Characteristics of Auditory Processing Disorders: A Systematic Review.
The purpose of this review article is to describe characteristics of auditory processing disorders (APD) by evaluating the literature in which children with suspected or diagnosed APD were compared with typically developing children and to determine whether APD must be regarded as a deficit specific to the auditory modality or as a multimodal deficit. Six electronic databases were searched for peer-reviewed studies investigating children with (suspected) APD in comparison with typically developing peers. Relevant studies were independently reviewed and appraised by 2 reviewers. Methodological quality was quantified using the American Speech-Language-Hearing Association's levels of evidence. Fifty-three relevant studies were identified. Five studies were excluded because of weak internal validity. In total, 48 studies were included, of which only 1 was classified as having strong methodological quality. Significant dissimilarities were found between children referred with listening difficulties and controls. These differences relate to auditory and visual functioning, cognition, language, reading, and physiological and neuroimaging measures. Methodological quality of most of the incorporated studies was rated moderate due to the heterogeneous groups of participants, inadequate descriptions of participants, and the omission of valid and reliable measurements. The listening difficulties of children with APD may be a consequence of cognitive, language, and attention issues rather than bottom-up auditory processing.


WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility.
Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call "α-motility." Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE-activators of branched actin assembly-make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP's role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin.


Short-term variations in response distribution to cortical stimulation.
Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change occurring at a given location with stimulation would help predict the distribution of responses elsewhere over the cortex to stimulation at that given location. We did this by studying cortical afterdischarges following electrical stimulation of the cortex in awake humans undergoing evaluations for brain surgery. Response occurrence and location could change within seconds, both nearby to and distant from stimulation sites. Responses might occur at a given location during one trial but not the next. They could occur at electrodes adjacent or not adjacent to those directly stimulated or to other electrodes showing afterdischarges. The likelihood of an afterdischarge at an individual site after stimulation was predicted by spontaneous electroencephalographic activity at that specific site just prior to stimulation, but not by overall cortical activity. When stimulation at a site interrupted motor, sensory or language function, afterdischarges were more likely to occur at other sites where stimulation interrupted similar functions. These results show that widespread dynamic changes in cortical responses can occur in intact cortex within short periods of time, and that the distribution of these responses depends on local brain states and functional brain architecture at the time of stimulation. Similar rapid variations may occur during normal intracortical communication and may underlie changes in the cortical organization of function. Possibly these variations, and the occurrence and distribution of responses to cortical stimulation, could be predicted. If so, interventions such as stimulation might be used to alter spread of epileptogenic activity, accelerate learning or enhance cortical reorganization after brain injury.


Robust rotation-invariant texture classification using a model based approach.
In this paper, a model based texture classification procedure is presented. The texture is modeled as the output of a linear system driven by a binary image. This latter retains the morphological characteristics of the texture and it is specified by its spatial autocorrelation function (ACF). We show that features extracted from the ACF of the binary excitation suffice to represent the texture for classification purposes. Specifically, we employ a moment invariants based technique to classify the ACF. The resulting proposed classification procedure is thus inherently rotation invariant. Moreover, it is robust with respect to additive noise. Experimental results show that this approach allows obtaining high correct rotation-invariant classification rates while containing the size of the feature space.


The EGF receptor system in head and neck carcinomas and normal tissues. Immunohistochemical and quantitative studies.
The EGF receptor (EGF receptor) and two of the ligands, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF), exert mitogenic activities in epithelial cells. Hence, the overall aim of this work was delineation of the EGF receptor system in head and neck carcinomas, which in the majority of cases are epithelial derived tumours. Chapter 1 is a general introduction to head and neck carcinomas and the relevance of the EGF receptor system in this context. Chapter 2 focuses on the immunohistochemical distribution of TGF-alpha in normal human tissues, while previous studies dealing with the growth factor in head and neck carcinomas revealed other localizations in normal cells. TGF-alpha was detected with monoclonal as well as polyclonal antibodies. The results showed that the growth factor is widely distributed in normal human tissues and thus not limited to malignant cells. Chapter 3 describes the immunohistochemical localization of the EGF receptor in 55 patients with squamous cell carcinoma in the head and neck region. The study included adjacent normal mucosa and in 12 cases additional dysplastic areas were present. The EGF receptor was found in the basal cell layer in normal oral and laryngeal mucosa. In sections from patients who had received preoperative irradiation the receptor was in addition seen on the spinous cells. In dysplastic epithelial all cells stained for the EGF receptor. The majority of the head and neck carcinomas expressed the EGF receptor. In poorly differentiated tumours almost all cells were positive for the receptor. Sections from moderately and well differentiated tumours demonstrated a reduction in the extent of stained areas, paralleling the situation observed in the differentiated upper layers of normal oral and laryngeal mucosa. Furthermore, this chapter describes the EGF receptor quantitatively in 60 patients with head and neck carcinoma. This study was performed in order to evaluate if overexpression of the EGF receptor was a common motif for head and neck carcinomas. The level in tumour biopsies was compared with the level in the patients' corresponding normal mucosa. An enzyme-linked immunosorbent assay detecting protein epitopes of the receptor was employed. Overexpression of the receptor was found in the majority of cases. The overexpression was further correlated to clinicopathological parameters. However, no significant correlations were found although the mean values increased with increased tumour size and advanced clinical stage. The use of quantitative assays are further discussed and limitations are emphasized with respect to heterogeneity at the EGF receptor level and the varying stromal components in malignant tissues. Despite these problems the relevance of the EGF receptor a therapeutic situation is illustrated with e.g. EGF receptor antibodies and tyrosine-kinase inhibitors. Chapter 4 focuses on the immunohistochemical expression of EGF and TGF-alpha in carcinomas from same 55 patients. This study included adjacent normal mucosa in which the growth factors were expressed above the basal cell layer. The majority of the tumours expressed both growth factors and none of the sections were negative for both EGF and TGF-alpha. In biopsies from moderately and well differentiated tumours the growth factors were demonstrated in the more differentiated cells. However, in poorly differentiated tumours the cells were positive for EGF and TGF-alpha. Chapter 5 describes immunohistochemical and quantitative changes of salivary EGF, amylase and haptocorrin following radiotherapy for oral cancer. This study was initiated because irradiated oral and laryngeal mucosa have demonstrated staining for the receptor in the basal cell layer as well as in the spinous cells, indicating an upregulation of the receptor in response to lack of EGF. In normal biopsies from the glandula submandibularis and glandula parotis, EGF and amylase were demonstrated in the serous acini, whereas haptoc


A pilot study analyzing the effects of Chinese cupping as an adjunct treatment for patients with subacute low back pain on relieving pain, improving range of motion, and improving function.
Cupping, a classic Chinese medicine treatment, is a technique that applies suction cups over soft tissue. Cupping is gaining popularity in physical medicine because of the simplicity in application, minimal adverse effects, and reduction in pain and muscle tenderness. These factors also make it a cost-effective intervention. For this study, cupping was used to treat low back pain (LBP). To evaluate the effectiveness of Chinese cupping in acutely reducing pain, decreasing tenderness to palpation, and improving range of motion for patients with subacute or chronic LBP. Twenty-one patients who reported back pain for at least 8 weeks volunteered at a multidisciplinary holistic outpatient clinic. After completion of a medical screening questionnaire and collection of baseline data, 4 glass cups were applied and pressurized over the lower erector spinae muscles. Baseline data included demographic characteristics and the Oswestry Disability Questionnaire score. Pre- and postintervention data included perceived pain on a visual analog scale (VAS), lumbar spine range of motion, straight-leg raise test (SLR), and pain-pressure threshold (PPT) assessed with a digital force gauge. The data were analyzed by using a Wilcoxon signed-rank test and Spearman rho correlations. Of the 17 patients who completed the study, there were significant post-treatment improvements in VAS scores (p=0.0001), SLR motion on the left (p=0.043), and lumbar flexion range of motion (p=0.016) and improvements in PPT at all 4 investigated points (p<0.007). Significant relationships were identified between the improvement in low back flexion with the improvement in PPT at bilateral lumbar paraspinal muscles at the L4 levels and at the left L2 level. Chinese cupping may be a low-risk, therapeutic treatment for the prompt reduction of symptoms associated with subacute and chronic low back pain. Cupping may allow patients to progress to functional movement training in a timely manner by promptly reducing pain and muscle tenderness and improving range of motion.


