had showed the significant improvement of the model results taking into account mineral dust correctly.


Evaluation of forensic cases presented to the pediatric emergency department.
Child forensic cases constitute an essential part of emergency presentations. The most crucial point is that the correct planning of protective and preventive activities depends on the correct analysis of the problem; therefore, there is a need for studies on childhood forensic cases. This study aimed to obtain data on the etiological characteristics of forensic cases presented to the pediatric emergency department. We believe that the collected data will guide the social measures in preventing forensic cases. This retrospective study consists of forensic cases aged from 1 month to 18 years and presented to the pediatric emergency service of Adana City Training and Research Hospital between January 1, 2018, and December 31, 2019. The general forensic examination report of the cases was surveyed. For this study, 6577 general forensic examination reports were surveyed. 40% of the patients were females, and 60% were males. Traffic accidents were the most common (35.1%) cause of the emergency presentation, which was followed by assault (16.5%), fall from height (9.2%), accidental drug-caustic corrosive substance intake (7.8%), early pregnancy (7.4%), blunt or sharp force injuries (6.3%), electrical burn injuries (5.7%), suicide (5.1%), carbon monoxide-food poisoning (2.7%), and others that consisted of work accident, firearm injury, substance ingestion, suffocation, animal attack, sudden death, and missing child (4.2%). This most extensive study with 6577 cases has several important implications. First of all, traffic accidents continue to be an important public health problem today. Second, cases presented to the emergency department due to assault and blunt or sharp force injuries constitute an important part of forensic cases, and children who are driven to violence and crime in childhood are a situation that requires immediate action. Our third yet most important result is that early pregnancy is a much ignored social problem despite its importance.


Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping.
We used the cerebellum as a model to study the morphogenetic and cellular processes underlying the formation of elaborate brain structures from a simple neural tube, using an inducible genetic fate mapping approach in mouse. We demonstrate how a 90 degrees rotation between embryonic days 9 and 12 converts the rostral-caudal axis of dorsal rhombomere 1 into the medial-lateral axis of the wing-like bilateral cerebellar primordium. With the appropriate use of promoters, we marked specific medial-lateral domains of the cerebellar primordium and derived a positional fate map of the murine cerebellum. We show that the adult medial cerebellum is produced by expansion, rather than fusion, of the thin medial primordium. Furthermore, ventricular-derived cells maintain their original medial-lateral coordinates into the adult, whereas rhombic lip-derived granule cells undergo lateral to medial posterior transverse migrations during foliation. Thus, we show that progressive changes in the axes of the cerebellum underlie its genesis.


Radiolabeled probes targeting hypoxia-inducible factor-1-active tumor microenvironments.
Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1) expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α), which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of (18)F-FDG or (18)F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.


Exercise in the prevention and treatment of cancer. An update.
Physical activity potentially encourages a healthy lifestyle and it could have a more direct preventive effect on certain forms of carcinogenesis (for instance, by speeding gastrointestinal transit, or by moderating sex hormone levels). However, there are also potential negative effects, particularly an excessive exposure to ultraviolet light in certain water sports. The many types of neoplasm and the equally varied sources of physical activity militate against finding any simple relationship between the risk of malignancy and the individual's physical activity history. Nevertheless, evidence that physical activity protects against certain forms of cancer can be deduced from studies of experimental animals, former athletes, people employed in active occupations, and those with an active recreational lifestyle. Many occupational surveys and a number of studies of recreational activity show an association between sedentary living and a risk of colon cancer, both in men and in women. Moreover, an application of Bradford Hill's criteria gives some support to the causal nature of the association. More limited data suggest that a history of active leisure is associated with a reduced risk of all-cause cancer and in women of breast and reproductive system cancers. The last observation must still be reconciled with an apparent increase in the risk of prostatic cancer in active men. Since moderate exercise elevates mood and helps to conserve lean tissue, it may finally be a helpful component of treatment after a neoplasm has been diagnosed.


