Optimizing Ballistic Imaging Operations.
Ballistic imaging systems can help solve crimes by comparing images of cartridge cases, which are recovered from a crime scene or test-fired from a gun, to a database of images obtained from past crime scenes. Many U.S. municipalities lack the resources to process all of their cartridge cases. Using data from Stockton, CA, we analyze two problems: how to allocate limited capacity to maximize the number of cartridge cases that generate at least one hit, and how to prioritize the cartridge cases that are processed to maximize the usefulness (i.e., obtained before the corresponding criminal case is closed) of hits. The number of hits can be significantly increased by prioritizing crime scene evidence over test-fires, and by ranking calibers by their hit probability and processing only the higher ranking calibers. We also estimate that last-come first-served increases the proportion of hits that are useful by only 0.05 relative to first-come first-served.


A computer-operated following ellipsometer.
This paper describes the construction and performance of a computer-operated following ellipsometer. By modifying a conventional ellipsometer and operating it with a process control computer, the polarizer and analyzer null positions can he located in about one second with a resolution of 0.01 degrees . This instrument has been used successfully for in situ studies of the buildup and removal of thin anodic oxide films. As the growth of a film is monitored, the computer also plots the null positions of an X-Y recorder and stores all the experimental data for later printing, punching on cards, or replotting along with theoretical curves.


Post-cataract surgery cluster endophthalmitis due to multidrug-resistant Pseudomonas aeruginosa: A retrospective cohort study of six clusters.
To analyze clinical presentations, antibiotic susceptibility, and visual outcomes in six clusters of post cataract surgery endophthalmitis caused due to multidrug-resistant Pseudomonas aeruginosa (MDR-PA). This was a hospital-based retrospective cohort study. Our study comprised sixty-two patients from six nonconsecutive clusters of post cataract surgery endophthalmitis caused by MDR-PA referred to our tertiary eye care institute. Demographic details, best-corrected visual acuity (BCVA), clinical features, microbiological findings, and patient management were reviewed. The interval between onset of symptoms and presentation ranged from 1 to 7 (mean: 4.61 and median: 5) days. The presenting BCVA was no light perception in 17 (27.4%) eyes, light perception in 35 (56.4%) eyes, and hand movement or better in 10 (16.1%) eyes. All patients had hypopyon and vitreous exudates. Corneal infiltrates were noted in 40 (64.5%) eyes. Panophthalmitis was diagnosed in 20 (32.2%) eyes. The surgical intervention included intraocular antibiotics (IOAB) in 8 (12.9%) eyes, pars plana vitrectomy with IOAB in 26 (41.9%) eyes, and evisceration in 23 (37.09%) eyes. At 6 weeks, BCVA of 20/200 or better was achieved in 9 (14.5%) eyes. Pseudomonas aeruginosa was least resistant to colistin (8.3%), piperacillin (31.8%), and imipenem (36.1%). Ceftriaxone and ceftazidime resistance was seen in 80.5% and 70% isolates, respectively. Cluster endophthalmitis due to MDR-PA has poor visual outcomes with high rates of evisceration. In the setting of cluster endophthalmitis where MDR-PA is the most common etiology, piperacillin or imipenem can be the first drug of choice for empirical intravitreal injection for gram-negative coverage while awaiting the drug susceptibility report.


Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity.
HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two probe FISH interphase analysis is inadequate and results interpreted using the HER2/CEP17 ratio should be reported "with caution" when the presence of centromeric amplification or monosomy is suspected by FISH signal gains or losses. The presence of these pericentromeric copy number changes may result in artificial skewing of the HER2/CEP17 ratio towards false negative or false positive results in breast cancer with chromosome 17 complexity. Full genomic analysis should be considered in all cases with complex chromosome 17 aneusomy as these cases are likely to have genome-wide instability, amplifications, and a poor prognosis.


Improvement of the oblique-incidence optical interferometric system to measure tooth flanks of involute helical gears.
We put forward a plan of improving the oblique-incidence optical interferometric system applied in the measurement of tooth flanks of an involute spur gear in order to expand its capability to measure an involute helical gear. On the basis of the features of an involute helical tooth flank, we discuss how to realize the parallelism between the optical axis of the object arm of the optical system and the straight lines constructing the involute helical tooth flank. This parallelism helps the optical system produce an interference fringe pattern as clear as the one of an involute spur gear [Appl. Opt.49, 6409 (2010).]. A numerical simulation is then performed to examine the correctness of the improvement. During simulating, we unify the equation of difference tooth flanks by means of importing two parameters in relation to the left or right side of a tooth flank and the helical direction of teeth, respectively. Finally, the actual experiment is fulfilled through the real optical system built on an optical table. The simulation and experiment results verify the correctness and feasibility of the proposed improvement.


Evidence-based causation in toxicology: A 10-year retrospective.
We introduced Evidence-based Toxicology (EBT) in 2005 to address the disparities that exist between the various Weight-of-Evidence (WOE) methods typically applied in the regulatory hazard decision-making arena and urged toxicologists to adopt the evidence-based guidelines long-utilized in medicine (i.e., Evidence-Based Medicine or EBM). This review of the activities leading to the adoption of evidence-based methods and EBT during the last decade demonstrates how fundamental concepts that form EBT, such as the use of systematic reviews to capture and consider all available information, are improving toxicological evaluations performed by various groups and agencies. We reiterate how the EBT framework, a process that provides a method for performing human chemical causation analyses in an objective, transparent and reproducible manner, differs significantly from past and current regulatory WOE approaches. We also discuss why the uncertainties associated with regulatory WOE schemes lead to a definition of the term "risk" that contains unquantifiable uncertainties not present in this term as it is used in epidemiology and medicine. We believe this distinctly different meaning of "risk" should be clearly conveyed to those not familiar with this difference (e.g., the lay public), when theoretical/nomologic risks associated with chemical-induced toxicities are presented outside of regulatory and related scientific parlance.


Is progression of coronary artery calcification influenced by modality of renal replacement therapy? A systematic review.
Progression of coronary artery calcification is an important marker for cardiovascular morbidity in end-stage renal disease patients. Therefore, we reviewed the evidence on coronary artery calcification progression in different renal replacement therapies. MEDLINE (PubMed), Embase and TRIP databases were searched from 1999 - 2016. Additionally, bibliographies were searched by hand and citation tracking of key publications was performed. Prospective studies were included that examined coronary artery calcification with two or more multislice computed tomography scans ≥6 months apart in patients 18-75 years old receiving any renal replacement therapy, including kidney transplantation. Reporting of separate scores for different modalities was required. Two researchers extracted data independently with pilot-tested forms and assessed the risk of bias using a validated tool. We identified 29 eligible studies that assessed coronary artery calcification progression in end-stage renal disease patients, of which 19 studies evaluated haemodialysis and 8 kidney transplantation. Evidence on progression in peritoneal dialysis (three studies) and nocturnal haemodialysis (one study) was limited. Meta-analysis was not possible due to diverse reporting methods of coronary artery calcification scores and definitions of progression. Median coronary artery calcification scores were considerably higher in haemodialysis cohorts at baseline, presumably due to a generally higher age and dialysis vintage. Median coronary artery calcification progressed universally. Visual inspection suggested the least progression in kidney transplant recipients. There is insufficient evidence to compare the influence of renal replacement therapies on coronary artery calcification progression. We advocate the adoption of a standardized reporting method of coronary artery calcification progression.


Polymer crystallization under nano-confinement of droplets studied by molecular simulations.
Fabrication of polymer nano-crystals proceeds usually through hierarchical ordering of the different-scale structures. Nano-scale patterns are produced first, which serve as a spatial template for subsequent polymer crystallization under nano-confinement. We begin with a survey of the effects of nano-confinement on polymer crystallization, mainly on the basis of the knowledge obtained from molecular simulations. After that, we report dynamic Monte Carlo simulations of polymer crystallization confined in nano-droplets. We observed that the shape of droplets on a solid substrate appears as a pancake, and both initiation and development of crystallization are depressed with the decrease of droplet size. Surface-induced crystal nucleation guides the dominant edge-on crystal orientation at high temperatures; however, its contribution to nucleation rates is not much greater than crystal nucleation in the volume of the droplet. At low temperatures, edge-on crystals are frequent at both substrate/polymer and polymer/air interfaces. In conclusion, molecular simulations can shed light on the microscopic mechanisms of polymer crystallization under nano-confinement.