Quantification of stromal destruction in the inflamed cornea.
An intrastromal injection of endotoxin lipopolysaccharide (LPS) in one eye of New Zealand albino rabbits induced a prominent keratitis characterized clinically and microscopically by edema and infiltration. Polymorphonuclear leukocytes (PMNs) constituted the primary invading leukocytic element. Collagen synthesis was measured by pulsing the corneas with 3H-proline before inducing inflammation. The invasion of the cornea by leukocytes did not alter the conversion of proline to hydroxyproline significantly in the stroma during the 14-day observation period, signifying that there were only negligible changes in the rate of collagen synthesis. However, the percentage of total stromal protein represented by collagen (ie, collagen/total protein) was only 50% of that in comparable corneas receiving an injection of phosphate-buffered saline. Some animals were rendered leukopenic by intravenous nitrogen mustard before intrastromal LPS injection caused a less severe corneal inflammatory response, characterized microscopically by fewer infiltrating leukocytes. Similarly, in nonleukopenic rabbits, topical therapy with 1% prednisolone acetate markedly reduced the corneal inflammatory response which also was characterized by fewer invading leukocytes. In neither instance was there extreme collagen loss, suggesting that the loss of stromal collagen is related to PMN infiltration.


Measles outbreak response decision-making under uncertainty: a retrospective analysis.
Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996-1997 measles outbreak in São Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination.


Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome.
Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-gamma ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-gamma concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-gamma contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought.


Assessing access to care under Medicaid: evidence for the nation and thirteen states.
States have broad latitude in designing their Medicaid programs; this has important implications for access to care. To understand the consequences of state variation, we evaluate, for the nation and for thirteen study states, how well the program is providing access for beneficiaries, using the level of access available to low-income privately insured people in the local health care market as our benchmark. Overall, we find that Medicaid beneficiaries' access matches that of the low-income privately insured for most of the ambulatory outcomes examined but is worse for dental services and prescription drugs. State-level analyses revealed some variation in the access gap.


Temperature sensitivity of phospho-Ser(473)-PKB/AKT.
The phospho-PKB/Akt status is often used as surrogate marker to measure activation of the PI3K/Akt/mTOR signal transduction pathway. Though, inconsistencies of the p-Ser(473)-PKB/Akt status have raised doubts in the validity of p-Ser(473)-PKB/Akt phosphorylation as endpoint. Here, we determined that p-Ser(473)-PKB/Akt but not p-Thr(308)-PKB/Akt phosphorylation is highly temperature sensitive. p-Ser(473)-PKB/Akt phosphorylation was rapidly reduced to levels below 50% on exposure to 20-25 degrees C in murine and human cell lines including cells expressing constitutively active PI3K or lacking PTEN. Down-regulation of p-Ser(473)-PKB/Akt was reversible and re-exposure to physiological temperature resulted in increased p-Ser(473)-PKB/Akt phosphorylation levels. Phosphatase activity at low temperature was sustained at 75% baseline level and phosphatase inhibition prevented p-Ser(473)-PKB/Akt dephosphorylation induced by the low temperature shift. Interestingly temperature-dependent deregulation of the p-Ser(473)-PKB/Akt status was also observed in response to irradiation. Thus our data demonstrate that minimal additional stress factors deregulate the PI3K/Akt-survival pathway and the p-Ser(473)-PKB/Akt status as experimental endpoint.


High SMAD4 levels appear in microsatellite instability and hypermethylated colon cancers, and indicate a better prognosis.
Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study, we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. Four hundred and seventy-nine paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, however, was significantly associated with increased survival, especially in colon cancer patients, which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.


Childhood obesity: trends and potential causes.
The increase in childhood obesity over the past several decades, together with the associated health problems and costs, is raising grave concern among health care professionals, policy experts, children's advocates, and parents. Patricia Anderson and Kristin Butcher document trends in children's obesity and examine the possible underlying causes of the obesity epidemic. They begin by reviewing research on energy intake, energy expenditure, and "energy balance," noting that children who eat more "empty calories" and expend fewer calories through physical activity are more likely to be obese than other children. Next they ask what has changed in children's environment over the past three decades to upset this energy balance equation. In particular, they examine changes in the food market, in the built environment, in schools and child care settings, and in the role of parents-paying attention to the timing of these changes. Among the changes that affect children's energy intake are the increasing availability of energy-dense, high-calorie foods and drinks through schools. Changes in the family, particularly an increase in dual-career or single-parent working families, may also have increased demand for food away from home or pre-prepared foods. A host of factors have also contributed to reductions in energy expenditure. In particular, children today seem less likely to walk to school and to be traveling more in cars than they were during the early 1970s, perhaps because of changes in the built environment. Finally, children spend more time viewing television and using computers. Anderson and Butcher find no one factor that has led to increases in children's obesity. Rather, many complementary changes have simultaneously increased children's energy intake and decreased their energy expenditure. The challenge in formulating policies to address children's obesity is to learn how best to change the environment that affects children's energy balance.


Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease.
Recent data in mice have identified de novo ceramide synthesis as the key mediator of hepatic insulin resistance (IR) that in humans characterizes increases in liver fat due to IR ('Metabolic NAFLD' but not that due to the I148M gene variant in PNPLA3 ('PNPLA3 NAFLD'). We determined which bioactive lipids co-segregate with IR in the human liver. Liver lipidome was profiled in liver biopsies from 125 subjects that were divided into equally sized groups based on median HOMA-IR ('High and Low HOMA-IR', n=62 and n=63) or PNPLA3 genotype (PNPLA3(148MM/MI), n=61 vs. PNPLA3(148II), n=64). The subjects were also divided into 4 groups who had either IR, the I148M gene variant, both of the risk factors or neither. Steatosis and NASH prevalence were similarly increased in 'High HOMA-IR' and PNPLA3(148MM/MI) groups compared to their respective control groups. The 'High HOMA-IR' but not the PNPLA3(148MM/MI) group had features of IR. The liver in 'High HOMA-IR' vs. 'Low HOMA-IR' was markedly enriched in saturated and monounsaturated triacylglycerols and free fatty acids, dihydroceramides (markers of de novo ceramide synthesis) and ceramides. Markers of other ceramide synthetic pathways were unchanged. In PNPLA3(148MM/MI)vs. PNPLA3(148II), the increase in liver fat was due to polyunsaturated triacylglycerols while other lipids were unchanged. Similar changes were observed when data were analyzed using the 4 subgroups. Similar increases in liver fat and NASH are associated with a metabolically harmful saturated, ceramide-enriched liver lipidome in 'Metabolic NAFLD' but not in 'PNPLA3 NAFLD'. This difference may explain why metabolic but not PNPLA3 NAFLD increases the risk of type 2 diabetes and cardiovascular disease.


Could public restrooms be an environment for bacterial resistomes?
Antibiotic resistance in bacteria remains a major problem and environments that help to maintain such resistance, represent a significant problem to infection control in the community. Restrooms have always been regarded as potential sources of infectious diseases and we suggest they have the potential to sustain bacterial "resistomes". Recent studies have demonstrated the wide range of different bacterial phyla that can be found in non-healthcare restrooms. In our study we focused on the Staphylococci. These species are often skin contaminants on man and have been reported as common restroom isolates in recent molecular studies. We collected samples from 18 toilets sited in 4 different public buildings. Using MALDI-TOF-MS and other techniques, we identified a wide range of antibiotic resistant Staphylococci and other bacteria from our samples. We identified 19 different Staphylococcal species within our isolates and 37.8% of the isolates were drug resistant. We also identified different Staphylococcal species with the same antibiograms inhabiting the same restrooms. Bacterial "resistomes" are communities of bacteria often localised in specific areas and within these environments drug resistance determinants may be freely transferred. Our study shows that non-healthcare restrooms are a source of antibiotic resistant bacteria where a collection of antibiotic resistance genes in pathogenic and non-pathogenic bacteria could form a resistome containing a "nexus of genetic diversity"