Supercontinuum generation with optical vortices.
We employ an optical vortex beam for the generation of femtosecond supercontinuum in a solid state medium. We demonstrate that the continuum generation process is initiated by the filamentation of the vortex, resulting in a spatially divergent continuum. Despite the strong self-focusing and the formation of multiple hot-spots along the vortex ring, the singularity is preserved in both the near- and far-fields.


Burden of disease associated with alcohol use disorders in the United States.
Alcohol use disorders (AUD) have long been considered to be some of the most disabling mental disorders; however, empirical data on the burden of disease associated with AUD have been sparse. The objective of this article is to quantify the burden of disease (in disability-adjusted life years [DALYs] lost), deaths, years of life lost due to premature mortality (YLL), and years of life lost due to disability (YLD) associated with AUD for the United States in 2005. Statistical modeling was based on epidemiological indicators derived from the National Epidemiologic Survey on Alcohol and Related Conditions. Formal consistency analyses were applied. Risk relations were taken from recent meta-analyses and the disability weights from the burden of disease study of the National Institutes of Health. Monte Carlo simulations were used to derive confidence intervals. All analyses were performed by sex and age. Sensitivity analyses were undertaken on key indicators. In the United States in 2005, 65,000 deaths, 1,152,000 YLL, 2,443,000 YLD, and 3,595,000 DALYs were associated with AUD. For individuals 18 years of age and older, AUD were associated with 3% of all deaths (5% for men and 1% for women), and 5% of all YLL (7% for men and 2% for women). The majority of the burden of disease associated with AUD stemmed from YLD, which accounted for 68% of DALYs associated with AUD (66% for men and 74% for women). The youngest age group had the largest proportion of DALYs associated with AUD stemming from YLD. Using data from a large representative survey (checked for consistency) and by combining these data with the best available evidence, we found that AUD were associated with a larger burden of disease than previously estimated. To reduce this disease burden, implementation of prevention interventions and expansion of treatment are necessary.


Surgical repositioning of a developing maxillary central incisor. A case report.
A traumatic injury to the primary dentition can cause damage to the germ of the permanent successor. As a clinical consequence a dilaceration with root deformation, malpositioning and disturbances of eruption can occur. Surgical repositioning of such a dislocated crown of a developing tooth can be a treatment option. A four year old patient was referred to our clinic because of a mobile upper primary central incisor and a radiographically visible displaced dental crown. Her history revealed a traumatic dental injury one year ago. Radiologic examination confirmed an inflammatory root resorption on tooth 61 and a dislocation of the developing tooth 21. In order to avoid further displacement due to the inflammation, 61 was extracted at the first appointment. A radiographic image 7 months later showed no improvement in the malposition of tooth 21. Therefore tooth 21 was surgically repositioned into its correct position. Follow-up over 3 years confirmed a continued root development and a full eruption of 21 in its correct position. Early diagnosis and early treatment of a dislocated permanent tooth germ is essential to allow a favorable outcome. Surgical repositioning can be successful in avoiding later malpositioning of the permanent teeth.


NMR and TRLFS studies of Ln(iii) and An(iii) C5-BPP complexes.
C5-BPP is a highly efficient N-donor ligand for the separation of trivalent actinides, An(iii), from trivalent lanthanides, Ln(iii). The molecular origin of the selectivity of C5-BPP and many other N-donor ligands of the BTP-type is still not entirely understood. We present here the first NMR studies on C5-BPP Ln(iii) and An(iii) complexes. C5-BPP is synthesized with 10% 15N labeling and characterized by NMR and LIFDI-MS methods. 15N NMR spectroscopy gives a detailed insight into the bonding of C5-BPP with lanthanides and Am(iii) as a representative for trivalent actinide cations, revealing significant differences in 15N chemical shift for coordinating nitrogen atoms compared to Ln(iii) complexes. The temperature dependence of NMR chemical shifts observed for the Am(iii) complex indicates a weak paramagnetism. This as well as the observed large chemical shift for coordinating nitrogen atoms show that metal-ligand bonding in Am(C5-BPP)3 has a larger share of covalence than in lanthanide complexes, confirming earlier studies. The Am(C5-BPP)3 NMR sample is furthermore spiked with Cm(iii) and characterized by time-resolved laser fluorescence spectroscopy (TRLFS), yielding important information on the speciation of trace amounts of minor complex species.