Simultaneous measurements of K+ and calcein release from liposomes and the determination of pore size formed in a membrane.
The changes induced by biologically active substances in the permeability to K+ and calcein of liposomes composed of egg phosphatidylcholine and cholesterol were measured simultaneously in order to rapidly screen the sizes of pores formed in a membrane, using different sized markers. The substances examined in the present study were classified into three types based on differences in the rates at which K+ and calcein were released. The first type released only K+, and included gramicidin A. The second type predominantly released K+, preceding the release of calcein, and included amphotericin B and nystatin. The third type, including antimicrobial peptides, such as gramicidin S, alamethicin, and melittin, and several membrane-active drugs, like celecoxib (non-steroidal anti-inflammatory drug), 1-dodecylazacycloheptan-2-one (named azone; skin permeation enhancer), and chlorpromazine (tranquilizer), caused the release of K+ and calcein simultaneously. Thus, the sizes of pores formed in a liposomal membrane increased in the following order: types one, two, and three. We determined the size more precisely by conducting an osmotic protection experiment, measuring the release of calcein in the presence of osmotic protectants of different sizes. The radii of pores formed by the second type, amphotericin B and nystatin, were 0.36 - 0.46 nm, while the radii of pores formed by the third type were much larger, 0.63 - 0.67 nm or more. The permeability changes induced by substances of the third type are discussed in connection with a transient pore formed in a lipid packing mismatch taking place during the phase transition of dipalmitoylphosphatidylcholine liposomes.


Increase in apparent diffusion coefficient in normal appearing white matter following human traumatic brain injury correlates with injury severity.
Following diffuse traumatic brain injury, there may be persistent functional or psychological deficits despite the presence of normal conventional MR images. Previous experimental animal and human studies have shown diffusion abnormalities following focal brain injury. Our aim was to quantify changes in apparent diffusion coefficient (ADC) and absolute relaxation times of normal appearing white matter (NAWM) in humans following traumatic brain injury. Twenty-three patients admitted with a diagnosis of head injury (nine mild, eight moderate, and six severe) were scanned an average of 7.6 days after injury using a quantitative echo planar imaging acquisition to obtain co-registered T1, T2, and ADC parametric maps. Mean NAWM values were compared with a control group (n = 13). The patient group showed a small but significant increase in ADC in NAWM, with no significant change in T1 or T2 relaxation times. There was a correlation between injury severity and increasing ADC (p = 0.03) but no correlation with either T1 or T2, suggesting that ADC is a sensitive and independent marker of diffuse white matter tissue damage following traumatic insult. None of the patients had a reduced ADC, making ischaemia unlikely in this cohort. Pathophysiological mechanisms that may explain diffusely raised ADC include vasogenic edema, chronic ischemic phenomena, or changes in tissue cytoarchitecture or neurofilament alignment.


Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force.
Dementia is a large and growing problem but is often not diagnosed in its earlier stages. Screening and earlier treatment could reduce the burden of suffering of this syndrome. To review the evidence of benefits and harms of screening for and earlier treatment of dementia. MEDLINE, PsycINFO, EMBASE, the Cochrane Library, experts, and bibliographies of reviews. The authors developed eight key questions representing a logical chain between screening and improved health outcomes, along with eligibility criteria for admissible evidence for each question. Admissible evidence was obtained by searching the data sources. Two reviewers abstracted relevant information using standardized abstraction forms and graded article quality according to U.S. Preventive Services Task Force criteria. No randomized, controlled trial of screening for dementia has been completed. Brief screening tools can detect some persons with early dementia (positive predictive value < or =50%). Six to 12 months of treatment with cholinesterase inhibitors modestly slows the decline of cognitive and global clinical change scores in some patients with mild to moderate Alzheimer disease. Function is minimally affected, and fewer than 20% of patients stop taking cholinesterase inhibitors because of side effects. Only limited evidence indicates that any other pharmacologic or nonpharmacologic intervention slows decline in persons with early dementia. Although intensive multicomponent caregiver interventions may delay nursing home placement of patients who have caregivers, the relevance of this finding for persons who do not yet have caregivers is uncertain. Other potential benefits and harms of screening have not been studied. Screening tests can detect undiagnosed dementia. In persons with mild to moderate clinically detected Alzheimer disease, cholinesterase inhibitors are somewhat effective in slowing cognitive decline. The effect of cholinesterase inhibitors or other treatments on persons with dementia detected by screening is uncertain.


A case with a ring chromosome 13 in a cohort of 203 children with non-syndromic autism and review of the cytogenetic literature.
Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the FMR1 gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The MCF2L and UPF3A genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).


Oestradiol-induced changes in the composition of phospholipid classes of quail oviduct: specific replacement of arachidonic acid by docosahexaenoic acid in alkenylacyl-glycerophosphoethanolamine.
The phospholipid composition and the molecular species of the major subclasses of ethanolamine and choline glycerophospholipids were determined during the natural or oestradiol-induced development of the quail oviduct. The phospholipid concentration increased significantly during oviduct development, and the proportion of ethanolamine glycerophospholipids (EPL) remained constant while that of choline glycerophospholipids increased. The immature oviduct contained the majority of its endogenous arachidonic acid mass (71%) in EPL, mainly in alkenylacyl-glycerophosphoethanolamine (alkenylacyl-GPE) (49% of the total). Oestrogen treatment induced the depletion of 20:4,n-6 specifically from this pool, which indicates the biological importance of 20:4,n-6 molecular species in alkenylacyl-GPE as substrates for the oviduct phospholipases activated by oestradiol, and suggests that this EPL subclass is involved in the oestrogen-induced cell proliferation. Another striking result was the marked increase in 22:6,n-3 EPL molecular species following the oestradiol treatment and more particularly the strict substitution of 20:4,n-6 by 22:6,n-3 in alkenylacyl-GPE. We speculate that alkenylacyl-GPE molecular species containing 22:6,n-3 may participate in the arrest of oestrogen-induced proliferation.


LY6E impairs coronavirus fusion and confers immune control of viral disease.
Zoonotic coronaviruses (CoVs) are significant threats to global health, as exemplified by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . Host immune responses to CoV are complex and regulated in part through antiviral interferons. However, the interferon-stimulated gene products that inhibit CoV are not well characterized 2 . Here, we show that interferon-inducible lymphocyte antigen 6 complex, locus E (LY6E) potently restricts cellular infection by multiple CoVs, including SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Importantly, mice lacking Ly6e in hematopoietic cells were highly susceptible to murine CoV infection. Exacerbated viral pathogenesis in Ly6e knockout mice was accompanied by loss of hepatic and splenic immune cells and reduction in global antiviral gene pathways. Accordingly, we found that Ly6e directly protects primary B cells and dendritic cells from murine CoV infection. Our results demonstrate that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis. These findings advance our understanding of immune-mediated control of CoV in vitro and in vivo , knowledge that could help inform strategies to combat infection by emerging CoV.


3,5-T2-A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action.
Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources.


High yield of culture-based diagnosis in a TB-endemic setting.
In most of the world, microbiologic diagnosis of tuberculosis (TB) is limited to microscopy. Recent guidelines recommend culture-based diagnosis where feasible. In order to evaluate the relative and absolute incremental diagnostic yield of culture-based diagnosis in a high-incidence community in Cape Town, South Africa, subjects evaluated for suspected TB had their samples processed for microscopy and culture over a 21 month period. For 2537 suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one positive smear and 29.9% (760) had at least one positive culture. One culture yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0% (absolute yield). Based on the latter value, the number of cultures needed to diagnose (NND) one extra case of TB was 8, compared to 19 if second specimens were submitted for microscopy. In a high-burden setting, the introduction of culture can markedly increase TB diagnosis over microscopy. The concept of number needed to diagnose can help in comparing incremental yield of diagnosis methods. Although new promising diagnostic molecular methods are being implemented, TB culture is still the gold standard.


Age-related inequalities in colon cancer treatment persist over time: a population-based analysis.
Older people experience poorer outcomes from colon cancer. We examined if treatment for colon cancer was related to age and if inequalities changed over time. Data from the UK population-based Northern and Yorkshire Cancer Registry on 31 910 incident colon cancers (ICD10 C18) diagnosed between 1999-2010 were obtained. Likelihood of receipt of: (1) cancer-directed surgery, (2) chemotherapy in surgical patients, (3) chemotherapy in non-surgical patients by age, adjusting for sex, area deprivation, cancer stage, comorbidity and period of diagnosis, was examined. Age-related inequalities in treatment exist after adjustment for confounding factors. Patients aged 60- 69, 70-79 and 80+ years were significantly less likely to receive surgery than those aged <60 years (multivariable ORs (95% CI) 0.84(0.74 to 0.95), 0.54(0.48 to 0.61) and 0.19(0.17 to 0.21), respectively). Age-related differences in receipt of surgery and adjuvant chemotherapy (but not chemotherapy in non-surgical patients) narrowed over time for the 'younger old' (aged <80 years) but did not diminish for the oldest patients. Age inequality in treatment of colon cancer remains after adjustment for confounders, suggesting age remains a major factor in treatment decisions. Research is needed to better understand the cancer treatment decision-making process, and how to influence this, for older patients.


