Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial.
Long-term randomized comparisons of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in left main coronary (LM) disease and/or three-vessel disease (3VD) patients have been limited. This analysis compares 3-year outcomes in LM and/or 3VD patients treated with CABG or PCI with TAXUS Express stents. SYNTAX is an 85-centre randomized clinical trial (n= 1800). Prospectively screened, consecutive LM and/or 3VD patients were randomized if amenable to equivalent revascularization using either technique; if not, they were entered into a registry. Patients in the randomized cohort will continue to be followed for 5 years. At 3 years, major adverse cardiac and cerebrovascular events [MACCE: death, stroke, myocardial infarction (MI), and repeat revascularization; CABG 20.2% vs. PCI 28.0%, P< 0.001], repeat revascularization (10.7 vs. 19.7%, P< 0.001), and MI (3.6 vs. 7.1%, P= 0.002) were elevated in the PCI arm. Rates of the composite safety endpoint (death/stroke/MI 12.0 vs. 14.1%, P= 0.21) and stroke alone (3.4 vs. 2.0%, P= 0.07) were not significantly different between treatment groups. Major adverse cardiac and cerebrovascular event rates were not significantly different between arms in the LM subgroup (22.3 vs. 26.8%, P= 0.20) but were higher with PCI in the 3VD subgroup (18.8 vs. 28.8%, P< 0.001). At 3 years, MACCE was significantly higher in PCI- compared with CABG-treated patients. In patients with less complex disease (low SYNTAX scores for 3VD or low/intermediate terciles for LM patients), PCI is an acceptable revascularization, although longer follow-up is needed to evaluate these two revascularization strategies.


The free serratus anterior artery perforator flap-A case report and anatomic study.
We report a reconstructive case using a free serratus anterior artery perforator flap and an anatomic study. A 50-year-old man with upper esophageal sphincter stricture underwent segmental cervical esophageal resection. The size of the defect was approximately 5.5 cm. We then performed esophageal reconstruction using the free serratus anterior artery perforator flap. Esophagography performed on postoperative day 7 revealed no definite leakage and a viable anastomosis site with wide patency. No complications developed during the long-term follow-up period of 3 years. We reviewed the literature and performed an anatomic study using four fresh cadavers. We performed an angiographic study using two specimens and dissection of this perforator using other two specimens. We found that a direct connection existed between the serratus anterior artery and intercostal perforator to the skin in two of eight chests. The connection was located at the 4th intercostal space in the left chest of one cadaver and at the 6th/7th intercostal space in the left chest of the other cadaver. The free serratus anterior artery perforator flap is a new flap that could be considered for use during the elevation of a perforator flap in the lateral chest area, and especially in the area overlying the serratus anterior muscle. © 2016 Wiley Periodicals, Inc. Microsurgery 36:339-344, 2016.


The bacterial curli system possesses a potent and selective inhibitor of amyloid formation.
Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic protein CsgC was a highly effective inhibitor of CsgA amyloid formation. In the absence of CsgC, CsgA formed toxic intracellular aggregates. In vitro, CsgC inhibited CsgA amyloid formation at substoichiometric concentrations and maintained CsgA in a non-β-sheet-rich conformation. Interestingly, CsgC inhibited amyloid assembly of human α-synuclein, but not Aβ42, in vitro. We identified a common D-Q-Φ-X0,1-G-K-N-ζ-E motif in CsgC client proteins that is not found in Aβ42. CsgC is therefore both an efficient and selective amyloid inhibitor. Dedicated functional amyloid inhibitors may be a key feature that distinguishes functional amyloids from disease-associated amyloids.


Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa.
In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection. We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization. A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27). Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499 [controlled-trials.com].).


Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo.
Tumour carbonic anhydrase IX (CAIX), a hypoxia-inducible tumour-associated cell surface enzyme, is thought to acidify the tumour microenvironment by hydrating CO2 to form protons and bicarbonate, but there is no definitive evidence for this in solid tumours in vivo. We used 1H magnetic resonance spectroscopic imaging (MRSI) of the extracellular pH probe imidazolyl succinic acid (ISUCA) to measure and spatially map extracellular pH in HCT116 tumours transfected to express CAIX and empty vector controls in SCID mice. We also measured intracellular pH in situ with 31P MRS and measured lactate in freeze-clamped tumours. CAIX-expressing tumours had 0.15 pH-unit lower median extracellular pH than control tumours (pH 6.71 tumour vs pH 6.86 control, P = 0.01). Importantly, CAIX expression imposed an upper limit for tumour extracellular pH at 6.93. Despite the increased lactate concentration in CAIX-expressing tumours, 31P MRS showed no difference in intracellular pH, suggesting that CAIX acidifies only the tumour extracellular space. CAIX acidifies the tumour microenvironment, and also provides an extracellular pH control mechanism. We propose that CAIX thus acts as an extracellular pH-stat, maintaining an acidic tumour extracellular pH that is tolerated by cancer cells and favours invasion and metastasis.