Aerodynamic sound generation of flapping wing.
The unsteady flow and acoustic characteristics of the flapping wing are numerically investigated for a two-dimensional model of Bombus terrestris bumblebee at hovering and forward flight conditions. The Reynolds number Re, based on the maximum translational velocity of the wing and the chord length, is 8800 and the Mach number M is 0.0485. The computational results show that the flapping wing sound is generated by two different sound generation mechanisms. A primary dipole tone is generated at wing beat frequency by the transverse motion of the wing, while other higher frequency dipole tones are produced via vortex edge scattering during a tangential motion. It is also found that the primary tone is directional because of the torsional angle in wing motion. These features are only distinct for hovering, while in forward flight condition, the wing-vortex interaction becomes more prominent due to the free stream effect. Thereby, the sound pressure level spectrum is more broadband at higher frequencies and the frequency compositions become similar in all directions.


Transcriptomic changes during regeneration of the central nervous system in an echinoderm.
Echinoderms are emerging as important models in regenerative biology. Significant amount of data are available on cellular mechanisms of post-traumatic repair in these animals, whereas studies of gene expression are rare. In this study, we employ high-throughput sequencing to analyze the transcriptome of the normal and regenerating radial nerve cord (a homolog of the chordate neural tube), in the sea cucumber Holothuria glaberrima. Our de novo assembly yielded 70,173 contigs, of which 24,324 showed significant similarity to known protein-coding sequences. Expression profiling revealed large-scale changes in gene expression (4,023 and 3,257 up-regulated and down-regulated transcripts, respectively) associated with regeneration. Functional analysis of sets of differentially expressed genes suggested that among the most extensively over-represented pathways were those involved in the extracellular matrix (ECM) remodeling and ECM-cell interactions, indicating a key role of the ECM in regeneration. We also searched the sea cucumber transcriptome for homologs of factors known to be involved in acquisition and/or control of pluripotency. We identified eleven genes that were expressed both in the normal and regenerating tissues. Of these, only Myc was present at significantly higher levels in regeneration, whereas the expression of Bmi-1 was significantly reduced. We also sought to get insight into which transcription factors may operate at the top of the regulatory hierarchy to control gene expression in regeneration. Our analysis yielded eleven putative transcription factors, which constitute good candidates for further functional studies. The identified candidate transcription factors included not only known regeneration-related genes, but also factors not previously implicated as regulators of post-traumatic tissue regrowth. Functional annotation also suggested that one of the possible adaptations contributing to fast and efficient neural regeneration in echinoderms may be related to suppression of excitotoxicity. Our transcriptomic analysis corroborates existing data on cellular mechanisms implicated in regeneration in sea cucumbers. More importantly, however, it also illuminates new aspects of echinoderm regeneration, which have been scarcely studied or overlooked altogether. The most significant outcome of the present work is that it lays out a roadmap for future studies of regulatory mechanisms by providing a list of key candidate genes for functional analysis.


Evaluation of pro-carboxypeptidase A and carboxypeptidase A as serologic markers for adenocarcinoma of the pancreas.
A serological marker for pancreatic cancer may allow for early detection and potentially more effective treatments. Pro-carboxypeptidase A (pro-CPA) is produced exclusively in the pancreas and converted to its active form, CPA, in the intestinal lumen. We hypothesized that alterations in serum pro-CPA and/or CPA may be useful as a diagnostic test for pancreatic cancer. Serum samples obtained from 34 patients with pancreatic adenocarcinoma prior to surgical intervention and 64 control patients were assayed for pro-CPA and CPA. A variety of statistical methods was used to evaluate the utility of these measurements individually and in combination to classify the samples with respect to the presence or absence of pancreatic adenocarcinoma. Because of positive skewing of the data in some populations, transformation of the data to natural logarithmic scales was used and resulted in normal distributions. All pancreatic cancer patients had ln(CPA) levels within or below the normal range defined as two standard deviations from the control group mean (-2.714+/-0.413). Ln(pro-CPA) levels in 24 of 34 cancer patients were outside the normal range of the control group (0.306+/-0.33). Pancreatic cancer patients with ln pro-CPA values within the control range had low ln CPA, advanced stage and/or evidence of pancreatic insufficiency. While each of these individual values (ln pro-CPA or ln CPA) does not adequately separate all control from cancer patients, a bivariate classification rule is presented that uses both ln pro-CPA and ln CPA simultaneously to predict the presence of pancreatic cancer with a sensitivity of 91% and a specificity of 95%. The data presented suggest that abnormalities in serum pro-CPA and CPA levels are associated with the presence of pancreatic cancer.