Investigating the predictive roles of working memory and IQ in academic attainment.
There is growing evidence for the relationship between working memory and academic attainment. The aim of the current study was to investigate whether working memory is simply a proxy for IQ or whether there is a unique contribution to learning outcomes. The findings indicate that children's working memory skills at 5 years of age were the best predictor of literacy and numeracy 6 years later. IQ, in contrast, accounted for a smaller portion of unique variance to these learning outcomes. The results demonstrate that working memory is not a proxy for IQ but rather represents a dissociable cognitive skill with unique links to academic attainment. Critically, we find that working memory at the start of formal education is a more powerful predictor of subsequent academic success than IQ. This result has important implications for education, particularly with respect to intervention.


Biological defence mechanism in the pathogenesis of prolonged cerebral vasospasm in the patients with ruptured intracranial aneurysms.
We examined the relationship between the biological protective mechanisms of scavengers and free radicals that are elicited by subarachnoid hemorrhage (SAH) in the pathogenesis of prolonged vasospasm following ruptured intracranial aneurysm. The study included 25 patients treated by early surgery (within 72 hours after SAH). Lipid peroxides concentrations and the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px) in the cerebrospinal fluid (CSF) were measured. The concentration of lipid peroxides increased significantly more (p less than 0.05) during the first 4 days after SAH in patients with symptomatic vasospasm than in those without. Patients with symptomatic vasospasm had a marked decrease in SOD activity on Days 3 and 4 followed by a gradual decrease, whereas the patients without spasm showed little change (difference between the groups, p less than 0.05). There was a significant difference in catalase activity reversal to SOD activity, but no difference in GSH-px activity. Thus, correlation was close between the increased lipid peroxides concentration and the decrease in SOD activity in CSF (p less than 0.05), suggesting an important mechanism in the pathogenesis of vasospasm.


SU-D-218-01: Support Vector Machine Tissue Classification of Multiparametric MRI Tumor Data.
To test the accuracy of Support Vector Machines in the classification of Glioblastoma Multiforme tumor voxels usingmultiparametric MRI data. Various MRI scans were collected from patients with recurrent GBM. Each scan session collected post-contrastT1(+C T1), T2, diffusion, perfusion, and multi-echo hypoxia images. Thediffusion-weighted images were converted to Apparent Diffusion Coefficient (ADC) maps. The perfusion images were corrected for leakage and represented as corrected rCBV maps. All of these scans were co-registered to each other, giving an input matrix to our support vector machine consisting of roughly 13,000 voxels, each with 5 feature values (+C T1, T2, ADC, rCBVcorrected, delta T2*). The SVM was then trained usingradiologist confirmed labels for 'cyst', 'tumor', and 'normal tissue'. These labels were obtained using longitudinal data as well as clinical scans, and tested on new data to determine the accuracy of classifying tumor and cyst voxels. The tumor model resulted in a specificity of 0.9841 and a sensitivity of 0.7498. The cyst model resulted in a specificity of 0.9825 anda sensitivity of 0.9414. Both models showed improvement with increasing features. These results show that the SVM is capable of classifying tumor and cyst voxels in a single case study. Aside from optimizing the current tumor model, future work will focus on the potential for the SVM to help in early detection of recurrence. In order to achieve this,we will need to test SVMs across patients. If we truly aim for early detection, then we need to prove that the algorithm can be trained on a pool of subjects with recurrent disease, and then test that model on a new patient before recurrence is obvious.


Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials.
To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. Systematic review and network meta-analysis of randomised trials. Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (-1.88 mg/dL, moderate certainty) and moderate macronutrient (-0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. PROSPERO CRD42015027929.


Generation and functional characterization of mice with a conditional BMP7 allele.
Bone Morphogenetic Proteins (BMPs) play multiple and important roles in embryonic development as well as in homeostasis and tissue repair in the adult. Bmp7 has been implicated in developmental disorders and in a variety of diseases, but functional studies to elucidate its role so far have been hampered, since mice deficient in BMP7 die around or just after birth. To facilitate such studies, we generated mice in which the Bmp7 gene has been rendered conditional-null by flanking its first coding exon with loxP sites. To this end, we adapted the two-loxP site strategy to Bacterial Homologous Recombination to create a Bacterial Artificial Chromosome-based vector for direct targeting in mouse embryonic stem cells. Functional analysis showed that in vivo, the conditional-null Bmp7(flx/flx) mice are phenotypically wild type, whereas post Cre-mediated recombination, the resulting Bmp7(delta/delta) mice are phenotypically null. Thus, this study validates the usefulness of the Bmp7(flx/flx) mouse which in turn should empower in vivo studies aimed at elucidating the roles of Bmp7 in postnatal development, homeostasis and disease.


Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution.
In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and nonrelapse mortality after reduced intensity allogeneic transplantation. However, it also delays immune reconstitution, leading to frequent infections and potential loss of graft-versus-tumor responses. Here, we tested the feasibility of alemtuzumab dose deescalation in the context of fludarabine-melphalan conditioning and human leukocyte antigen (HLA)-identical sibling transplantation. Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were fitted to a linear, 2-compartment model in which dose reduction led to incomplete saturation of CD52 binding sites and greater antibody clearance. Increased elimination was particularly evident in the 20-mg group in patients who had CD52-expressing tumors at time of transplantation. The 20-mg dose was also associated with greater risk of severe GVHD (acute grade III-IV or chronic extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In contrast, dose reduction to 30 mg on day -1 was associated with equivalent clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced intensity conditioning and HLA-identical sibling transplantation. This trial was registered at http://www.ncrn.org.uk as UKCRN study 1415.


Novel cycloartane triterpenoid from Cimicifuga foetida (Sheng ma) induces mitochondrial apoptosis via inhibiting Raf/MEK/ERK pathway and Akt phosphorylation in human breast carcinoma MCF-7 cells.
Cycloartane triterpenoids exhibited anticancer effects. This study aims to identify any potential novel anticancer cycloartane triterpenoids from Cimicifuga foetida L. rhizome (Sheng ma) and the mode of actions. Cycloartane triterpenoids were isolated from the C. foetida rhizome by a series of column chromatography and identified by IR, MS and NMR. Their anticancer effects on several human cancer cell lines, MCF-7, HepG2, HepG2/ADM, HeLa, and PC3, and normal human mammary epithelial cells MCF10A were investigated by colony formation and MTT assays. Morphological analysis of apoptosis induction was performed by acridine orange/ethidium bromide dual-staining and Hoechst 33258 nuclear staining. The cell-cycle profile and annexin V staining were evaluated by flow cytometry. Apoptosis were investigated by measuring changes in mitochondrial membrane potential and analyzing expression of cell cycle- and apoptosis-related proteins in MCF-7 cells by Western blotting. A novel cycloartane triterpenoid, 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-d-(2-acetyl)xylopyranoside (ADHC-AXpn), together with the known 7,8-didehydrocimigenol-3-O-β-d-xylopyranoside (DHC-Xpn) were isolated. MCF-7 growth was significantly inhibited by ADHC-AXpn in a dose- and time-dependent manner (IC50: 27.81 µM at 48 h; P = 0.004 vs. control at 25 μM for 48 h treatment), and ADHC-AXpn was selectively cytotoxic for cancerous cells (MCF-7, HepG2/ADM, HepG2 and HELA cells) based on its higher IC50 values for normal cells MCF10A (IC50: 78.63 µM at 48 h) than for tumor cells. In MCF-7 cells, ADHC-AXpn induced G2/M cell cycle arrest by mediating cyclin-B1, and CDK1 and its phosphorylation; and induced apoptosis through the mitochondrial-mediated apoptotic pathway, with inhibition of Akt activation. As ADHC-AXpn suppressed phosphorylation of ERK1/2, Raf and Akt proteins in MCF-7 cells, its apoptotic effect might be associated with Raf/MEK/ERK signaling and Akt activation. ADHC-AXpn significantly suppressed the growth of MCF-7 cells, induced mitochondrial apoptosis and cell-cycle arrest, and inhibited Raf/MEK/ERK signaling pathway and Akt phosphorylation.