What happens to defaulters from a diabetic clinic?
The annual rate at which patients defaulted from follow up at the Wolverhampton diabetic clinic between 1971 and 1981 was 4.1% overall and 3.5% in white patients. In 1982 a study was started to discover what happened to white patients, born after 1919, who defaulted from the hospital clinic. There were 162 defaulters, of whom 19 had died. Of the remaining 143 patients, 19 were attending another hospital diabetic clinic, 22 had moved out of the area, and 28 refused to participate in the study. Seventy four agreed to participate: 39 were treated with diet, 15 with oral hypoglycaemic agents, and 20 with insulin. They were matched for sex, age, treatment, and duration of diabetes with patients attending the clinic. Non-insulin dependent defaulters were significantly more overweight at diagnosis (40% v 25%; p less than 0.05) and remained more obese. They developed significantly higher diastolic blood pressure (94 v 86 mm Hg; p less than 0.02) and higher haemoglobin A1 (HbA1) concentrations (11.7% v 8.4%; p less than 0.01). They had significantly more neuropathy at reassessment (15 v 6 out of 54; p less than 0.05) and a greater incidence of new retinopathy (p less than 0.02), which correlated with their higher diastolic blood pressures (p less than 0.01) and HbA1 concentration (p less than 0.02). In defaulters who were treated with insulin only the prevalence of neuropathy was significantly different from that in controls (p less than 0.05). Defaulters received minimal medical supervision and suffered greater morbidity than regular attenders at the clinic.


Risk factors for neck pain: a longitudinal study in the general population.
The objective of the study was to examine the 1-year cumulative incidence of episodic neck pain and to explore its associations with individual risk factors, including a history of previous neck injury. A baseline cross-sectional survey of an adult general population sample made up of all 7669 adults aged 18-75 years, registered with two family practices in South Manchester, United Kingdom, identified the study population of adults with no current neck pain. This study population was surveyed again 12 months later to identify all those who had experienced neck pain during the follow-up period. At follow-up, cumulative 1-year episode incidence of neck pain was estimated at 17.9% (95% confidence interval 16.0-19.7%). Incidence was independent of age, but was more common in women. A history of previous neck injury at baseline was a significant risk factor for subsequent neck pain in the follow-up year (risk ratio 1.7, 95% confidence interval 1.2-2.5), independent of gender and psychological status. Other independent baseline risk factors for subsequent neck pain included number of children, poor self-assessed health, poor psychological status and a past history of low back pain. We have carried out a prospective study in a general population sample and demonstrated that established risk factors for chronic pain predict future episodes of neck pain, and shown that in addition a history of neck injury is an independent and distinct risk factor. This finding may have major public health and medicolegal implications.


Hospital exposure in a UK population, and its association with bacteraemia.
Despite the importance of healthcare-associated infection, few studies have quantified the association between severe infection and hospital exposure in UK populations. Our aim was to estimate the proportion of the population with recent hospital admission, together with rates of infection in hospital-exposed and hospital-naïve populations. We studied bacteraemia as a marker of severe infection in a population of 550,000, served by two hospitals, between 1 April 2000 and 31 March 2005. Hospital-exposed persons accounted for 8.3% of the population, defined as having been resident in a hospital in the last year. The hospital-exposed population accounted for 55% of all admissions, and 42% of emergency admissions to medical, paediatric or surgery departments. After adjustment for age, the hospital-exposed group had much higher rates of admission bacteraemia. Age-standardised incidence rate ratios relative to hospital-naïve patients were 43 [95% confidence interval (CI): 22-85] for meticillin-resistant Staphylococcus aureus (MRSA), 20 (15-27) for S. aureus other than MRSA, 7.3 (5.2-10) for Streptococcus pneumoniae, and 14 (11-18) for E. coli. MRSA was common among hospital-exposed admissions, including emergencies in hospital-exposed men, rates of admission MRSA bacteraemia (31 per 100,000 per annum) and S. pneumoniae bacteraemia (33 per 100,000 per annum) were similar. This quantitative analysis confirms that prior hospital admission is a major risk factor for bacteraemia on hospital admission; it is unclear whether acquisition of pathogens in hospital, co-morbidity or other factors explain this.