Hidden hearing loss and endbulbs of Held: Evidence for central pathology before detection of ABR threshold increases.
Reductions in sound-evoked activity in the auditory nerve due to hearing loss have been shown to cause pathological changes in central auditory structures. Hearing loss due strictly to the aging process are less well documented. In this study of CBA/CaH mice, we provide evidence for age-related pathology in the endbulb of Held, a large axosomatic ending arising from myelinated auditory nerve fibers. Endbulbs are known to be involved in the processing of temporal cues used for sound localization and speech comprehension. Hearing thresholds as measured by auditory brainstem response (ABR) thresholds remained stable up to one year, whereas suprathreshold amplitudes of early ABR waves decreased by up to 50% in older mice, similar to that reported for age-related cochlear synaptopathy (Sergeyenko et al., 2013). The reduction of ABR response magnitude with age correlated closely in time with the gradual atrophy of endbulbs of Held, and is consistent with the hypothesis that endbulb integrity is dependent upon normal levels of spike activity in the auditory nerve. These results indicate that central auditory pathologies emerge as consequence of so-called "hidden" hearing loss and suggest that such brain changes require consideration when devising therapeutic interventions.


Early Development of Locomotor Patterns and Motor Control in Very Young Children at High Risk of Cerebral Palsy, a Longitudinal Case Series.
The first years of life might be critical for encouraging independent walking in children with cerebral palsy (CP). We sought to identify mechanisms that may underlie the impaired development of walking in three young children with early brain lesions, at high risk of CP, via comprehensive instrumented longitudinal assessments of locomotor patterns and muscle activation during walking. We followed three children (P1-P3) with early brain lesions, at high risk of CP, during five consecutive gait analysis sessions covering a period of 1 to 2 years, starting before the onset of independent walking, and including the session during the first independent steps. In the course of the study, P1 did not develop CP, P2 was diagnosed with unilateral and P3 with bilateral CP. We monitored the early development of locomotor patterns over time via spatiotemporal gait parameters, intersegmental coordination (estimated via principal component analysis), electromyography activity, and muscle synergies (determined from 11 bilateral muscles via nonnegative matrix factorization). P1 and P2 started to walk independently at the corrected age of 14 and 22 months, respectively. In both of them, spatiotemporal gait parameters, intersegmental coordination, muscle activation patterns, and muscle synergy structure changed from supported to independent walking, although to a lesser extent when unilateral CP was diagnosed (P2), especially for the most affected leg. The child with bilateral CP (P3) did not develop independent walking, and all the parameters did not change over time. Our exploratory longitudinal study revealed differences in maturation of locomotor patterns between children with divergent developmental trajectories. We succeeded in identifying mechanisms that may underlie impaired walking development in very young children at high risk of CP. When verified in larger sample sizes, our approach may be considered a means to improve prognosis and to pinpoint possible targets for early intervention.