Parental hopes for therapy outcomes: children with sensory modulation disorders.
Understanding parents' hopes for therapy outcomes is essential to family-centered care. This qualitative study explored parents' points of view regarding their hopes for the outcomes of occupational therapy using a sensory integration treatment approach. Data were collected as part of a larger research project on the effectiveness of rehabilitating children who have sensory modulation disorders. Five interviews were randomly selected from 17 parent interviews conducted in the larger study. Data were analyzed using grounded theory methods. Three themes pertinent to the occupations of children and two themes related to the occupations of parenting and sustaining family life emerged. Child-focused outcomes include social participation, self-regulation, and perceived competence. Parent-focused outcomes include learning strategies to support children and obtaining personal validation. Interventions are proposed that relate to children's participation in contexts in which they live, learn, and play, as well as the support of parents in the occupations of parenting.


N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex.
Although many eukaryotic proteins are amino (N)-terminally acetylated, structural mechanisms by which N-terminal acetylation mediates protein interactions are largely unknown. Here, we found that N-terminal acetylation of the E2 enzyme, Ubc12, dictates distinctive E3-dependent ligation of the ubiquitin-like protein Nedd8 to Cul1. Structural, biochemical, biophysical, and genetic analyses revealed how complete burial of Ubc12's N-acetyl-methionine in a hydrophobic pocket in the E3, Dcn1, promotes cullin neddylation. The results suggest that the N-terminal acetyl both directs Ubc12's interactions with Dcn1 and prevents repulsion of a charged N terminus. Our data provide a link between acetylation and ubiquitin-like protein conjugation and define a mechanism for N-terminal acetylation-dependent recognition.


Transfer of Patients with Spontaneous Intracranial Hemorrhage who Need External Ventricular Drain: Does Admission Location Matter?
Patients with spontaneous intracranial hemorrhage (sICH) are associated with high mortality and require early neurosurgical interventions. At our academic referral center, the neurocritical care unit (NCCU) receives patients directly from referring facilities. However, when no NCCU bed is immediately available, patients are initially admitted to the critical care resuscitation unit (CCRU). We hypothesized that the CCRU expedites transfer of sICH patients and facilitates timely external ventricular drain (EVD) placement comparable to the NCCU. This is a pre-post study of adult patients transferred with sICH and EVD placement. Patients admitted between January 2011-July 2013 (2011 Control) were compared with patients admitted either to the CCRU or the NCCU (2013 Control) between August 2013-September 2015. The primary outcome was time interval from arrival at any intensive care units (ICU) to time of EVD placement (ARR-EVD). Secondary outcomes included time interval from emergency department transfer request to arrival, and in-hospital mortality. We assessed clinical association by multivariable logistic regressions. We analyzed 259 sICH patients who received EVDs: 123 (48%) CCRU; 81 (31%) 2011 Control; and 55 (21%) in the 2013 Control. The groups had similar characteristics, age, disease severity, and mortality. Median ARR-EVD time was 170 minutes [106-311] for CCRU patients; 241 minutes [152-490] (p < 0.01) for 2011 Control; and 210 minutes [139-574], p = 0.28) for 2013 Control. Median transfer request-arrival time for CCRU patients was significantly less than both control groups. Multivariable logistic regression showed each minute delay in ARR-EVD was associated with 0.03% increased likelihood of death (odds ratio 1.0003, 95% confidence interval, 1.0001-1.006, p = 0.043). Patients admitted to the CCRU had shorter transfer times when compared to patients admitted directly to other ICUs. Compared to the specialty NCCU, the CCRU had similar time interval from arrival to EVD placement. A resuscitation unit like the CCRU can complement the specialty unit NCCU in caring for patients with sICH who require EVDs.


[Survey of risk factors and renal disease in first-degree relatives of dialysis patients].
It has been established that first-degree relatives of patients with chronic kidney disease (CKD) have a higher CKD risk than the overall population. This paper deals with the relative frequency of CKD markers and cardiovascular (CV) risk factors within first-degree relatives of ESRD patients in Argentina. 810 family members volunteered to participate; of them 668 over 18 ys. old. Trained nurses interviewed them and completed a questionnaire dealing with family history of renal and cardiovascular disease. Blood pressure, urine and blood analysis and anthropometric data were collected. Selected parameters were: smoking habit, presence of high blood pressure, diabetes, hypercholesterolemia, high plasma creatinine and creatinine clearance estimated by MDRD formula, proteinuria and microalbuminuria. In pediatric population, weight and blood pressure parameters were evaluated as percentiles. CKD were classified in stage (National Kidney Foundation). The relative frequencies were: CKD: 29.6%; proteinuria: 13.9%; microalbuminuria: 8.7%. The prevalence values found for main CV risks factors, adjusted by sex and age, were: high blood pressure= 41.8%; overweight/obesity by BMI= 62.1%, hypercholesterolemia= 42.9% and hyperglycemia= 5.2%. Smoking habit was present in 34.8%. Prevalence of overweight/obesity, hypertension and hypercholesterolemia in first-degree relatives of ESRD patients is higher than previously communicated in studies of national reference populations. Prevalence of CKD is high, estimated as three-fold higher than for a general population as reported in poblational studies. These results support the fact that first-degree relatives of ESRD patients, as has been established elsewhere, constitute a population at high risk for developing ESRD.


Nuclei of chicken neurons in tissues and three-dimensional cell cultures are organized into distinct radial zones.
We used chicken retinospheroids (RS) to study the nuclear architecture of vertebrate cells in a three-dimensional (3D) cell culture system. The results showed that the different neuronal cell types of RS displayed an extreme form of radial nuclear organization. Chromatin was arranged into distinct radial zones which became already visible after DAPI staining. The distinct zones were enriched in different chromatin modifications and in different types of chromosomes. Active isoforms of RNA polymerase II were depleted in the outermost zone. Also chromocenters and nucleoli were radially aligned in the nuclear interior. The splicing factor SC35 was enriched at the central zone and did not show the typical speckled pattern of distribution. Evaluation of neuronal and non-neuronal chicken tissues showed that the highly ordered form of radial nuclear organization was also present in neuronal chicken tissues. Furthermore, the data revealed that the neuron-specific nuclear organization was remodeled when cells spread on a flat substrate. Monolayer cultures of a chicken cell line did not show this extreme form of radial organization. Rather, such monolayer cultures displayed features of nuclear organization which have been described before for many different types of monolayer cells. The finding that an extreme form radial nuclear organization, which has not been described before, is present in RS and tissues, but not in cells spread on a flat substrate, suggests that it would be important to complement studies on nuclear architecture performed with monolayer cells by studies on 3D cell culture systems and tissues.


Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells.
Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H(2)O(2)) reduced the expression of catalase. H(2)O(2) increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxO1 transcription factor. Further analysis revealed that H(2)O(2) promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxO1 phosphorylation and preventing the downregulating effect of H(2)O(2) on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H(2)O(2) on expression of catalase. Constitutively active FoxO1 increased the expression of catalase. However, dominant negative FoxO1 inhibited catalase protein level. Catalase transcription was reduced by H(2)O(2) treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxO1 increased catalase transcription, respectively. These results demonstrate that ROS downregulate the expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1 as a target.


Effect of the Obesity Paradox on Mortality in Patients with Acute Coronary Syndrome: A Comprehensive Meta-analysis of the Literature
The protective effect of obesity in patients with acute coronary syndrome undergoing percutaneous coronary intervention or bypass surgery has been described as the obesity paradox in the literature. In this comprehensive meta-analysis, we aimed to investigate the pooled effect of the obesity paradox on mortality in acute coronary syndrome patients. Systemic meta-analysis and metaregression. We searched PubMed, Google Scholar, and the Cochrane Library for eligible studies that compared the mortality rates between body mass index cut-off points in acute coronary syndrome patients. This meta-analysis comprised 54 studies with 534,903 patients. Random- and fixed-effect models were used to calculate pooled effects sizes in the presence of moderately high and low heterogeneity between studies, respectively. A metaregression analysis was used to detect possible causes of heterogeneity. A dose-response meta-analysis was also conducted to detect the association between mortality risk and body mass index. Overweight patients had lower mortality risk for 30-day (RR =0.69; 0.62-0.76, p < 0.01) and long-term (RR =0.73; 0.70-0.77, p < 0.01) mortality than normal-weight patients. The 30-day mortality risk was higher in low-weight patients than in normal-weight patients (RR =1.74; 1.39-2.18, p < 0.01). Meta-regression could not explain the possible causes of between-study heterogeneity. Patients with body mass index <21.5 kg/m2 and >40 kg/m2 had a higher risk of mortality, which was lowest at approximately 30 kg/m2. Low-weight and overweight acute coronary syndrome patients had higher mortality risk than normal-weight patients. A U-shaped nonlinear association was detected between body mass index and mortality risk.