Reduced C-afferent fibre density affects perceived pleasantness and empathy for touch.
We examined patients with a heritable disorder associated with a mutation affecting the nerve growth factor beta gene. Their condition has been classified as hereditary sensory and autonomic neuropathy type V. Carriers of the mutation show a reduction in density of thin and unmyelinated nerve fibres, including C afferents. A distinct type of unmyelinated, low-threshold mechanoreceptive C fibre, the C-tactile afferent, is present in hairy but not glabrous skin of humans and other mammals. They have been implicated in the coding of pleasant, hedonic touch of the kind that occurs in affiliative social interactions. We addressed the relationship between C fibre function and pleasant touch perception in 10 individuals from a unique population of mutation carriers in Sweden. We also investigated the effect of reduced C-fibre density on patients' evaluation of observed interpersonal touch (empathy). Results showed that patients perceived gentle, slow arm stroking, optimal for eliciting C-tactile afferent responses (1-10 cm/s), as less pleasant than did matched controls and also differed in their rating patterns across stimulation velocities. Further, patients' blood-oxygen-level-dependent responses in posterior insular cortex--a target for C afferents--were not modulated by stimulation optimal for activating C-tactile afferents. Hence, perception of the hedonic aspect of dynamic touch likely depends on C-tactile afferent density. Closely similar patterns between individuals' ratings of felt and seen touch suggest that appraisal of others' touch is anchored in one's own perceptual experience, whether typical or atypical.


Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder: A Population-Based Birth Cohort, Sibling Control Study.
Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding. To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses. This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016. Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference. Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register. Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events. A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.


Families of patients with polytrauma: Understanding the evidence and charting a new research agenda.
Although research shows that caring for a family member with chronic disease or disability can cause significant distress for caregivers, it also shows that families that function well and adequately support patients can improve the quality of life and health outcomes for their ill or disabled family member. Currently, little knowledge exists about how families function and cope after a loved one has sustained polytrauma, the multiple traumatic injuries that often include traumatic brain injury (TBI). We summarize the polytrauma and TBI research about family needs during rehabilitation and recovery, describe current efforts to improve family-centered care, and detail approaches for understanding family resilience and the long-term consequences of injuries on families. We conclude with recommendations for future research in inpatient and outpatient settings where evidence has been limited for families of patients with TBI and is nonexistent for families of patients with polytrauma. Understanding many of these issues will help to better inform families of policies for benefits and resources and help researchers and clinicians plan for appropriate interventions.


Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer.
No previous study has addressed the efficacy of NF-κB blockade when bladder tumors develop acquired resistance toward CDDP-treatments. We investigated the changes in NF-κB activation and therapeutic impact of NF-κB blockade by the novel NF-κB inhibitor dehydroxymethyl derivative of epoxyquinomicin (DHMEQ) in CDDP-resistant bladder cancer cells. Two human invasive bladder cancer cell lines, T24 and T24PR, were used. The T24PR cell line was newly established as an acquired platinum-resistant subline by culturing in CDDP-containing medium for 6 months. Expression of intranuclear p65 protein in the fractionated two cell lines was determined by Western blotting analysis. DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay. The cytotoxic effects and induction of apoptosis were analyzed in vivo and in vitro. Intranuclear expression and DNA-binding activity of p65 were strongly enhanced in T24PR cells compared with those of T24 cells, and both were significantly suppressed by DHMEQ. Lowered cell viability and strong induction of apoptosis were observed by treatment with DHMEQ alone in these chemo-resistant cells compared with parent cells. As T24PR cells did not show dramatic cross-resistance to paclitaxel in the in vitro study, we next examined whether the combination of DHMEQ with paclitaxel could enhance the therapeutic effect of the paclitaxel treatment in T24PR tumors. Using mouse xenograft models, the mean volume of tumors treated with the combination of DHMEQ (2 mg/kg) and paclitaxel (10 mg/kg) was significantly smaller than those treated with paclitaxel alone (p < 0.05), and the reduction of tumor volume in mice treated with DHMEQ in combination with paclitaxel and paclitaxel alone as compared to vehicle control was 66.9% and 17.0%, respectively. There was a distinct change in the activation level of NF-κB between T24 and T24PR cells, suggesting strong nuclear localization of NF-κB could be a promising target after developing acquired platinum-resistance in bladder cancer.