One-Year Results of Stab Incision Glaucoma Surgery and Radiofrequency-Assisted Stab Incision in Management of Open-Angle Glaucoma.
The aim of the study is to evaluate the surgical outcome of stab incision glaucoma surgery (SIGS) and compare it with radiofrequency-assisted stab incision in the treatment of uncontrolled open-angle glaucoma. A prospective, interventional study included 50 eyes who were assigned into two equal groups: Group A underwent stab incision procedure with preoperative subconjunctival (SC) mitomycin-C (MMC) and Group B underwent radiofrequency-assisted technique without MMC. Intraoperative and postoperative complications, visual acuity, intraocular pressure (IOP), and bleb status were evaluated up to 12 months. Mean preoperative IOP in Group A was 26.96 ± 2.42 reduced to 13.43 ± 2.31 while in Group B was 27.20 ± 3.57 reduced to 15.48 ± 3.68 mmHg (P < 0.001) with a mean reduction of 50.61% ± 8.42% and 43.56% ± 12.83%, 12 months postoperatively in Groups A and B, respectively. Non-basal peripheral iridectomy was the most encountered intraoperative complication in 8 eyes (32%) and 9 eyes (36%) and hypotony was the most reported postoperative complication in 5 eyes (20%) and 9 eyes (36%) in Groups A and B, respectively. Flat bleb area had been reported at the end of follow-up time in 3 eyes (13%) and 7 eyes (30%) in Groups A and B, respectively. Complete success rate was 52.2% and 28.6% while qualified success rate was 28.8% and 42.9% in Groups A and B, respectively. SIGS with SC MMC is an effective and safe procedure in IOP lowering, while radiofrequency-assisted stab incision had high incidence of subconjunctival scarring and ostium closure.


5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action.
Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown. We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design. Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions. Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations.


The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.
Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care.


The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births.
Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26 weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.


Acute effect of alternating heavy and light resistances on power output during upper-body complex power training.
This study investigated the effect on upper-body power output of manipulating resistances during contrast or complex power training. This power-training strategy typically entails the athlete alternating sets of a heavy resistance in a strength-oriented exercise with sets of lighter resistances in a power-oriented exercise. Sixteen rugby league players, who were experienced in power training and who performed complex training on a regular basis, served as subjects for this study and were divided equally into a control (Con) or experimental (Exp) group. Both groups were pre- and posttested for power output while performing explosive bench press throws in a Smith machine with a resistance of 50 kg (BT P50). The Exp group performed an intervention strategy of a 6-repetition set of bench presses with a resistance of 65% of 1 repetition maximum (65% 1RM) between tests. At the pretest occasion, no differences were observed between the groups in power output; however, at the posttesting, a significant difference in power output was observed between the groups in the BT P50. The 4.5% increase in the power output recorded during the posttesting BT P50 for the Exp group was determined to be significantly different from all other scores (p < or = 0.05). These data indicate that the performance of a set of heavy resistance strength training exercise between power training sets will acutely enhance power output in the second power training set. This effect has been previously theorized as possibly due to some combination of acute neural or mechanical adaptations.


Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome, and mtDNA markers.
The present Venezuelan population is the product of admixture of Amerindians, Europeans, and Africans, a process that was not homogeneous throughout the country. Blood groups, short tandem repeats (STRs), mtDNA, and Y-chromosome markers have been used successfully in admixture studies, but few such studies have been conducted in Venezuela. In this study we aim to estimate the admixture components of samples from two different socioeconomic levels from Caracas, Venezuela's capital city, compare their differences, and infer sexual asymmetry in the European Amerindian union patterns. Gene frequencies for blood groups ABO and Rh (CDE) and for the STRs VWA, F13A01, and FES/FPS and mtDNA and Y-chromosome haplogroups were studied in a sample of 60 individuals living in Caracas, taken from a private clinic (high socioeconomic level), and 50 individuals, also living in Caracas, drawn from a public maternity clinic (low socioeconomic level). The admixture analysis for the five autosomal markers gives a high European component (0.78) and an almost negligible African sub-Saharan component (0.06) for the high socioeconomic level, whereas for the low socioeconomic level the sub-Saharan, European, and Amerindian components were 0.21, 0.42, and 0.36, respectively. Estimates of admixture based on mtDNA and Y-chromosome markers reveal that the Amerindian contribution to these Caracas samples is almost entirely through females, because the Y-chromosome Amerindian and African sub-Saharan chromosomes found in this study were scarce. Our study reveals that the identification of the grandparents' geographic origin is an important methodological aspect to take into account in genetic studies related to the reconstruction of historical events.


The Role of Acupuncture in the Management of Insomnia as a Major or Residual Symptom Among Patients With Active or Previous Depression: A Systematic Review and Meta-Analysis.
Due to concerns about risks associated with antidepressants and/or hypnotics, complementary therapies such as acupuncture have been sought by patients with active or previous depression to manage insomnia. This systematic review aimed to clarify if acupuncture is effective and safe enough to be recommended as an alternative or adjuvant therapy to standard care in ameliorating concomitant or residual insomnia, two types of insomnia associated with depression. Randomized controlled trials (RCTs) of depression-related insomnia (DI) treatment via acupuncture vs. waitlist-control or placebo-/sham-acupuncture and RCTs of DI treatment via acupuncture alone or combined with standard care [Western pharmacotherapy and/or cognitive-behavioral therapy (CBT)] vs. standard care alone were searched for from seven databases from inception to December 2021. Cochrane criteria were followed. Twenty-one studies involving 1,571 participants were analyzed. For insomnia as a major symptom of active depression, meta-analyses suggested that acupuncture significantly reduced the global scores of both the Pittsburg Sleep Quality Index (PSQI) [MD = -3.12, 95% CI (-5.16, -1.08), p < 0.01] and Hamilton Depression Scale (HAMD) [SMD = -2.67, 95% CI (-3.51, -1.84), p < 0.01], in comparison with placebo-acupuncture. When compared with conventional pharmacotherapy (antidepressants and/or hypnotics), the results favored acupuncture in decreasing PSQI [MD = -1.17, 95% CI (-2.26, -0.08), p = 0.03] and HAMD [SMD = -0.47, 95% CI (-0.91, -0.02), p = 0.04]. Acupuncture was comparable to conventional pharmacotherapy in reducing scores of each domain of PSQI. For insomnia as a residual symptom of previous or partially remitted depression, acupuncture conferred a very limited, non-significant therapeutic advantage against sham-/placebo-acupuncture. Whether acupuncture has an add-on effect to conventional pharmacotherapy in this type of insomnia has not been investigated. Also, no study was available to address the efficacy differences between acupuncture and CBT or the synergistic effect of these two therapies. There is a low to moderate level of evidence supporting acupuncture as a safe and effective remedy alternative to or adjuvant to conventional pharmacotherapy (antidepressant and/or hypnotic) in improving insomnia and other depression symptoms among patients with active depression. Furthermore, the patients' complaint of disrupted sleep continuity is most likely to benefit from acupuncture. The benefit of acupuncture on residual insomnia associated with previous or partially remitted depression is limited. Future acupuncture studies need to consider applying optimal dosage and addressing deficiencies in trial quality.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269880, PROSPERO, identifier: CRD42021269880.


[HYPERBARIC OXYGEN THERAPY- BASICS AND NEW APPLICATIONS].
Hyperbaric oxygen therapy (HBOT) serves as primary or adjunctive therapy for a diverse range of medical conditions. The indication for HBOT can be related to either pressure (decompression sickness or air emboli) or tissue hypoxia. It is now realized, that the combined action of hyperoxia and hyperbaric pressure, leads to significant improvement in tissue oxygenation while targeting both oxygen and pressure sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Clinical studies published in recent year's present convincing evidence that HBOT can be the coveted neurotherapeutic method for brain repair. Here we discuss the multi-faceted role of HBOT in wound care in general and in neurotherapeutics in detail. The recent evidence for HBOT efficacy in brain repair and the new understanding of brain energy management and response to damage opens new therapeutically fields that will be further investigated in the upcoming years.


Health-related quality of life in frail institutionalized elderly: effects of a cognition-action intervention and Tai Chi.
No previous studies have explored the effects of mind-body approaches on health-related quality of life (HRQoL) in the frail elderly. Cognition and action are an inseparable whole during functioning. Thus, a new intervention-based approach using familiarity-based movements and a nonjudgmental approach of "cognition-action" was proposed and was tested with Tai Chi on HRQoL in frail institutionalized elderly. Fifty-two participants (58% women) age 65-94 took part in a 24-wk Tai Chi (TC) intervention 4 days/wk or a cognition-action (CA) exercise program of 30 min twice a week. Changes in Mini Mental State score, physical (PCS) and mental component (MCS) summaries (SF12); Falls Efficacy Scale (FES); and exercise self-efficacy were explored. PCS improved from 33.6 +/- 6.7 to 51 +/- 4.8 in the TC group and from 30.6 +/- 9.9 to 45.1 +/- 10.2 in the CA group (p < .001). MCS of SF-12 (p < .001), FES (p < .001), and exercise self-efficacy (p < .01) were enhanced significantly in both groups. Adapted CA programs and Tai Chi were both efficient in improving HRQoL of frail elderly.


Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells.
CD8+ T cells require a signal through a costimulatory receptor in addition to TCR engagement to become activated. The role of CD28 in costimulating T cell activation is well established. NKG2D, a receptor found on NK cells, CD8+ alphabeta-TCR+ T cells, and gammadelta-TCR+ T cells, has also been implicated in T cell costimulation. In this study we have evaluated the role of NKG2D in costimulating mouse and human naive and effector CD8+ T cells. Unexpectedly, in contrast to CD28, NKG2D engagement by ligand or mAb is not sufficient to costimulate naive or effector CD8+ T cell responses in conventional T cell populations. While NKG2D did not costimulate CD8+ T cells on its own, it was able to modify CD28-mediated costimulation of human CD8+ T cells under certain contitions. It is, therefore, likely that NKG2D acts as a costimulatory molecule only under restricted conditions or requires additional cofactors.


Salts on Europa's surface detected by Galileo's near infrared mapping spectrometer. The NIMS Team.
Reflectance spectra in the 1- to 2.5-micrometer wavelength region of the surface of Europa obtained by Galileo's Near Infrared Mapping Spectrometer exhibit distorted water absorption bands that indicate the presence of hydrated minerals. The laboratory spectra of hydrated salt minerals such as magnesium sulfates and sodium carbonates and mixtures of these minerals provide a close match to the Europa spectra. The distorted bands are only observed in the optically darker areas of Europa, including the lineaments, and may represent evaporite deposits formed by water, rich in dissolved salts, reaching the surface from a water-rich layer underlying an ice crust.


Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors.
A library of 585 compounds built off a 7-azaindole core was evaluated for anti-HIV-1 activity, and ten hits emerged with submicromolar potency and therapeutic index >100. Of these, three were identified as non-nucleoside reverse transcriptase (RT) inhibitors and were assayed against relevant resistant mutants. Lead compound 8 inhibited RT with submicromolar potency (IC50=0.73μM) and also maintained some activity against the clinically important RT mutants K103N and Y181C (IC50=9.2, 3.5μM) in cell-free assays. Free energy perturbation guided lead optimization resulted in the development of a compound with a two-fold increase in potency against RT (IC50=0.36μM). These data highlight the discovery of a unique scaffold with the potential to move forward as next-generation anti-HIV-1 agents.


Otoacoustic emissions before and after listening to music on a personal player.
The problem of the potential impact of personal music players on the auditory system remains an open question. The purpose of the present study was to investigate, by means of otoacoustic emissions (OAEs), whether listening to music on a personal player affected auditory function. A group of 20 normally hearing adults was exposed to music played on a personal player. Transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), as well as pure tone audiometry (PTA) thresholds, were tested at 3 stages: before, immediately after, and the next day following 30 min of exposure to music at 86.6 dBA. We found no statistically significant changes in OAE parameters or PTA thresholds due to listening to the music. These results suggest that exposure to music at levels similar to those used in our study does not disturb cochlear function in a way that can be detected by means of PTA, TEOAE, or DPOAE tests.


The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled.
Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination.


Effects of tibial plateau angle and spacer thickness applied during in vitro canine total knee replacement on three-dimensional kinematics and collateral ligament strain.
To quantify the 3-D kinematics and collateral ligament strain of stifle joints in cadaveric canine limbs before and after cranial cruciate ligament transection followed by total knee replacement (TKR) involving various tibial plateau angles and spacer thicknesses. 6 hemi-pelvises collected from clinically normal nonchondrodystrophic dogs (weight range, 25 to 35 kg). Hemi-pelvises were mounted on a modified Oxford knee rig that allowed 6 degrees of freedom of the stifle joint but prevented mechanical movement of the hip and tarsal joints. Kinematics and collateral ligament strain were measured continuously while stifle joints were flexed. Data were again collected after cranial cruciate ligament transection and TKR with combinations of 3 plateau angles (0°, 4°, and 8°) and spacer thicknesses (5, 7, and 9 mm). Presurgical (ie, normal) stifle joint rotations were comparable to those previously documented for live dogs. After TKR, kinematics recorded for the 8°, 5-mm implant most closely resembled those of unaltered stifle joints. Decreasing the plateau angle and increasing spacer thickness altered stifle joint adduction, internal rotation, and medial translation. Medial collateral ligament strain was minimal in unaltered stifle joints and was unaffected by TKR. Lateral collateral ligament strain decreased with steeper plateau angles but returned to a presurgical level at the flattest plateau angle. Among the constructs tested, greatest normalization of canine stifle joint kinematics in vitro was achieved with the steepest plateau angle paired with the thinnest spacer. Furthermore, results indicated that strain to the collateral ligaments was not negatively affected by TKR.


Genome-Wide Mapping of Uncapped and Cleaved Transcripts Reveals a Role for the Nuclear mRNA Cap-Binding Complex in Cotranslational RNA Decay in Arabidopsis.
RNA turnover is necessary for controlling proper mRNA levels posttranscriptionally. In general, RNA degradation is via exoribonucleases that degrade RNA either from the 5' end to the 3' end, such as XRN4, or in the opposite direction by the multisubunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of cotranslational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames. This pattern of cotranslational degradation is especially evident near the ends of open reading frames, where we observe accumulation of cleavage events focused 16 to 17 nucleotides upstream of the stop codon because of ribosomal pausing during translation termination. Following treatment of Arabidopsis plants with the translation inhibitor cycloheximide, cleavage events accumulate 13 to 14 nucleotides upstream of the start codon where initiating ribosomes have been stalled with these sequences in their P site. Further analysis in xrn4 mutant plants indicates that cotranslational RNA decay is XRN4 dependent. Additionally, studies in plants lacking CAP BINDING PROTEIN80/ABA HYPERSENSITIVE1, the largest subunit of the nuclear mRNA cap binding complex, reveal a role for this protein in cotranslational decay. In total, our results demonstrate the global prevalence and features of cotranslational RNA decay in a plant transcriptome.


Healthy lifestyle and life expectancy free of major chronic diseases at age 40 in China.
Whether a healthy lifestyle helps achieve gains in life expectancy (LE) free of major non-communicable diseases and its share of total LE in Chinese adults remains unknown. We considered five low-risk lifestyle factors: never smoking or quitting for reasons other than illness, no excessive alcohol use, being physically active, healthy eating habits and healthy body fat levels. Here we show that after a median follow-up of 11.1 years for 451,233 Chinese adults, the LE free of cardiovascular diseases, cancer and chronic respiratory diseases (95% confidence interval) at age 40 years for individuals with all five low-risk factors was on average 6.3 (5.1-7.5) years (men) and 4.2 (3.6-5.4) years (women) longer than those with 0-1 low-risk factors. Correspondingly, the proportion of disease-free LE to total LE increased from 73.1% to 76.3% for men and from 67.6% to 68.4% for women. Our findings suggest that promoting healthy lifestyles could be associated with gains in disease-free LE in the Chinese population.