Juvenile psoriatic arthritis and HLA antigens.
The clinical, laboratory, and radiological features, including histocompatibility typing, of 28 patients with juvenile psoriatic arthritis are reported. The most common presentation was that of psoriasis preceding or occurring simultaneously with arthritis. The most common course of juvenile psoriatic arthritis was to start as an oligoarthritis and progress, usually to polyarthritis. No patients with juvenile psoriatic arthritis had uveitis. Overall, most patients had a good outcome (93% in functional class I and II), though 8/28 (29%) did require disease modifying drugs over a mean period of 8.8 years of follow up. The clinical features of these patients were very similar to those of a group of 158 adult patients with psoriatic arthritis with the same disease duration followed up in the clinic. Although there was an increased prevalence of B17 in both juvenile and adult psoriatic arthritis, juvenile psoriatic arthritis showed increased prevalence of A2, whereas adult psoriatic arthritis showed increased prevalence of B27, Bw39, and Cw6. This HLA association differed from that reported in other forms of juvenile arthritis.


Suicide, fatal injuries, and other causes of premature mortality in patients with traumatic brain injury: a 41-year Swedish population study.
: Longer-term mortality in individuals who have survived a traumatic brain injury (TBI) is not known. To examine the relationship between TBI and premature mortality, particularly by external causes, and determine the role of psychiatric comorbidity. We studied all persons born in 1954 or later in Sweden who received inpatient and outpatient International Classification of Diseases-based diagnoses of TBI from 1969 to 2009 (n = 218,300). We compared mortality rates 6 months or more after TBI to general population controls matched on age and sex (n = 2,163,190) and to unaffected siblings of patients with TBI (n = 150,513). Furthermore, we specifically examined external causes of death (suicide, injury, or assault). We conducted sensitivity analyses to investigate whether mortality rates differed by sex, age at death, severity (including concussion), and different follow-up times after diagnosis. Adjusted odds ratios (AORs) of premature death by external causes in patients with TBI compared with general population controls. Among those who survived 6 months after TBI, we found a 3-fold increased odds of mortality (AOR, 3.2; 95% CI, 3.0-3.4) compared with general population controls and an adjusted increased odds of mortality of 2.6 (95% CI, 2.3-2.8) compared with unaffected siblings. Risks of mortality from external causes were elevated, including for suicide (AOR, 3.3; 95% CI, 2.9-3.7), injuries (AOR, 4.3; 95% CI, 3.8-4.8), and assault (AOR, 3.9; 95% CI, 2.7-5.7). Among those with TBI, absolute rates of death were high in those with any psychiatric or substance abuse comorbidity (3.8% died prematurely) and those with solely substance abuse (6.2%) compared with those without comorbidity (0.5%). Traumatic brain injury is associated with substantially elevated risks of premature mortality, particularly for suicide, injuries, and assaults, even after adjustment for sociodemographic and familial factors. Current clinical guidelines may need revision to reduce mortality risks beyond the first few months after injury and address high rates of psychiatric comorbidity and substance abuse.


Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.
The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. http://www.clinicaltrials.gov. Unique identifier: NCT00979199.


Reproduction and Damage Potential of Five Geographical Ditylenchus africanus Populations on Peanut.
Ditylenchus africanus affects peanut quality, which leads to downgrading of consignments and economic losses for producers. This nematode is difficult to control and host-plant resistance may be the most effective way to control it. Recently, the peanut breeding line PC254K1 has been identified as resistant to a D. africanus population from Vaalharts and will be included into the peanut breeding program. The objectives of our study were to compare the reproduction potential of D. africanus geographic populations from five different areas in the peanut production area of South Africa and to assess whether PC254K1 is resistant to all five D. africanus populations. Reproduction of the D. africanus populations was evaluated on peanut callus in growth cabinets at 21°C, 28°C, and 35°C. The peanut cv. Sellie was included in the study as the D. africanus-susceptible reference genotype in the greenhouse and microplots. Reproduction potential of all five of the D. africanus populations was similar. Resistance of PC254K1 was confirmed to all five D. africanus populations. The resistance trait of a D. africanus-resistant cultivar developed from PC254K1 should, therefore, be sustainable over the five localities tested during this study.


Attention-Guided Progressive Neural Texture Fusion for High Dynamic Range Image Restoration.
High Dynamic Range (HDR) imaging via multi-exposure fusion is an important task for most modern imaging platforms. In spite of recent developments in both hardware and algorithm innovations, challenges remain over content association ambiguities caused by saturation, motion, and various artifacts introduced during multi-exposure fusion such as ghosting, noise, and blur. In this work, we propose an Attention-guided Progressive Neural Texture Fusion (APNT-Fusion) HDR restoration model which aims to address these issues within one framework. An efficient two-stream structure is proposed which separately focuses on texture feature transfer over saturated regions and multi-exposure tonal and texture feature fusion. A neural feature transfer mechanism is proposed which establishes spatial correspondence between different exposures based on multi-scale VGG features in the masked saturated HDR domain for discriminative contextual clues over the ambiguous image areas. A progressive texture blending module is designed to blend the encoded two-stream features in a multi-scale and progressive manner. In addition, we introduce several novel attention mechanisms, i.e., the motion attention module detects and suppresses the content discrepancies among the reference images; the saturation attention module facilitates differentiating the misalignment caused by saturation from those caused by motion; and the scale attention module ensures texture blending consistency between different coder/decoder scales. We carry out comprehensive qualitative and quantitative evaluations and ablation studies, which validate that these novel modules work coherently under the same framework and outperform state-of-the-art methods.


Method for selection of femoral component in total knee arthroplasty (tka).
A method is proposed enabling a surgeon to preoperatively determine the preeminent type and size of prosthesis, from those available, to be used in a particular patient undergoing knee replacement surgery. Parameters of healthy knee geometry were estimated by employing an unsupervised neural network. These estimated parameters were then applied in a χ(2) goodness of fit (GoF) test to determine which femoral prosthesis type and size delivers the most appropriate fit. This approach was used to determine the most suitable match of three implants for 34 different cases. Implant C performed the best and was the optimal fit in 59% of the cases, Implant A was the best fit in 38% of the cases and Implant B the best fit in 3% of the cases. This method shows promise in aiding a surgeon to select the optimal prosthesis type and size from an array of different conventional total knee replacements.


Radar mapping, archeology, and ancient maya land use.
A severe incongruity has long existed between the well-known complexity of ancient Maya civilization and the relatively feeble economic base that could be reconstructed for it. Recent fieldwork has ihdicated that much more intensive cultivation patterns were used than was previously thought. Data from the use of synthetic aperture radar in aerial surveys of the southern Maya lowlands suggest that large areas were drained by ancient canals that may have been used for intensive cultivation. Ground checks in several limited areas have confirmed the existence of canals, and excavations and ground surveys have provided valuable comparative information. Taken together, the new data suggest that Late Class period Maya civilization was firmly grounded in large-scale and intensive cultivation of swampy zones.


The SafeBoosC phase II clinical trial: an analysis of the interventions related with the oximeter readings.
The SafeBoosC phase II randomised clinical trial recently demonstrated the benefits of a combination of cerebral regional tissue oxygen saturation (rStO2) by near-infrared spectroscopy (NIRS) and a treatment guideline to reduce the oxygen imbalance in extremely preterm infants. To analyse rStO2-alarm-related clinical decisions and their heterogeneity in the NIRS experimental group (NIRS monitoring visible) and their impact on rStO2 and SpO2. Continuous data from NIRS devices and the alarms (area under the curve of the rStO2 out of range had accumulated 0.2%h during 10 min), clinical data at discrete time points and interventions prompted by the alarms were recorded. Sixty-seven infants had data that fulfilled the requirements for this analysis. 1107 alarm episodes were analysed. The alarm triggered a treatment guideline intervention in 25% of the cases; the type of intervention chosen varied among clinical sites. More than 55% of alarms were not followed by an intervention ('No action'); additionally, in 5% of alarms the rStO2 value apparently was considered non-reliable and the sensor was repositioned. The percentage of unresolved alarms at 30 min after 'No action' almost doubled the treatment guideline intervention (p<0.001). Changes in peripheral oxygen saturation (SpO2), were observed only after treatment guideline interventions. This study shows that 25% of rStO2 alarms were followed by a clinical intervention determined by the treatment guideline. However, the rStO2 and SpO2 returned to normal ranges after the intervention, supporting the notion that decisions taken by the clinicians were appropriate. ClinicalTrial.gov NCT01590316.