Farmers' willingness to pay for foot and mouth disease vaccine in different cattle production systems in Amhara region of Ethiopia.
Although foot and mouth disease (FMD) is endemic in Ethiopia, use of vaccines to control the disease has been practiced sparingly. This is due to perceived high cost of good quality FMD vaccine, and consequently limited availability of the vaccine in the market. This study was conducted to assess farmers' willingness to pay (WTP) for a quality FMD vaccine and identify factors that could potentially influence their WTP in Amhara region of Ethiopia. A total of 398 farmers from four districts that represent the mixed crop-livestock and market oriented production systems were enrolled for the study. The WTP was estimated using contingent valuation method with a double-bound dichotomous choice bid design. Interval regression analysis was used to estimate mean WTP and identify factors that influence it. The results showed that the mean WTP of all farmers was Ethiopian Birr (ETB) 58.23 (95% CI: 56.20-60.26)/annual dose. It was ETB 75.23 (95% CI: 72. 97-74.49) for market oriented farmers and ETB 42.6 (95%CI: 41.24-43.96) for mixed crop livestock farmers. Willingness to pay for the vaccine was significantly higher for farmers in market oriented system than in mixed crop livestock system. It was also significantly higher for farmers whose main livelihood is livestock than those whose main livelihood is other than livestock, and for farmers who keep exotic breed cattle and their crosses than those who keep only local cattle breeds. Willingness to pay significantly increased with increase in FMD impact perception and vaccine knowledge scores of farmers. The high mean WTP estimates showed that farmers are enthusiastic about using the FMD vaccine. Market-oriented farmers with higher willingness to pay may be more likely to pay full cost if official FMD vaccination is planned in the country than mixed crop livestock farmers. Animal health extension about livestock diseases impact and vaccines has a potential to increase farmers' uptake of vaccines for disease control.


Identification and characterization of type A endothelin receptors in MMQ cells.
Recently the identification of endothelin (ET) receptors and ET in the pituitary gland has induced much interest in studying the potential role of ET in neuroendocrine regulation. MMQ, isolated from rat pituitary, is a prolactin-secreting cell line. Similar to primary pituitary cells, the secretory response in MMQ cells is regulated by calcium and cAMP. In this report, by combining radioligand binding, cross-linking, and reverse transcription-polymerase chain reaction (RT-PCR) techniques, we characterized the properties of ET receptors in MMQ cells. 125I-ET-1 bound to membranes prepared from MMQ cells in a time-dependent manner, reaching a plateau at 150 min at 25 degrees. 125I-ET-1 binding was inhibited by ET-1 with an IC50 value of 0.17 nM but was only partially (approximately 60%) inhibited by 1 microM ET-3. BQ123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) and FR139317 (cC6N-L-Leu-D-Trp-Me-D-2Pya-OH), two antagonists that are selective for the ETA receptor, inhibited 125I-ET-1 binding with IC50 values of 5 nM and 0.9 nM, respectively. RT-PCR detected mRNA for the ETA receptor but not the ETB receptor. RT-PCR detected mRNA for both ETA and ETB receptors in control experiments using rat kidney RNA. 125I-ET-1 binding was saturable, reaching a plateau at 0.1 nM. Scatchard analysis of the data from saturation studies yielded a straight line, with Bmax and Kd values of 0.11 pmol/mg and 0.038 nM, respectively. The number of receptors was 6.6 x 10(10) sites/mg of protein or 13,200 sites/cell. Cross-linking studies using bis(sulfosuccinimidyl)suberate revealed an apparent molecular mass of 65 kDa for the ET receptor. Labeling of the 65-kDa protein was abolished by ET-1, BQ123, or FR139317 at 0.1 microM. ET-1 stimulated the formation of total inositol phosphates in a dose-dependent manner, with an EC50 of 0.1 nM. The phosphatidylinositol hydrolysis response was also inhibited by BQ123 and FR139317. We conclude that MMQ cells express the ETA receptor, which is coupled to phosphatidylinositol hydrolysis. MMQ cells may be useful for elucidating the mechanisms through which ET exerts its regulatory effects on pituitary cells.