Molecular phylogeny, evolutionary rates, and divergence timing of the symbiotic dinoflagellate genus Symbiodinium.
Symbiotic dinoflagellates belonging to the genus Symbiodinium are found in association with a wide variety of shallow-water invertebrates and protists dwelling in tropical and subtropical coral-reef ecosystems. Molecular phylogeny of Symbiodinium, initially inferred using nuclear ribosomal genes, was recently confirmed by studies of chloroplastic and mitochondrial genes, but with limited taxon sampling and low resolution. Here, we present the first complete view of Symbiodinium phylogeny based on concatenated partial sequences of chloroplast 23S-rDNA (cp23S) and nuclear 28S-rDNA (nr28S) genes, including all known Symbiodinium lineages. Our data produced a well resolved phylogenetic tree and provide a strong statistical support for the eight distinctive clades (A-H) that form the major taxa of Symbiodinium. The relative-rate tests did not show particularly high differences between lineages and both analysed markers. However, maximum likelihood ratio tests rejected a global molecular clock. Therefore, we applied a relaxed molecular clock method to infer the divergence times of all extant lineages of Symbiodinium, calibrating its phylogenetic tree with the fossil record of soritid foraminifera. Our analysis suggests that Symbiodinium originated in early Eocene, and that the majority of extant lineages diversified since mid-Miocene, about 15 million years ago.


Cholesterol synthesis pathway genes in prostate cancer are transcriptionally downregulated when tissue confounding is minimized.
The relationship between cholesterol and prostate cancer has been extensively studied for decades, where high levels of cellular cholesterol are generally associated with cancer progression and less favorable outcomes. However, the role of in vivo cellular cholesterol synthesis in this process is unclear, and data on the transcriptional activity of cholesterol synthesis pathway genes in tissue from prostate cancer patients are inconsistent. A common problem with cancer tissue data from patient cohorts is the presence of heterogeneous tissue which confounds molecular analysis of the samples. In this study we present a general method to minimize systematic confounding from stroma tissue in any prostate cancer cohort comparing prostate cancer and normal samples. In particular we use samples assessed by histopathology to identify genes enriched and depleted in prostate stroma. These genes are then used to assess stroma content in tissue samples from other prostate cancer cohorts where no histopathology is available. Differential expression analysis is performed by comparing cancer and normal samples where the average stroma content has been balanced between the sample groups. In total we analyzed seven patient cohorts with prostate cancer consisting of 1713 prostate cancer and 230 normal tissue samples. When stroma confounding was minimized, differential gene expression analysis over all cohorts showed robust and consistent downregulation of nearly all genes in the cholesterol synthesis pathway. Additional Gene Ontology analysis also identified cholesterol synthesis as the most significantly altered metabolic pathway in prostate cancer at the transcriptional level. The surprising observation that cholesterol synthesis genes are downregulated in prostate cancer is important for our understanding of how prostate cancer cells regulate cholesterol levels in vivo. Moreover, we show that tissue heterogeneity explains the lack of consistency in previous expression analysis of cholesterol synthesis genes in prostate cancer.


Characteristics of chiropractic patients treated at the University of Johannesburg chiropractic student clinic and relevance to the educational process.
This study aimed to analyze the demographic and descriptive information of new patients presenting to an educational institution-based chiropractic student clinic in South Africa that could then be used to draw comparisons to other international chiropractic student clinics and local practices. We conducted a retrospective descriptive study of all new patient files from January 1, 2016, to July 31, 2016. The variables extracted were age, health profiles, number of musculoskeletal complaints, treatment protocol, and number of treatments that patients received for the initial complaint. Data were analyzed using cross-tabulations and multidimensional χ2 tests. There were 865 files reviewed. Most patients were aged between 20 and 24 years. Lumbar and pelvic complaints were most common (42.2%), followed by the cervical spine (28%). Lumbar (18.8%) and cervical (16.8%) biomechanical conditions, followed by lumbar myofascial pain syndrome (7.6%), were the most common problems. Musculoskeletal conditions were reported in 99% of cases. The majority (80%) of patients received 9 or fewer treatments for their initial complaint. Manipulation was used in 93.9% of cases, followed by mobilization (8.8%), interferential current (23.5%), and dry needling (19.1%). Data gathered suggest that there are some general similarities with international training institutions. There are also differences between the study sample and international institutions and South African private chiropractic practice. The dissimilarities were a younger patient population, a lower number of treatment visits, and low exposure to nonmusculoskeletal conditions. These differences may affect the breadth of student education and require further investigation.