Fluoroscopically guided diagnostic and therapeutic injections into foot articulations: report of short-term patient responses and comparison of outcomes between various injection sites.
A few studies have reported on short-term outcomes of patients receiving imaging-guided injections into the foot articulations, but none have compared patient responses depending on the anatomic site injected. This study includes a large sample size facilitating the investigation of postinjection pain reduction overall and by specific articulation. Three hundred forty-eight patients with imaging-guided diagnostic or therapeutic injections into the foot articulations, with complete preinjection and 20- to 30-minute postinjection numeric rating scale pain data were included. The proportions of patients reporting clinically relevant pain reduction (≥ 50%) were calculated overall and for specific subgroups. The risk ratio comparing patients with osteoarthritis to those without osteoarthritis was calculated. Analysis of variance was used to compare outcomes between subgroups of patients based on injection site. The unpaired Student t test was used to compare responses of men versus women, those with and without a diagnosis of osteoarthritis, and more experienced versus less experienced radiologists. Sixty-four percent of patients (224/348) reported clinically relevant pain reduction. The average decrease overall was 56% (SD, 36). Injections into the Lisfranc articulation were significantly more effective (61% pain reduction, p = 0.007) compared with other sites, with 74% of patients obtaining clinically relevant pain relief. Patients with osteoarthritis reported more relief (62%) compared with those without (50%, p = 0.002). No difference in outcomes comparing musculoskeletal radiologists with residents or fellows in training was found. Nearly two thirds of patients receiving imaging-guided injections into the foot articulations reported clinically relevant pain reduction. Lisfranc joint injections and patients with a diagnosis of osteoarthritis responded better.


Lattice resonances in antenna arrays for liquid sensing in the terahertz regime.
Terahertz antenna arrays supporting narrow lattice resonances are proposed as an alternative sensor-on-chip approach to liquid sensing. An array of metallic rectangular antennas fabricated on a polyethylene naphthalate (PEN) substrate is used to demonstrate the sensing of a number of fluids. Good agreement is shown between experiment and simulation with Q-factors of around 20 and a figure-of-merit (FOM) of 3.80 being achieved. Liquid sensing with antenna arrays is simple both in terms of fabrication and setup. The working frequency can be tuned with a suitable choice of substrates and array parameters. The nature of the lattice resonance means that the whole sample is used to provide the conditions required for resonance occurrence, eliminating the need to preferentially locate the sample in small areas of high field concentration. The antenna arrays could also potentially be coupled with a microfluidic system for in situ sensing or used in a reflection setup.


Lithiation-induced shuffling of atomic stacks.
In rechargeable lithium-ion batteries, understanding the atomic-scale mechanism of Li-induced structural evolution occurring at the host electrode materials provides essential knowledge for design of new high performance electrodes. Here, we report a new crystalline-crystalline phase transition mechanism in single-crystal Zn-Sb intermetallic nanowires upon lithiation. Using in situ transmission electron microscopy, we observed that stacks of atomic planes in an intermediate hexagonal (h-)LiZnSb phase are "shuffled" to accommodate the geometrical confinement stress arising from lamellar nanodomains intercalated by lithium ions. Such atomic rearrangement arises from the anisotropic lithium diffusion and is accompanied by appearance of partial dislocations. This transient structure mediates further phase transition from h-LiZnSb to cubic (c-)Li2ZnSb, which is associated with a nearly "zero-strain" coherent interface viewed along the [001]h/[111]c directions. This study provides new mechanistic insights into complex electrochemically driven crystalline-crystalline phase transitions in lithium-ion battery electrodes and represents a noble example of atomic-level structural and interfacial rearrangements.


Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects.
The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.


The incidence of exercise-associated hyponatraemia in the London marathon.
Exercise-associated hyponatraemia (EAH) is a potentially fatal cause of collapse in endurance exercise. It is understood to be a dilutional hyponatraemia caused by an increase of total body water relative to the amount of exchangeable sodium stores. Fourteen runners presented to one London hospital with symptomatic EAH several hours after finishing the 2003 London Marathon, and more recently, a young male runner died from the complications of severe EAH after crossing the finish line of the London Marathon. To determine the incidence of EAH in runners in the London Marathon. Volunteers were recruited at race registration where they were weighed, had blood tests and completed a demographic and experience questionnaire. Weights, blood tests and a fluid intake questionnaire were repeated after the finish. Blood was analysed on-site using hand-held i-STAT blood analysers. Of the 88 volunteers, 11 (12.5%) developed asymptomatic hyponatraemia (serum sodium 128-134 mmol/l). They consumed more fluid (p<0.001) and gained more weight (p<0.001) than did those without hyponatraemia. A significant proportion (12.5%) of healthy volunteers developed asymptomatic hyponatraemia running a marathon in cool conditions. On average, these runners consumed more fluid and gained more weight than did non-hyponatraemic runners, although fluid intake was not related to weight gain in this study. Four of the 11 hyponatraemic runners lost weight over the course of the marathon, strengthening the case for an additional factor, such as inappropriate antidiuretic hormone release during exercise, in the development of EAH.


Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions.
Tumor-associated macrophages (TAM) are causally associated with tumorigenesis as well as regulation of antitumor immune responses and have emerged as potential immunotherapeutic targets. Recent evidence suggests TAM phagocytose apoptotic tumor cells within the tumor microenvironment through efferocytosis in an immunologically silent manner, thus maintaining an immunosuppressed microenvironment. The signal transduction pathways coupling efferocytosis and immunosuppression are not well known. Neuropilin-2 (NRP2) is a member of the membrane-associated neuropilin family and has been reported in different immune cells but is poorly characterized. In this study, we show that NRP2 is expressed during macrophage differentiation, is induced by tumor cells, and regulates phagocytosis in macrophages. Furthermore, NRP2 in TAM promoted efferocytosis and facilitated tumor growth. Deletion of NRP2 from TAM impaired the clearance of apoptotic tumor cells and increased secondary necrosis within tumors. This resulted in a break in the immune tolerance and reinitiated antitumor immune responses, characterized by robust infiltration of CD8+ T and natural killer cells. This result suggests NRP2 may act as a molecular mediator that connects efferocytosis and immune suppression. Deletion of NRP2 in TAM downregulated several immunosuppressive and tumor-promoting genes and upregulated immunostimulatory genes in the myeloid compartment. Taken together, our study demonstrates that TAM-derived NRP2 plays a crucial role in tumor promotion through efferocytosis, opening the enticing option for the development of effective immunotherapy targeting TAM.Significance: Neuropilin-2 in macrophages promotes tumor growth by regulating efferocytosis of apoptotic tumor cells and orchestrating immune suppression.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/19/5600/F1.large.jpg Cancer Res; 78(19); 5600-17. ©2018 AACR.


Association of umbilical cord blood lead with neonatal behavior at varying levels of exposure.
In the light of the ongoing debate about lowering the cut-off for acceptable blood lead level to <5 microg/dL from the currently recommended level of <10 microg/dL, we considered whether prenatal exposure to varying levels of lead is associated with similar or disparate effects on neonatal behavior. Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an epidemiological approach and robust statistical techniques like multivariate linear regression, logistic regression, Poisson regression and structural equations modeling analyses we estimated the simultaneous indirect effects of umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS clusters. We observed that when analyzed in all study subjects, the CBL levels independently and strongly influenced autonomic stability and abnormal reflexes clusters. However, when the analysis was restricted to neonates with CBL <10 microg/dL, CBL levels strongly influenced the range of state, motor and autonomic stability clusters. Abnormal walking reflex was consistently associated with an increased CBL level irrespective of the cut-off for CBL, however, only at the lower cut-offs were the predominantly behavioral effects of CBL discernible. Our results further endorse the need to be cognizant of the detrimental effects of blood lead on neonates even at a low-dose prenatal exposure.


Patients' perceptions and experiences of the prevention of hospital-acquired thrombosis: a qualitative study.
To examine patients' understanding of hospital-associated thrombosis, and their experiences of thromboprophylaxis. Qualitative study using semi-structured interviews with 31 patients requiring venous thromboembolism (VTE) prophylaxis following a recent hospital admission. Interviews were audio-recorded, transcribed verbatim and analysed thematically using framework analysis. 4 hospitals in Birmingham and Oxford. All the participants received thromboprophylaxis following surgical procedures. Participants were aware of a risk of blood clots; however, they lacked a good understanding of VTE and its components. Experiences of VTE prophylaxis were characterised with good adherence to heparin injections and poor adherence to elastic compression stockings, largely due to perceived lack of clarity in guidance from health professionals. Participants had limited knowledge of the signs and symptoms of VTE and would value improved education on VTE. Findings suggest that patient education is often inadequate and impacts negatively on patients' involvement in VTE prevention. An enhanced patient education programme incorporating a consistent message on the appropriate use of elastic compression stockings and description of VTE symptoms is likely to optimise the effectiveness of the prevention of hospital-associated thrombosis. Physicians may use the results of this study to improve individual patient education.