Factors affecting decisions to seek treatment for sick children in Kerala, India.
The purpose of this study was to measure the effects of social and economic variables, disease-related variables, and child gender on the decisions of parents in Kerala, India, to seek care for their children and on their choice of providers in the allopathic vs. the alternative system. A case-control analysis was done using data from the Kerala section of the 1996 Indian National Family Health Survey, a cross-sectional survey of a probability sample of households conducted by trained interviewers with a close-ended questionnaire. Of the 469 children who were eligible for this study because they had at least one common symptom suggestive of acute respiratory illness or diarrhea during the 2 weeks before the interview, 78 (17%) did not receive medical care, while the remaining 391 (83%) received medical care. Of the 391 children who received medical care, 342 (88%) received allopathic medical care, and 48 (12%) received alternative medical care. In multivariable analyses, parents chose not to seek medical care for their children significantly more often when the illness was mild, the child had a specific diagnosis, the mother had previously made fewer antenatal visits, and the family had a higher economic status. When parents sought medical care for their children, care was sought significantly more often in the alternative provider system when the child was a boy, the family lived in a rural area, and the family had a lower social class. We conclude that, in Kerala, disease severity and economic status predict whether children with acute respiratory infection or diarrhea are taken to medical providers. In contrast, most studies of this issue carried out in other populations have identified economic status as the primary predictor of medical system utilization. Also in Kerala, the gender of the child did not influence whether or not the child was taken for treatment but did influence whether care was sought in the alternative or the allopathic system.


Lens Position Parameters as Predictors of Intraocular Pressure Reduction After Cataract Surgery in Glaucomatous Versus Nonglaucomatous Eyes.
To evaluate the relationship between lens position parameters and intraocular pressure (IOP) reduction after cataract surgery in patients with primary open-angle glaucoma (POAG) and in nonglaucomatous patients. The main outcomes of this prospective study were percent and absolute IOP change, which were calculated using the preoperative IOP and the IOP 4 months after cataract surgery in POAG and nonglaucomatous eyes. Lens position (LP), defined as anterior chamber depth (ACD) + one-half lens thickness (LT), was assessed preoperatively using parameters from optical biometry. Preoperative IOP, axial length (AL), ACD, LT, relative lens position (RLP), and the ratio of preoperative IOP to ACD (PD ratio) were also evaluated as potential predictors of IOP change. Four months postoperatively, the average IOP reduction was 2.80 ± 3.83 mm Hg (15.79%) from the preoperative mean of 14.73 ± 2.89 mm Hg for nonglaucomatous eyes. The average IOP reduction was 2.66 ± 2.07 mm Hg (16.98%) from the preoperative mean of 14.86 ± 2.97 mm Hg for POAG eyes. Preoperative IOP, sex, AL, ACD, PD ratio, and LP predicted IOP change in nonglaucomatous eyes. Preoperative IOP and PD ratio predicted IOP change in POAG eyes. Intraocular pressure reduction after phacoemulsification cataract surgery in nonglaucomatous eyes is significantly greater in more anteriorly positioned lenses. Though it did not reach statistical significance in patients with glaucoma, the association of LP with IOP reduction is in the same direction as in nonglaucomatous patients where smaller LP appears to predict greater IOP reduction. Lens position is a simple, easily calculable, accurate, and widely available parameter, which clinicians can potentially utilize in managing glaucoma.


Relations of mindfulness facets with psychological symptoms among individuals with a diagnosis of obsessive-compulsive disorder, major depressive disorder, or borderline personality disorder.
To explore differences in mindfulness facets among patients with a diagnosis of either obsessive-compulsive disorder (OCD), major depressive disorder (MDD), or borderline personality disorder (BPD), and healthy controls (HC), and their associations with clinical features. One hundred and fifty-three patients and 50 HC underwent a clinical assessment including measures of mindfulness (Five Facets Mindfulness Questionnaire - FFMQ), psychopathological symptoms (Symptom Check List-90-R), dissociation (Dissociative Experience Scale), alexithymia (Alexithymia Scale 20), and depression (Beck Depression Inventory-II). Analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were performed to assess differences in mindfulness scores and their associations with clinical features. The three diagnostic groups scored lower on all mindfulness facets (apart from FFMQobserving) compared to the HC group. OCD group had a significant higher FFMQ total score (FFMQ-TS) and FFMQacting with awareness compared to the BPD group, and scored higher on FFMQdescribing compared to BPD and MDD groups. The scores in non-judging facet were significantly lower in all the three diagnostic groups compared to the HC group. Interestingly, higher FFMQ-TS was inversely related to all psychological measures, regardless of diagnostic group. Deficits in mindfulness skills were present in all diagnostic groups. Furthermore, we found disease-specific relationships between some mindfulness facets and specific psychological variables. Clinical implications are discussed. The study showed deficits in mindfulness scores in all diagnostic groups compared to a healthy control group. Overall, mindfulness construct has a significantly negative association with indexes of global distress, dissociative symptoms, alexithymia, and depression. Mindfulness-based interventions in clinical settings should take into account different patterns of mindfulness skills and their impact on disease-specific maladaptive cognitive strategies or symptomatology.