A Histopathology-based Assessment of Biological Behavior in Oral Hyalinizing Extraosseous Lesions by Differential Stains.
The assessment of hyalinization to determine aggressive behavior in oral pathological lesions is a scarcely researched field that requires further exploration. The current study aims to predict the biological behavior of oral hyalinizing extraosseous lesions (OHEOL) by employing four differential stains with clinicopathologic correlation. The study was performed on retrospectively diagnosed formalin-fixed paraffin-embedded cases of salivary gland tumors (SGTs) (n = 13), benign soft tissue (BST) lesions (n = 24), and oral submucous fibrosis (OSMF) (n = 53). The hematoxylin and eosin-stained sections were analyzed for the severity of hyalinization (SOH). Differential stains periodic acid Schiff (PAS), Alcian blue, safranin O, and picrosirius red with polarizing microscopy were used to assess the components of hyalinized tissue. The SOH was correlated with differential staining characteristics and clinicopathologic features to analyze possible correlation with aggressive potential in BST, advancement of disease in OSMF, and recurrence in SGT. Intensity of picrosirius red stain significantly correlated with SOH of SGTs (p = 0.044). The intensity of PAS stain (p = 0.040), picrosirius red polarizing greenish-yellow color (p = 0.002), and pattern of distribution of picrosirius red (p = 0.023) significantly correlated with recurrence of SGTs. The intensity of differential stains increased with the SOH in BST lesions indicating their correlation with SOH. The intensity (p = 0.008) and pattern (p = 0.010) of Alcian blue staining and intensity of safranin O stain (p = 0.003) significantly correlated with SOH in OSMF. Picrosirius red polarizing color reddish and yellowish red (p = 0.002) significantly correlated with SOH distinguishing early and advanced OSMF. Picrosirius red and PAS stains are reliable indicators of SOH and recurrence potential in SGT. Alcian blue, safranin O, and picrosirius red polarizing colors enable detection of SOH and accurately distinguish early from advanced OSMF. SOH can be considered as a histological predictor of aggressive biologic behavior in OHEOL. These findings will result in appropriate management protocols.


The economic cost of posterior capsule tear at cataract surgery.
To estimate the direct financial burden to healthcare purchasers of a posterior capsule tear (PCT) during cataract surgery. A retrospective data analysis of cataract surgeries was performed. Patients who had surgery in the 2-year period from April 2005, with a maximum follow-up, to April 2009 were identified. Patients previously under review for ocular comorbidity apart from cataract were excluded. Each case with PCT was matched with an uncomplicated cataract operation performed on the same list by the same grade of surgeon. For both groups, we extracted details of all additional subsequent visits and interventions. Data on the cost of visits and procedures were provided by the Department of Health. We then compared this data between groups. A total of 100 patients with PCT were matched with 100 controls. The preoperative parameters of the two groups were similar. The cases required a median of 3 (mean 3.6, range 0-24) additional postoperative visits compared with 0 (mean 0.19, range 0-8) for controls, with a median duration of follow-up of 74 (mean 129.5, range 6-1316) days for cases compared to 21 (mean 26.1, range 0-308) days for controls (p=0.000). The average cost of extra visits was £ 475.0 (SD £ 697.8) for cases and £ 69.2 (SD £ 51.0) for controls (p<0.001). Based on the National Health Service national tariff, a PCT during cataract surgery results in significant additional financial cost to healthcare purchasers. A full cost analysis would be required to estimate the additional cost of a PCT for the healthcare provider.


Andrographolide inhibits nuclear factor-κB activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-α-stimulated vascular smooth muscle cells.
Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.


Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis.
The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts. The transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR. IL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10. The findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.