Thrombotic microangiopathy in hematotoxic snakebites and its impact on the prognosis: an entity often overlooked.
Snakebite associated thrombotic microangiopathy (TMA) is a spectrum of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI). We carried out this study to find out the prevalence of TMA in hematotoxic snake envenomation and to analyze its impact on the clinical outcome of patients. Retrospective data were collected from the medical records, hospital and lab information system after institutional ethics committee approval. Hematotoxic snake bite patients were categorized into Group 1 (with TMA) and Group 2 (without TMA). Chi square test, Mann-Whitney 'U' test and Odd's ratio (OR) were used for statistical analysis. Out of 331 snakebite cases admitted, 202 (64.33%) were hematotoxic envenomation with a mean age of 42.26 ± 15.61. Majority were males with a male to female ratio of 2.01:1. Lower limb was the most common site of bite (59.9%). The prevalence of coagulopathy, TMA and AKI observed was 56.4, 18.8 and 37.6% respectively. AKI had a significant risk of undergoing hemodialysis when it was associated with TMA (r = 0.635, OR = 19.3182, P < 0.0001). Higher number of patients in Group 1 received more blood products (r = 0.406, OR = 8.525, P < 0.0001). Prolonged hospital stay (17.25 ± 12.23 vs. 8.86 ± 7.18 days, P < 0.0001) and higher complication rates were (33.33% vs. 11.4%, P < 0.0048) observed in patients with TMA. Snakebite associated TMA has a significant impact on the prognosis and understanding the pathophysiology of this entity will help to formulate guidelines.


Community-Based Prevalence Estimates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Gay, Bisexual, and Other Men Who Have Sex With Men in Montréal, Canada.
Reported cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are increasing among Canadian men. Estimates of community-based CT/NG prevalence are lacking among gay, bisexual, and other men who have sex with men (GBM). Respondent driven sampling was used to recruit GBM in Montréal, Canada between February 2017 and June 2018. Specimens provided from urogenital, rectal, and pharyngeal sites were analyzed using nucleic acid amplification test to detect CT/NG. Prevalence estimates of CT/NG, overall and by anatomical site were calculated. All estimates are respondent-driven sampling-adjusted. Among 1177 GBM, the prevalence of rectal, urogenital, pharyngeal and overall were respectively 2.4%, 0.4%, 0.4%, and 2.8% for CT infections, and 3.1%, 0.4%, 3.5%, and 5.6% for NG infections. If testing had been limited to the urogenital site, 80% and 94% of CT and NG infections, respectively, would have been missed. This community-based study among GBM shows that the CT prevalence was about half of that observed for NG. A large part of CT/NG infections involves only the extragenital sites, highlighting the need for systematic multisite screening regardless of symptoms. In the mist of the COVID-19 pandemic and the limited CT/NG screening capacity due to test kits shortage, it might be considered to prioritize rectal and pharyngeal CT/NG testing over urogenital testing in asymptomatic GBM.


Paternalism in practice: informing patients about expensive unsubsidised drugs.
Recent research conducted in Australia shows that many oncologists withhold information about expensive unfunded drugs in what the authors of the study suggest is unacceptable medical paternalism. Surprised by the Australian results, we ran a version of the study in New Zealand and received very different results. While the percentages of clinicians who would prescribe the drugs described in the scenarios were very similar (73-99% in New Zealand and 72-94% in Australia depending on the scenario) the percentage who would not discuss expensive unfunded drugs was substantially lower in New Zealand (6.4-11.1%) than it was in Australia (28-41%). This seems surprising given the substantial similarities between the two countries, and the extensive interaction between their medical professions. We use the contrast between the two studies to examine the generalisability of the Australian results, to identify influences on clinicians' decisions about what treatment information to give patients, and so the tendency towards medical paternalism and, more pragmatically, about how such decisions might be influenced.


An aqueous red emitting fluorescent fluoride sensing probe exhibiting a large Stokes shift and its application in cell imaging.
A novel red emitting fluorescent probe exhibiting a 143 nm Stokes shift for the detection of fluoride ions in an aqueous solution was developed. The probe displays a rapid response, high selectivity and good sensitivity towards F(-). Application of the probe for the selective detection of intracellular F(-) has been successfully demonstrated in living cells.


The importance of the epinephrine provocation test for the hidden type-1 congenital long QT syndrome.
Congenital long QT syndrome (LQTS) is a genetic channelopathy associated with a high incidence of sudden cardiac death in children and young adults. QT interval prolongation is typically the primary finding on the electrocardiography (ECG) recordings, but a normal QT interval may be seen in as many as 40% of patients with LQTS due to incomplete penetrance. A normal QT interval on ECG in patients with LQTS is known as hidden LQTS. An epinephrine provocation test can help in the diagnosis of hidden LQTS. This case report describes the use of an epinephrine provocation test to diagnose hidden LQTS in 3 patients who had normal QT interval and corrected QT interval on ECG and a family history of sudden cardiac death.


Detection of Bessel beams with digital axicons.
We propose a simple method for the detection of Bessel beams with arbitrary radial and azimuthal indices, and then demonstrate it in an all-digital setup with a spatial light modulator. We confirm that the fidelity of the detection method is very high, with modal cross-talk below 5%, even for high orbital angular momentum carrying fields with long propagation ranges. To illustrate the versatility of the approach we use it to observe the modal spectrum changes during the self-reconstruction process of Bessel beams after encountering an obstruction, as well as to characterize modal distortions of Bessel beams propagating through atmospheric turbulence.


Efficacy of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.
The use of intracytoplasmic sperm injection (ICSI) has dramatically increased in patients with non-male factor infertility during the last decades. However, whether ICSI provides a significant benefit over in vitro fertilization (IVF) in these patients is still controversial. In this study, we aimed to investigate the efficacy of ICSI on reproductive outcomes with non-male factor infertility and to provide updated evidence for clinical practice. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2023. Randomized controlled trials (RCTs) comparing the efficacy between ICSI and IVF in patients with non-male factor infertility were included. The main outcomes were the live birth rate (LBR), fertilization rate (FR), and total fertilization failure (TFF). The pooled estimates were calculated using the random-effects models as relative risk (RR) with 95% confidence intervals (CIs). This systematic review and meta-analysis was registered in PROSPERO (CRD42023427004). We included 18 RCTs with 3249 cycles and 30 994 oocytes. The results demonstrated that ICSI reduced the risk of TFF (RR = 0.26, 95% CI: 0.13-0.50, I2 = 58%) and increased FR per oocyte inseminated/injected (RR = 1.14, 95% CI: 1.08-1.20, I2 = 69%), but it did not improve LBR (RR = 1.11, 95% CI: 0.94-1.30, I2 = 0%) or other outcomes compared with IVF. However, the difference in fertilization failure reduction between ICSI and IVF may be explained by different randomization methods (randomization based on patients vs. sibling oocytes). When considering only studies with randomization based on patients, we found no evidence of the difference between the groups (RR = 0.72, 95% CI: 0.48-1.06, I2 = 0%). Furthermore, no differences were observed in subgroup analyses based on other factors, including female age, study period, and controlled ovarian stimulation protocols. Our findings suggest that ICSI leads to no difference in reproductive outcomes compared to IVF in patients with non-male factor infertility. Considering the cost and safety of ICSI, we have no evidence to support the routine use of ICSI in these populations. High-quality RCTs with large sample sizes will be needed to confirm our results and explore clinical and neonatal outcomes.


Mindfulness for adolescents: a promising approach to supporting emotion regulation and preventing risky behavior.
This article reviews the contextual and neuropsychological challenges of the adolescent period with particular attention to the role that universal prevention can play in moderating the harmful effects of stress. The centrality of emotion regulation skills to long-term health and wellness suggests their importance in prevention and intervention efforts for youth. Mindfulness has been shown to be an effective means of reducing stress and improving emotion balance in research with adults, although research on mindfulness with adolescents is limited. The authors present available data and describe one potentially effective program for adolescent mindfulness: Learning to BREATHE.


The efficacy of kinesiology taping for improving gross motor function in children with cerebral palsy: A systematic review.
Kinesiology taping is an increasingly popular technique used as an adjunct to physiotherapy intervention for children with cerebral palsy (CP), but as yet we do not have a review of the available evidence as to its efficacy. To critically appraise and establish best available evidence for the efficacy of truncal application of kinesiology taping combined with physiotherapy, versus physiotherapy alone, on gross motor function (GMF) in children with CP. Seven databases were searched using the terms CP, kinesio taping and/or kinesiology tape and/or taping, physiotherapy and/or physical therapy and GMF. Only randomised controlled trials (RCTs) were included and appraised using the PEDro scale. Revman© Review Manager was used to combine effects for GMF in sitting, standing and activities of daily living. Five level IIB RCTs that scored 3-6/8 on the PEDro scale were included. Meta-analysis showed that taping was effective for improving GMF in sitting and standing as measured by the Gross Motor Function Measure (B) (p < 0.001) and (D) (p < 0.001), respectively. There is moderate evidence to support kinesiology taping applied to the trunk as an effective intervention when used as an adjunct to physiotherapy to improve GMF in children with CP, especially those with GMF Classification Scale levels I and II, and particularly for improving sitting control. Kinesiology taping is a useful adjunct to physiotherapy intervention in higher functioning children with CP. Current evidence however is weak and further research into methods of truncal application is recommended.