[Developmental changes in judgment of weights addition].
As weight is invisible, some judgmental criteria are needed in judging weight. An experiment was carried out using the second, fourth, sixth, eighth graders and college students to reveal (1) what weights positions make subjects more errors in judgment of weights addition and (2) what relationships will be found between the judgments and judgmental criteria. Subjects were engaged in the tasks to judge weights addition in two conditions, height of weights and relative positions, and were asked the judgmental criteria in two situations, visual exteroceptive and realistic proprioceptive situations. Results showed clearly the developmental changes. The fourth graders dominantly produced errors in height of weights conditions and tended to depend on the criteria in realistic situations. In the contrast to this, the eighth graders committed errors in relative differences of weights positions and depended on the criteria in visual situations as well as realistic ones. Sex differences were also observed in terms of criteria. No relations between the judgments and judgmental criteria was found in girls' judgments of weights additions.


Defining and Delimitating Telemedicine and Related Terms - An Ontology-Based Classification.
The way health care is delivered changes continuously and is increasingly supported by digital technologies, such as telemedicine. Many terms in that context exist, which are not defined consistently and therefore used ambiguously. This makes it difficult to assess the evidence base. Ontologies bring structure and clarity to the discourse around telemedicine and related terms. We use this tool to provide definitions of relevant terms and show their interrelations. The results provided will be applied to different case studies to show their applicability. We aim to provide a more evidence-based understanding of relevant terms in digital health.


Implementing radical cure diagnostics for malaria: user perspectives on G6PD testing in Bangladesh.
The radical cure of Plasmodium vivax requires treatment with an 8-aminoquinoline drug, such as primaquine and tafenoquine, to eradicate liver hypnozoite stages, which can reactivate to cause relapsing infections. Safe treatment regimens require prior screening of patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency to avoid potential life-threatening drug induced haemolysis. Testing is rarely available in malaria endemic countries, but will be needed to support routine use of radical cure. This study investigates end-user perspectives in Bangladesh on the introduction of a quantitative G6PD test (SD Biosensor STANDARD™ G6PD analyser) to support malaria elimination. The perspectives of users on the SD Biosensor test were analysed using semi-structured interviews and focus group discussions with health care providers and malaria programme officers in Bangladesh. Key emerging themes regarding the feasibility of introducing this test into routine practice, including perceived barriers, were analysed. In total 63 participants were interviewed. Participants emphasized the life-saving potential of the biosensor, but raised concerns including the impact of limited staff time, high workload and some technical aspects of the device. Participants highlighted that there are both too few and too many P. vivax patients to implement G6PD testing owing to challenges of funding, workload and complex testing infrastructure. Implementing the biosensor would require flexibility and improvisation to deal with remote sites, overcoming a low index of suspicion and mutual interplay of declining patient numbers and reluctance to test. This approach would generate new forms of evidence to justify introduction in policy and carefully consider questions of deployment given declining patient numbers. The results of the study show that, in an elimination context, the importance of malaria needs to be maintained for both policy makers and the affected communities, in this case by ensuring P. vivax, PQ treatment, and G6PD deficiency remain visible. Availability of new technologies, such as the biosensor, will fuel ongoing debates about priorities for allocating resources that must be adapted to a constantly evolving target. Technical and logistical concerns regarding the biosensor should be addressed by future product designs, adequate training, strengthened supply chains, and careful planning of communication, advocacy and staff interactions at all health system levels.