Intra-operative assessment of sentinel lymph node status by one-step nucleic acid amplification assay (OSNA) in early endometrial cancer: a prospective study.
Sentinel node mapping has been proposed to reduce surgical side effects, maintaining the accuracy in nodal status assessment for endometrial cancer. To investigate the role of one-step nucleic acid amplification assay (OSNA) analysis, in the intra-operative tailoring of full nodal dissection, and to analyze the correlation between the type of sentinel node metastasis and the risk of non-sentinel node metastasis. Surgical and pathological data were collected from 141 consecutive, clinical stage I patients with endometrial cancer undergoing surgical staging. Patients were excluded if they had previous pelvic or abdominal radiotherapy, chemotherapy, abdominal cancer, pelvic or abdominal lymphadenectomy, or contraindications to indocyanine green. All sentinel nodes were analyzed by OSNA, and full lymphadenectomy was performed in positive cases. Statistical analysis was performed using Χ2 and Fisher's exact test to determine whether any of these characteristics could accurately predict the non-sentinel nodes status in positive sentinel node patients. A total of 141 patients were included in the analysis. Bilateral sentinel nodes were identified in 104 (73.8%) patients, with a median number of 2 (range 2-6) sentinel nodes per patient. In the remaining 37 patients (26.2%), a unilateral sentinel node was obtained, with a median of 1 (range 1-3) sentinel node per patient. Thirty-three (12.0%) positive nodes were found in 24 (17.0%) patients: micro-metastases and macro-metastases were detected in 22 and 2 patients, respectively. At final pathology, all patients with positive non-sentinel nodes had macro-metastases in the sentinel node, whereas in micro-metastatic sentinel nodes no other positive nodes were found at full lymphadenectomy (p<0.001). Our results showed a correlation between the type of metastasis in the sentinel lymph node (SLN) and the incidence of positive non-SLNs. These data suggest a potential role of OSNA analysis in the surgical tailoring of patients with early endometrial cancer, with the goal of definitive risk stratification and a better individualization of adjuvant therapy.


Trends in HIV and AIDS based on HIV/AIDS surveillance data in Japan.
In recent years a decline in the number of new AIDS cases has been observed in several industrialized countries. It is important to know whether these recent trends observed in North America and Europe are also occurring in Japan. The number of people reported with HIV and AIDS by nationality, route of infection, and sex was calculated based on the HIV/AIDS surveillance data available in Japan through December 1997. The effect of reporting delay, which was defined as those HIV and AIDS cases reported in the calendar year following diagnosis, on the trends was examined. The coverage rate in reporting HIV cases was estimated as the ratio of the reported AIDS cases with prior report as an HIV-positive to the total number of reported AIDS cases. The cumulative number of reported cases of HIV among Japanese and non-Japanese residents of Japan up to the end of 1997 were 1,300 and 1,190, respectively. The cumulative number of reported cases of AIDS among Japanese and non-Japanese up to the end of 1997 were 758 and 298, respectively. The number of reported cases of HIV among Japanese was found to be still increasing, with the major contribution from male cases. The increasing trend in the number of reported AIDS cases among Japanese began to slow in 1996 and 1997. The number of reported cases of HIV among non-Japanese residents of Japan peaked in 1992, and has decreased since then, and remained constant after 1994. In contrast, the number of reported AIDS cases among these non-Japanese tended to increase gradually. There was a slight reporting delay for people with HIV and AIDS. The estimated coverage rate in reporting HIV cases tended to decrease in 1996 and 1997 (1/7.2, 1/10.2, respectively). We point out several reasons for this recent decline and suggest the possibility of an ostensible decline in the estimates. We suggest that the number of people with HIV among Japanese has continued to increase, and that the increase in the number of AIDS cases among Japanese is now slowing.


Colon cancer and enterococcus bacteremia co-affection: A dangerous alliance.
Adenocarcinoma of the colorectal region is one of the leading causes of cancer-related mortality in the USA and hence an important public health concern. Enterococci are emerging as an important cause of infection in the elderly. While translocation of enteric bacteria into the bloodstream is a known phenomenon in patients with infectious, inflammatory or infiltrative conditions of the bowel, a causative link between Enterococcus bacteremia and colorectal cancer has not been established in medical literature. We report the case of a patient presenting with E. faecalis bacteremia who was also diagnosed with infiltrating adenocarcinoma of the rectum. We discuss a possible relationship between these two conditions.


Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways.
Retinal ganglion cells (RGCs) innervate several specific CNS targets serving cortical and subcortical visual pathways and the entrainment of circadian rhythms. Recent studies have shown that retinal ganglion cells express specific combinations of POU- and LIM-domain transcription factors, but how these factors relate to the subsequent development of the retinofugal pathways and the functional identity of RGCs is mostly unknown. Here, we use targeted expression of an genetic axonal tracer, tau/beta-galactosidase, to examine target innervation by retinal ganglion cells expressing the POU-domain factor Brn3a. Brn3a is expressed in RGCs innervating the principal retinothalamic/retinocollicular pathway mediating cortical vision but is not expressed in RGCs of the accessory optic, pretectal, and hypothalamic pathways serving subcortical visuomotor and circadian functions. In the thalamus, Brn3a ganglion cell fibers are primarily restricted to the outer shell of the dorsal lateral geniculate, providing new evidence for the regionalization of this nucleus in rodents. Brn3a RGC axons have a relative preference for the contralateral hemisphere, but known mediators of the laterality of RGC axons are not repatterned in the absence of Brn3a. Brn3a is coexpressed extensively with the closely related factor Brn3b in the embryonic retina, and the effects of the loss of Brn3a in retinal development are not severe, suggesting partial redundancy of function in this gene class.


What to Do When K-Means Clustering Fails: A Simple yet Principled Alternative Algorithm.
The K-means algorithm is one of the most popular clustering algorithms in current use as it is relatively fast yet simple to understand and deploy in practice. Nevertheless, its use entails certain restrictive assumptions about the data, the negative consequences of which are not always immediately apparent, as we demonstrate. While more flexible algorithms have been developed, their widespread use has been hindered by their computational and technical complexity. Motivated by these considerations, we present a flexible alternative to K-means that relaxes most of the assumptions, whilst remaining almost as fast and simple. This novel algorithm which we call MAP-DP (maximum a-posteriori Dirichlet process mixtures), is statistically rigorous as it is based on nonparametric Bayesian Dirichlet process mixture modeling. This approach allows us to overcome most of the limitations imposed by K-means. The number of clusters K is estimated from the data instead of being fixed a-priori as in K-means. In addition, while K-means is restricted to continuous data, the MAP-DP framework can be applied to many kinds of data, for example, binary, count or ordinal data. Also, it can efficiently separate outliers from the data. This additional flexibility does not incur a significant computational overhead compared to K-means with MAP-DP convergence typically achieved in the order of seconds for many practical problems. Finally, in contrast to K-means, since the algorithm is based on an underlying statistical model, the MAP-DP framework can deal with missing data and enables model testing such as cross validation in a principled way. We demonstrate the simplicity and effectiveness of this algorithm on the health informatics problem of clinical sub-typing in a cluster of diseases known as parkinsonism.


"She'll be right, mate!": do Australians take their health for granted?
INTRODUCTION Health consciousness highlights the readiness of individuals to undertake health actions and take responsibility for their health and the health of others. AIM To examine the health consciousness of Australians and its association with health status, health-care utilisation and sociodemographic factors. METHODS This quantitative cross-sectional study was a part of a larger project aiming to engage the general public in health-care decision-making. Adults from Queensland and South Australia (n=1529) were recruited to participate by a panel company. The questionnaire included the Health Consciousness Scale (HCS), health status, health-care utilisation, sociodemographic and socioeconomic variables. RESULTS The health consciousness of Australians was relatively low (mean score=21), compared to other international administrations of the HCS, and further investigations revealed that more health-conscious people tended to live in South Australia, be female and single, experience poorer physical and mental health and were more frequent users of health-care services. DISCUSSION The general approach to health in this sample of the Australian public may reflect 'here and now' concerns. It appears that an attitude of 'she'll be right, mate' prevails until a change in an individual's health status or their exposure to the health system demands otherwise. These findings need to be investigated further to see if they are confirmed by others and to clarify the implications for primary health programmes in Australia in redressing the public's apparent apathy.


Extremely low nucleotide polymorphism in Pinus krempfii Lecomte, a unique flat needle pine endemic to Vietnam.
Pinus krempfii Lecomte is a morphologically and ecologically unique pine, endemic to Vietnam. It is regarded as vulnerable species with distribution limited to just two provinces: Khanh Hoa and Lam Dong. Although a few phylogenetic studies have included this species, almost nothing is known about its genetic features. In particular, there are no studies addressing the levels and patterns of genetic variation in natural populations of P. krempfii. In this study, we sampled 57 individuals from six natural populations of P. krempfii and analyzed their sequence variation in ten nuclear gene regions (approximately 9 kb) and 14 mitochondrial (mt) DNA regions (approximately 10 kb). We also analyzed variation at seven chloroplast (cp) microsatellite (SSR) loci. We found very low haplotype and nucleotide diversity at nuclear loci compared with other pine species. Furthermore, all investigated populations were monomorphic across all mitochondrial DNA (mtDNA) regions included in our study, which are polymorphic in other pine species. Population differentiation at nuclear loci was low (5.2%) but significant. However, structure analysis of nuclear loci did not detect genetically differentiated groups of populations. Approximate Bayesian computation (ABC) using nuclear sequence data and mismatch distribution analysis for cpSSR loci suggested recent expansion of the species. The implications of these findings for the management and conservation of P. krempfii genetic resources were discussed.