H-Aggregates of an Indocyanine Cy5 Dye: Transition from Strong to Weak Molecular Coupling.
The aggregation behavior of an Indocyanine Cy5 dye (2-[5-[1,1-dimethyl-3-(4-sulfobutyl)-1,3-dihydro-benzo[e]indol-2-ylidene]-penta-1,3-dienyl]-1,1-dimethyl-3-(4-sulfobutyl)-1H-benzo[e]indolium hydroxide, inner salt, sodium salt) in aqueous solution is investigated using absorption and fluorescence spectroscopies, as well as cryogenic transmission electron microscopy (cryo-TEM). The dye concentration is varied within a broad range from ∼1 μM to ∼10 mM. At moderate concentrations, typical H-aggregates are formed. After longer storage time, the absorption spectra of these solutions change dramatically. The characteristic blue-shifted absorption band at around 600 nm becomes replaced by a three-banded absorption spectrum, which spreads over a wide wavelength range of ∼600 up to 800 nm. However, at the highest dye concentration and in the presence of ∼(10 to 30) mM NaCl, the three-banded spectrum is observed directly after preparation. The spectroscopic features can be ascribed to a structural transformation of strongly to weakly coupled H-type aggregates. The transformation is promoted by an increase of the ionic strength. Cryo-TEM data reveal that the weakly coupled H'-aggregates are organized in well-ordered, extended monolayer sheets, whereas the strongly coupled H-aggregates appear to consist of particles of only a few nanometers in size.


Interest in Over-the-Counter Access to a Progestin-Only Pill among Women in the United States.
A progestin-only pill may be the first pill formulation to become available over the counter in the United States; however, no research on over-the-counter (OTC) pill interest has focused on progestin-only pills or a representative sample of teens. The objective of this study was to assess U.S. women and teens' interest in OTC progestin-only pill use. In October 2015, we conducted a nationally representative, cross-sectional, online survey with 2,026 sexually active adult women aged 18 to 44 not currently desiring pregnancy, and 513 female teens aged 15 to 17. Logistic regression was used to identify characteristics associated with likely OTC progestin-only pill use. We also assessed reasons for use or nonuse, duration of use, and willingness to pay. Thirty-nine percent of adults and 29% of teens reported likely use, with a greater likelihood if covered by insurance. Adults were willing to pay $15 per month and teens $10 per month on average. Among adults, women who were never married or living alone (vs. married), uninsured (vs. privately insured), current pill or less effective method users (vs. ring, patch, injectable, or intrauterine device), tried to get a birth control prescription in the past year, or ever used an oral contraceptive pill or progestin-only pill had higher odds of likely use. Among teens, Spanish speakers and those who ever had sex had higher odds of likely use; Black teens (vs. White) had lower odds. Teens and adults are interested in using an OTC progestin-only pill. These findings indicate a large pool of interested users and the potential for improved contraceptive access by making an OTC progestin-only pill available.


Two-way signalling through the LFA-1 lymphocyte adhesion receptor.
T lymphocyte recognition of foreign antigens and migration throughout the body require the regulated adhesion of lymphocytes to diverse types of cells and to the extracellular matrix. The lymphocyte adhesion 'receptor' LFA-1, a member of the integrin family, interacts with ICAM-1 and other counter-receptors to mediate adhesion. The LFA-1/ICAM-1 interaction is regulated by signals transmitted from the cytoplasm to the extracellular space. Conversely, LFA-1 transmits signals from the extracellular space to the cytoplasm to regulate T lymphocyte activation. The observed properties of LFA-1 and related adhesion 'receptors' are incorporated into a general model for adhesion during immune surveillance and recognition of foreign antigens.


Understanding structural brain changes in schizophrenia.
Schizophrenia is a chronic progressive disorder that has at its origin structural brain changes in both white and gray matter. It is likely that these changes begin prior to the onset of clinical symptoms in cortical regions, particularly those concerned with language processing. Later, they can be detected by progressive ventricular enlargement. Current magnetic resonance imaging (MRI) technology can provide a valuable tool for detecting early changes in cortical atrophy and anomalous language processing, which may be predictive of who will develop schizophrenia.


Identifying cytochrome p450 functional networks and their allosteric regulatory elements.
Cytochrome P450 (CYP) enzymes play key roles in drug metabolism and adverse drug-drug interactions. Despite tremendous efforts in the past decades, essential questions regarding the function and activity of CYPs remain unanswered. Here, we used a combination of sequence-based co-evolutionary analysis and structure-based anisotropic thermal diffusion (ATD) molecular dynamics simulations to detect allosteric networks of amino acid residues and characterize their biological and molecular functions. We investigated four CYP subfamilies (CYP1A, CYP2D, CYP2C, and CYP3A) that are involved in 90% of all metabolic drug transformations and identified four amino acid interaction networks associated with specific CYP functionalities, i.e., membrane binding, heme binding, catalytic activity, and dimerization. Interestingly, we did not detect any co-evolved substrate-binding network, suggesting that substrate recognition is specific for each subfamily. Analysis of the membrane binding networks revealed that different CYP proteins adopt different membrane-bound orientations, consistent with the differing substrate preference for each isoform. The catalytic networks were associated with conservation of catalytic function among CYP isoforms, whereas the dimerization network was specific to different CYP isoforms. We further applied low-temperature ATD simulations to verify proposed allosteric sites associated with the heme-binding network and their role in regulating metabolic fate. Our approach allowed for a broad characterization of CYP properties, such as membrane interactions, catalytic mechanisms, dimerization, and linking these to groups of residues that can serve as allosteric regulators. The presented combined co-evolutionary analysis and ATD simulation approach is also generally applicable to other biological systems where allostery plays a role.


An audit of influenza vaccination status in adults with inflammatory bowel disease.
Several guidelines recommend influenza vaccination for high-risk patients, including those on immune-suppressing medications (IS). To assess the vaccination status and immunization history of an outpatient inflammatory bowel disease (IBD) population for H1N1 and seasonal influenza. Among 250 patients, 104 (41.6%) had been immunized against H1N1 and 62 (24.8%) against seasonal influenza, and 158 (63.2%) were taking IS (azathioprine, 6-mercaptopurine, infliximab, adalimumab, methotrexate, cyclosporine or prednisone). Among subjects on IS, the presence of comorbidities warranting vaccination was associated with higher likelihood of H1N1 immunization (62.5% versus 35.8%; P=0.022) but not of seasonal influenza vaccination (25.0% versus 17.2%; P=0.392). Among patients without comorbidities warranting vaccination, IS was associated with a decreased likelihood of vaccination against seasonal influenza (17.2% versus 30.7%; P=0.036) but not H1N1 (35.8% versus 41.3%; P=0.46). The frequency of H1N1 vaccination was significantly higher among patients who visited a general practitioner at least once yearly (45.7% versus 20%; P=0.0027), with a similar trend for seasonal influenza vaccination (27.1% versus 12.5%; P=0.073). Among 91 patients on IS who declined vaccination, 39.6% reported fear of immediate side effects, 29.7% reported concerns about developing serious medical complications, 15.4% reported concerns about activating IBD and 15.4% were not aware that vaccination was indicated. Current strategies for vaccinating IBD patients on IS are inadequate. Primary care provider education, incentive programs and regular primary care contact may improve immunization uptake.


2,000 Steps/Day Does Not Fully Protect Skeletal Muscle Health in Older Adults During Bed Rest.
Physical activity in an inpatient setting is often limited to brief periods of walking. For healthy adults, public health agencies recommend a minimum of 150 min/week of moderate-intensity exercise. The authors sought to determine if meeting this activity threshold, in the absence of incidental activities of daily living, could protect skeletal muscle health during bed rest. Healthy older adults (68 ± 2 years) were randomized to 7-day bed rest with (STEP, n = 7) or without (CON, n = 10) a 2,000 steps/day intervention. Performing 2018 ± 4 steps/day did not prevent the loss of lean leg mass and had no beneficial effect on aerobic capacity, strength, or muscle fiber volume. However, the insulin response to an oral glucose challenge was preserved. Performing a block of 2,000 steps/day, in the absence of incidental activities of daily living, was insufficient to fully counter the catabolic effects of bed rest in healthy older adults.