Next-generation acceleration and code optimization for light transport in turbid media using GPUs.
A highly optimized Monte Carlo (MC) code package for simulating light transport is developed on the latest graphics processing unit (GPU) built for general-purpose computing from NVIDIA - the Fermi GPU. In biomedical optics, the MC method is the gold standard approach for simulating light transport in biological tissue, both due to its accuracy and its flexibility in modelling realistic, heterogeneous tissue geometry in 3-D. However, the widespread use of MC simulations in inverse problems, such as treatment planning for PDT, is limited by their long computation time. Despite its parallel nature, optimizing MC code on the GPU has been shown to be a challenge, particularly when the sharing of simulation result matrices among many parallel threads demands the frequent use of atomic instructions to access the slow GPU global memory. This paper proposes an optimization scheme that utilizes the fast shared memory to resolve the performance bottleneck caused by atomic access, and discusses numerous other optimization techniques needed to harness the full potential of the GPU. Using these techniques, a widely accepted MC code package in biophotonics, called MCML, was successfully accelerated on a Fermi GPU by approximately 600x compared to a state-of-the-art Intel Core i7 CPU. A skin model consisting of 7 layers was used as the standard simulation geometry. To demonstrate the possibility of GPU cluster computing, the same GPU code was executed on four GPUs, showing a linear improvement in performance with an increasing number of GPUs. The GPU-based MCML code package, named GPU-MCML, is compatible with a wide range of graphics cards and is released as an open-source software in two versions: an optimized version tuned for high performance and a simplified version for beginners (http://code.google.com/p/gpumcml).


Federalism, two-level games and the politics of abortion rights implementation in subnational Argentina.
The implementation of the 2012 Argentinean Supreme Court landmark ruling, which declared abortion legal in all cases of rape and established standards of implementation of lawful abortions at all levels of government, shows an uneven pattern of compliance by subnational governments throughout the country. Based on a case-study of the implementation of the Court's decision in the province of Salta, this article advances an explanation of mechanisms that can affect the definition and enforcement of abortion rights at the local level, in a federation. Drawing on Putnam's concept of two-level games, it argues that, at critical junctures, local authorities and especially strong governors with presidential aspirations, may have electoral incentives at the national level to comply at least partially with national laws and judicial decisions which are contrary to their own ideological preferences and their local political allegiances. The study suggests that analyses of political opportunities for local reproductive rights activists in federal regimes should include the potential two-level games of local authorities, such as politicians with presidential aspirations, and judges who intend to pursue a career in national or international institutions. Through this analysis, the article intends to contribute to our understanding of the political determinants of subnational compliance with national abortion laws and court decisions in federal systems, and more generally, political factors and dynamics that shape inequities in the protection of women's rights under federalism.


EPODE - A Model for Reducing the Incidence of Obesity and Weight-related Comorbidities.
Obesity is a global epidemic: it is estimated that the majority of the world's adults will be overweight or obese by 2030. It is therefore important to reverse trends towards increasing childhood obesity by interventions at the community level. Ensemble Prévenons l'obésité Des Enfants (EPODE, Together Let's Prevent Childhood Obesity) is a large-scale, coordinated, capacity-building approach for communities to implement effective and sustainable strategies to address this challenge. EPODE comprises four critical components: political commitment, public and private partnerships, community-based actions, and evaluation. The multi-stakeholder approach promoted through the EPODE methodology has already shown encouraging results in preventing childhood obesity in France and Belgium and has reduced the socioeconomic gap in obesity prevalence in France. The EPODE methodology has now been implemented in a number of countries worldwide, and provides a valuable model that may be applicable to other lifestyle-related diseases.


Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group.
Interleukin 10 (IL-10) is an anti-inflammatory, immunomodulatory cytokine that regulates mucosal inflammation. This study evaluated the safety, tolerance, and efficacy of recombinant human IL-10 (rhuIL-10) for mild to moderately active Crohn's disease. We conducted a 24-week multicenter, prospective, randomized, double-blind, placebo-controlled, and sequential-escalating-dose study. Ninety-five patients with Crohn's Disease Activity Index of 200-350, not presently undergoing corticosteroid, mesalamine, or immunosuppressive therapy, were treated with subcutaneous rhuIL-10 (1, 5, 10, or 20 microg/kg) or placebo once daily for 28 consecutive days. Patients were followed up for 20 weeks after treatment. Evaluation of safety and tolerance was the first objective, and efficacy was the second objective. Adverse effects were dose-related, mild-to-moderate in severity, and reversible. Asymptomatic and reversible anemia and thrombocytopenia were observed at higher doses. No withdrawal or delayed adverse effects were evident during 20 weeks of follow-up. At the end of treatment (day 29), intent-to-treat analysis showed that 23.5% (confidence interval [CI], 6.8%-49.9%) of patients receiving 5 micro/kg rhuIL-10 experienced clinical remission and endoscopic improvement; 0% (CI, 0%-14.8%) of patients in the placebo group did. Higher doses of recombinant human IL-10 were less effective than 5 microg/kg. No rhuIL-10 serum accumulation and no antibody against IL-10 were detected after 4 weeks. Subcutaneous rhuIL-10 administered daily for 28 days to patients with mild to moderately active Crohn's disease is safe, well-tolerated, and shows clinical and endoscopic improvement.


Stochasticity in natural forage production affects use of urban areas by black bears: implications to management of human-bear conflicts.
The rapid expansion of global urban development is increasing opportunities for wildlife to forage and become dependent on anthropogenic resources. Wildlife using urban areas are often perceived dichotomously as urban or not, with some individuals removed in the belief that dependency on anthropogenic resources is irreversible and can lead to increased human-wildlife conflict. For American black bears (Ursus americanus), little is known about the degree of bear urbanization and its ecological mechanisms to guide the management of human-bear conflicts. Using 6 years of GPS location and activity data from bears in Aspen, Colorado, USA, we evaluated the degree of bear urbanization and the factors that best explained its variations. We estimated space use, activity patterns, survival, and reproduction and modeled their relationship with ecological covariates related to bear characteristics and natural food availability. Space use and activity patterns were dependent on natural food availability (good or poor food years), where bears used higher human density areas and became more nocturnal in poor food years. Patterns were reversible, i.e., individuals using urban areas in poor food years used wildland areas in subsequent good food years. While reproductive output was similar across years, survival was lower in poor food years when bears used urban areas to a greater extent. Our findings suggest that bear use of urban areas is reversible and fluctuates with the availability of natural food resources, and that removal of urban individuals in times of food failures has the potential to negatively affect bear populations. Given that under current predictions urbanization is expected to increase by 11% across American black bear range, and that natural food failure years are expected to increase in frequency with global climate change, alternative methods of reducing urban human-bear conflict are required if the goal is to prevent urban areas from becoming population sinks.


Selective and superselective angiography of pediatric moyamoya disease angioarchitecture in the posterior circulation.
The anastomotic network of the posterior circulation in children with moyamoya disease has not been analyzed. We aimed to investigate the angiographic anatomy of this unique vascular network in patients with childhood moyamoya disease. Selective and superselective injections of the posterior circulation were performed in six children with newly diagnosed moyamoya disease. The arterial branches feeding the moyamoya anastomotic network, their connections and the recipient vessels were demonstrated. Depending on the level of the steno-occlusive lesion, the feeding vessels were the thalamoperforators, the posterior choroidals, the splenic artery, parietoccipital artery, other cortical posterior cerebral artery (PCA) branches, the dural branch of the PCA, the premamillary artery and other posterior communicating artery perforators. Through connections, which are described, the recipient vessels were the striate and medullary arteries, other thalamic arteries with or without medullary extensions, the pericallosal artery, medial parietoccipital cortical branches of the PCA and the anterior choroidal artery. High quality selective and superselective angiography helped in demonstrating the angiographic anatomy of the moyamoya posterior anastomotic network previously either vaguely or incompletely described, as well as connections within the posterior circulation but also its relevance as a collateral to the anterior circulation.


Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine-pyrimethamine and amodiaquine.
To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country. Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections. Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance. In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.


Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging.
Nanoscale liposomes have been extensively researched and employed clinically for the delivery of biologically active compounds, including chemotherapy drugs and vaccines, offering improved pharmacokinetic behaviour and therapeutic outcomes. Traditional laboratory-scale production methods often suffer from limited control over liposome properties (e.g., size and lamellarity) and rely on laborious multistep procedures, which may limit pre-clinical research developments and innovation in this area. The widespread adoption of alternative, more controllable microfluidic-based methods is often hindered by complexities and costs associated with device manufacturing and operation, as well as the short device lifetime and the relatively low liposome production rates in some cases. In this study, we demonstrated the production of liposomes comprising therapeutically relevant lipid formulations, using a cost-effective 3D-printed reactor-in-a-centrifuge (RIAC) device. By adjusting formulation- and production-related parameters, including the concentration of polyethylene glycol (PEG), temperature, centrifugation time and speed, and lipid concentration, the mean size of the produced liposomes could be tuned in the range of 140 to 200 nm. By combining selected experimental parameters, the method was capable of producing liposomes with a therapeutically relevant mean size of ~174 nm with narrow size distribution (polydispersity index, PDI ~0.1) at a production rate of >8 mg/min. The flow-through method proposed in this study has potential to become an effective and versatile laboratory-scale approach to simplify the synthesis of therapeutic liposomal formulations.


Cell-specific ablation of Hsp47 defines the collagen-producing cells in the injured heart
Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury–induced fibrosis theHsp47 gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion ofHsp47 from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of Hsp47; blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific Hsp47-deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of Hsp47reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of Hsp47 from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their proliferation in the heart without affecting paracrine secretory activity of these cells. The results show that myofibroblasts are the primary mediators of tissue fibrosis and scar formation in the injured adult heart, which unexpectedly affects cardiomyocyte hypertrophy.


Monolithic folded resonator for evanescent wave cavity ringdown spectroscopy.
An optical resonator is characterized that employs both ultrahigh-reflective coated surfaces and total internal reflection to enable cavity ringdown spectroscopy of surfaces, films, and liquids. The monolithic folded design possesses a polarization-independent finesse that allows polarization-dependent phenomena, such as molecular orientation, to be probed. Although a restricted bandwidth (~15% of the design wavelength) results from use of reflective coatings, the resonator provides high sensitivity and facile operation. A minimum detectable absorption of 2.2 x 10(-6) was obtained for single laser shots by use of multimode excitation at 530 nm with an excimer-pumped, pulsed dye laser.


National impact of pulsatile perfusion on cadaveric kidney transplantation.
The simplicity and success of cold storage of cadaveric kidneys have led to the infrequent use of pulsatile perfusion. However, there may be advantages to pulsatile perfusion for less optimal donors. United Network for Organ Sharing data were analyzed retrospectively to determine the impact of pulsatile perfusion on initial function and 1-year graft survival. The analysis included 60,827 cadaveric kidney transplants performed between 1988 and 1995. Multivariate logistic regression analyses were used to determine the effect of preservation method on both early kidney function (need for first-week dialysis after transplant) and 1-year graft survival, after adjusting for other known risk factors. The preservation method exhibited a highly significant impact on the need for first-week dialysis. Ice-preserved kidneys were associated with a 2.13-fold increase in the odds of requiring dialysis compared with perfused kidneys. If the donor age was > or =55 years, the odds were 2.33-fold higher for ice-preserved as compared with perfused. If cold ischemic time was > or =24 hr, there was a 2.19-fold increase in the odds of dialysis for ice-preserved kidneys. African-American recipients of cold-stored kidneys had a 2.29-fold greater odds of first-week dialysis. Based on these findings, it was estimated that the increased cost of perfusing kidneys from all donors > or =55 years of age would be balanced by the decreased need for posttransplant dialysis if the cost related to dialysis were $14,700 or greater per patient. These facts, coupled with the ability to assess an older donor kidney before transplant, could make pulsatile perfusion for the expanded donor financially as well as medically desirable.


Kinetics of the tissue distributions of sulindac and metabolites. Relevance to sites and rates of bioactivation.
Sulindac (sulfoxide) is a prodrug in reversible metabolic equilibrium with its pharmacologically active metabolite, the corresponding sulfide. Following simultaneous parenteral injection of sulfoxide-14C and sulfide-3H at equivalent dosage, all labeled species in the plasma of rats and guinea pigs and in representative tissues were determined at various times. Rate constants for sulfoxide in equilibrium or formed from sulfide, calculated from the rates of interchange of the two labels in plasma, are still higher than those approximated from earlier, single-label studies, and indicate turnovers of total body pools every 45 and 8.5 min in rat and guinea pig, respectively. From the time-course of tissue/plasma ratios of endogenous labeled species, it can be concluded that kidney and liver are major sites of bioactivation of the prodrug, with significant sulfoxide leads to sulfide activity present in all tissues examined. At steady state, tissue concentrations of each redox form are determined by the ratio of the metabolic rate constants for the two opposing biotransformations and by unique tissue/plasma distributive constants for each redox form, resulting in all tissues, except lung, and at all times examined, in a sulfide/sulfoxide ratio greater than one.


Violent and fatal youth trauma: is there a missed opportunity?
Accidents and assaults (homicides) are the leading causes of death among the youth of the United States, accounting for 53.3% of deaths among children aged 1 to19 years. Victim recidivism, defined as repeated visits to the emergency department (ED) as a victim of violent trauma, is a significantly growing public health problem. As 5-year mortality rates for recidivism are as high as 20%, it is important to determine whether victims with a history of violent trauma are at increased risk for fatal outcome with their next trauma. We hypothesized that victims of violent trauma who have had 1 prior ED visit for violent trauma will have increased odds of fatal outcome. A retrospective chart review was conducted for patients presenting with penetrating trauma to the ED from January 1, 1999 to December 31, 2009. All patients between the ages of 15 to 25 years who presented to the ED for any penetrating trauma were included. Patients with prior presentations for penetrating trauma were compared to those patients who were first-time presenters to determine the odds ratio of fatal outcome. Overall, 15,395 patients were treated for traumatic presentations. Of these, 1,044 met inclusion criteria. Demographically, 79.4% were Hispanic, 19.4% were African American, and 0.96% were Caucasian. The average age was 21 years, and 98% of the population was male. One hundred and forty-seven (14%) had prior presentations, and 897 (86%) did not. Forty of the 147 patients (27%) with prior presentations had a fatal outcome as compared to 29 patients of the 868 (3%) without prior presentations, with odds ratio of 10.8 (95% confidence interval, 6.4-18.1; Pearson χ(2), P < 0.001). The 5-year mortality rate for those patients with fatal outcomes was calculated at 16.5%. Patients who had prior ED visits for penetrating trauma were at greater risk for fatal outcomes compared to those with no prior visits. Therefore, trauma-related ED visits might offer an opportunity for education and intervention. This may help to prevent future fatalities.


Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography.
To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22-71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTT(A)), the tubular compartment (MTT(T)), and the collecting system compartment (MTT(C)) were calculated. Also derived was MTT for the whole kidney (MTT(K) = MTT(A) + MTT(T) + MTT(C)) and fractional MTT of each compartment (MTT(A/K) = MTT(A)/MTT(K), MTT(T/K) = MTT(T)/MTT(K), MTT(C/K) = MTT(C)/MTT(K)). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. There were significant differences in GFR and MTT(K) between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTT(A/K) was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTT(T/K) was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group (mean, 69.2% ± 6.1; P = .003). Low-dose MR renography analyzed by using a multicompartmental tracer kinetic renal model may help to differentiate noninvasively between acute rejection and ATN after kidney transplantation.


Tumour immune rejection triggered by activation of α2-adrenergic receptors.
Immunotherapy based on immunecheckpoint blockade (ICB) using antibodies induces rejection of tumours and brings clinical benefit in patients with various cancer types1. However, tumours often resist immune rejection. Ongoing efforts trying to increase tumour response rates are based on combinations of ICB with compounds that aim to reduce immunosuppression in the tumour microenvironment but usually have little effect when used as monotherapies2,3. Here we show that agonists of α2-adrenergic receptors (α2-AR) have very strong anti-tumour activity when used as monotherapies in multiple immunocompetent tumour models, including ICB-resistant models, but not in immunodeficient models. We also observed marked effects in human tumour xenografts implanted in mice reconstituted with human lymphocytes. The anti-tumour effects of α2-AR agonists were reverted by α2-AR antagonists, and were absent in Adra2a-knockout (encoding α2a-AR) mice, demonstrating on-target action exerted on host cells, not tumour cells. Tumours from treated mice contained increased infiltrating T lymphocytes and reduced myeloid suppressor cells, which were more apoptotic. Single-cell RNA-sequencing analysis revealed upregulation of innate and adaptive immune response pathways in macrophages and T cells. To exert their anti-tumour effects, α2-AR agonists required CD4+ T lymphocytes, CD8+ T lymphocytes and macrophages. Reconstitution studies in Adra2a-knockout mice indicated that the agonists acted directly on macrophages, increasing their ability to stimulate T lymphocytes. Our results indicate that α2-AR agonists, some of which are available clinically, could substantially improve the clinical efficacy of cancer immunotherapy.


Making Fe(BPBP)-catalyzed C-H and C[double bond, length as m-dash]C oxidations more affordable.
The limited availability of catalytic reaction components may represent a major hurdle for the practical application of many catalytic procedures in organic synthesis. In this work, we demonstrate that the mixture of isomeric iron complexes [Fe(OTf)2(mix-BPBP)] (mix-1), composed of Λ-α-[Fe(OTf)2(S,S-BPBP)] (S,S-1), Δ-α-[Fe(OTf)2(R,R-BPBP)] (R,R-1) and Δ/Λ-β-[Fe(OTf)2(R,S-BPBP)] (R,S-1), is a practical catalyst for the preparative oxidation of various aliphatic compounds including model hydrocarbons and optically pure natural products using hydrogen peroxide as an oxidant. Among the species present in mix-1, S,S-1 and R,R-1 are catalytically active, act independently and represent ca. 75% of mix-1. The remaining 25% of mix-1 is represented by mesomeric R,S-1 which nominally plays a spectator role in both C-H and C[double bond, length as m-dash]C bond oxidation reactions. Overall, this mixture of iron complexes displays the same catalytic profile as its enantiopure components that have been previously used separately in sp(3) C-H oxidations. In contrast to them, mix-1 is readily available on a multi-gram scale via two high yielding steps from crude dl/meso-2,2'-bipyrrolidine. Next to its use in C-H oxidation, mix-1 is active in chemospecific epoxidation reactions, which has allowed us to develop a practical catalytic protocol for the synthesis of epoxides.


Salivary gland involvement in graft-versus-host disease: the underlying mechanism and implicated treatment.
Patients with graft-versus-host disease suffer from xerostomia, oral infections and mucosal pathologies. The continuous increase in the number of patients treated with bone marrow transplants worldwide, combined with improved survival statistics result in a concomitant increase in the number of GVHD patients. The pathogenesis of GVHD is based on donor graft T lymphocytes that recognize antigenic disparities between donor and recipient, and on the disregulation of a broad panel of cytokines. Consequently, various tissues and organs, including the mucosa of the oral and gastrointestinal tract, are damaged via cytotoxicity caused by infiltrating T cells. Since the salivary glands are a known major target of GVHD and their secretions significantly contribute to preserving mucosal integrity, this mucosal insult is further enhanced by the reduced quantity and altered quality of saliva. GVHD occurs in 40-70% of patients treated by bone marrow and peripheral blood stem cell transplantation. Limited studies suggest that a large percentage of GVHD patients are affected and that the induced salivary dysfunction occurs rapidly following transplantation, affecting both major and minor salivary glands and reflecting the severity of the disease. Moreover, profound sialochemical alterations may be diagnostic of GVHD. An additional reason for the vast amount of research is that GVHD, as an autoimmune-like disease, seems to be an appropriate model for studying a much more prevalent, well-known and studied autoimmune disease involving salivary glands, namely, Sjögren's syndrome. The present review describes the GVHD-related sialometric and sialochemical data available in the literature for both major and minor salivary glands in both human and rodent models, and discusses a possible mechanism.


Anesthesia provider model, hospital resources, and maternal outcomes.
Determine the ability of anesthesia provider model and hospital resources to explain maternal outcome variation. 1,141,641 obstetrical patients from 369 hospitals that reported at least one live birth in 2002 in six representative states. Logistic regression of death, anesthesia complication, nonanesthesia maternal complication, and obstetrical trauma for all patients and those having cesarean deliveries on anesthesia provider model, obstetrical and anesthesia, and patient variables. Data was assembled from information given by hospitals to state agencies and from a 2004 survey of obstetrical organization resources. Anesthesia complication rates in anesthesiologist-only hospitals were 0.27 percent compared with 0.23 percent in certified registered nurse anesthetist (CRNA) only hospitals. Rates among other provider models varied from 0.24 to 0.37 percent with none statistically different from the anesthesiologist-only hospitals. A similar pattern was observed for rates of other outcomes. Multivariate analysis found no systematic differences between hospitals with anesthesiologist-only models and models using CRNAs. There was no consistent pattern of association of other hospital or patient characteristics with outcomes. Hospitals that use only CRNAs, or a combination of CRNAs and anesthesiologists, do not have systematically poorer maternal outcomes compared with hospitals using anesthesiologist-only models.


Transplantation of kidneys from DCD and DBD donors who died after ligature asphyxiation: The UK experience.
There is uncertainty about whether hypoxic injury accompanying donor death from ligature asphyxiation influences renal transplant outcomes, particularly for recipients of kidneys donated after circulatory death (DCD). The UK Registry analysis was undertaken to determine transplant outcomes in recipients of kidneys from donors who died following ligature asphyxiation. From 2003 to 2016, 2.7% (n = 521) of potential organ donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 409 (78.5%) donated kidneys for transplantation (46.9% donation after brain death [DBD] and 53.1% DCD donors) resulting in 650 kidney transplants. Compared to other deceased donors, those dying from ligature asphyxiation were younger, more often male, and had less hypertension. Unadjusted patient and graft survival were superior for recipients of both DBD and DCD kidneys from donors dying after ligature asphyxiation, although after adjustment for donor/recipient variables, transplant outcomes were similar. A case-control matched analysis confirmed transplant outcomes for those who received kidneys from donors dying after ligature asphyxiation were similar to controls. Although caution is required in interpreting these findings because of potential selection bias, kidneys from donors dying of ligature asphyxiation suffer an additional warm ischemic insult that does not apparently adversely influence transplant outcomes, even for kidneys from DCD donors.


Reversible logic circuits made of DNA.
We report reversible logic circuits made of DNA. The circuits are based on an AND gate that is designed to be thermodynamically and kinetically reversible and to respond nonlinearly to the concentrations of its input molecules. The circuits continuously recompute their outputs, allowing them to respond to changing inputs. They are robust to imperfections in their inputs.


Performance of astronomical beam combiner prototypes fabricated by hybrid sol-gel technology.
Integrated optics coaxial two, three and four telescope beam combiners have been fabricated by hybrid sol-gel technology for astronomical applications. Temporal and spectral analyses of the output interferometric signal have been performed, and their results are in mutual good agreement. The results of the characterization method employed are cross-checked using contrast measurements obtained independently, demonstrating that the chromatic differential dispersion is the main contributer to contrast reduction. The mean visibility of the fabricated devices is always higher than 95 %, obtained using a source with spectral bandwidth of 50 nm. These results show the capability of hybrid sol-gel technology for fast prototyping of complex chip designs used in astronomical applications.


Low-dose, simple, and fast grating-based X-ray phase-contrast imaging.
Phase sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging and therefore new and otherwise inaccessible information. The use of gratings as optical elements in hard X-ray phase imaging overcomes some of the problems that have impaired the wider use of phase contrast in X-ray radiography and tomography. So far, to separate the phase information from other contributions detected with a grating interferometer, a phase-stepping approach has been considered, which implies the acquisition of multiple radiographic projections. Here we present an innovative, highly sensitive X-ray tomographic phase-contrast imaging approach based on grating interferometry, which extracts the phase-contrast signal without the need of phase stepping. Compared to the existing phase-stepping approach, the main advantages of this new method dubbed "reverse projection" are not only the significantly reduced delivered dose, without the degradation of the image quality, but also the much higher efficiency. The new technique sets the prerequisites for future fast and low-dose phase-contrast imaging methods, fundamental for imaging biological specimens and in vivo studies.