Incidence of complications associated with spinal endoscopic surgery: nationwide survey in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification of Japanese Orthopaedic Association.
This report was conducted to elucidate the current status of spinal endoscopic surgery and relevant incidents through analysis of the results of a questionnaire survey conducted in 2007 by the Committee on Spinal Endoscopic Surgical Skill Qualification of the Japanese Orthopaedic Association (JOA). Questionnaire forms were sent to 2011 training facilities nationwide certified by the JOA, and 1082 of these facilities returned the filled questionnaires (response rate 53.8%). Of these facilities, 257 (23.8% of the responding facilities) undertook spinal endoscopic surgery in 2007. These institutions were asked to fill in the survey form with the details of the operations and relevant incidents as well as the incident levels. In total, the 257 facilities performed 6239 spinal endoscopic surgeries during 2007. Posterior spinal endoscopic surgery constituted most of the operations (6217 cases, 98.2%) including 4336 cases of microendoscopic discectomy (MED), 1273 cases of microendoscopic laminectomy or fenestration, and 379 cases of transforaminal or posterior lumbar interbody fusion. The total number of incidents was 133 (2.13%). The numbers of incidents by operative method were 75 (56.4%) during MED, 57 (42.9%) during microendoscopic laminectomy or fenestration, and 1 (0.8%) during interbody fusion. Of 133 incidents, dural tear occurred in 99 (74.4%), injury of the cauda equina or a nerve root in 7 (5.3%), facet fracture in 7 (5.3%), hematoma and wrong level in 6 each (4.5%), and wrong side and bedsore in 1 each (0.8%). The incident level was level 1 in 6, level 2 in 24, level 3a in 82, level 3b in 16, level 4 in 5, and level 5 (fatal) in 0. The results of this survey revealed an increasing trend of spinal endoscopic surgery and a decreasing trend of the complication rates. The complication rates of spinal endoscopic surgery were not higher than those of conventional surgery, indicating the safety of this surgical method.


Molecular Mechanisms of Phenylpropane-Synthesis-Related Genes Regulating the Shoot Blight Resistance of Bambusa pervariabilis × Dendrocalamopsis grandis.
Bambusa pervariabilis × Dendrocalamopsis grandis shoot blight caused by Arthrinium phaeospermum is a fungal disease that has affected a large area in China in recent years. However, it is not clear which genes are responsible for the disease resistance of B. pervariabilis × D. grandis. Based on the analysis of transcriptome and proteome data, two genes, CCoAOMT2 and CAD5, which may be involved in disease resistance, were screened. Two gene expression-interfering varieties, COF RNAi and CAD RNAi were successfully obtained using RNAi technology. Quantitative real-time fluorescence (qRT-PCR) results showed that CCoAOMT2 gene, CAD5 gene and seven related genes expression was down-regulated in the transformed varieties. After inoculating pathogen spore suspension, the incidence and disease index of cof-RNAi and cad-RNAi transformed plants increased significantly. At the same time, it was found that the content of total lignin and flavonoids in the two transformed varieties were significantly lower than that of the wild-type. The subcellular localization results showed that both CCoAOMT2 and CAD5 were localized in the nucleus and cytoplasm. The above results confirm that the CCoAOMT2 and CAD5 genes are involved in the resistance of B. pervariabilis × D.grandis to shoot blight through regulating the synthesis of lignin and flavonoids.


Folic acid prevents congenital malformations in the offspring of diabetic mice.
It is well known that maternal diabetes causes various congenital malformations. Although there are many reports that folic acid (FA) administration in pregnancy reduces the risk of birth defects including neural tube defects (NTDs), a precise analysis on the preventive effect of FA against diabetic embryopathy has not been done yet. In this study, we analyzed the preventive effects of FA on congenital malformations including NTDs, cardiovascular, and skeletal malformations using a diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were examined for congenital malformations. FA did not affect plasma glucose levels. In the DM control group, the incidence of NTDs, cardiovascular, and skeletal malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of embryos from DM control group on day 9.5, and the apoptosis was decreased by FA treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly lowered in DM control group compared with those in non-DM group, and FA treatment did not show a significant effect. These results indicate that FA is effective for the prevention of various diabetic embryopathy including NTDs, cardiovascular, and skeletal malformations, and suggested that this effect is independent from homocysteine metabolism and possibly mediated by decreasing the abnormal apoptosis during organogenesis.


The signalling factor PI3K is a specific regulator of the clathrin-independent dynamin-dependent endocytosis of IL-2 receptors.
Receptor-mediated endocytosis is an essential process used by eukaryotic cells to internalise many molecules. Several clathrin-independent endocytic routes exist, but the molecular mechanism of each pathway remains to be uncovered. The present study focuses on a clathrin-independent dynamin-dependent pathway used by interleukin 2 receptors (IL-2R), essential players of the immune response. Ras-related C3 botulinum toxin substrate (Rac1) and its targets, the p21-activated kinases (Pak), are specific regulators of this pathway, acting on cortactin and actin polymerization. The present study reveals a dual and specific role of phosphatidylinositol 3-kinase (PI3K) in IL-2R endocytosis. Inhibition of the catalytic activity of PI3K strongly affects IL-2R endocytosis, in contrast to transferrin (Tf) uptake, a marker of the clathrin-mediated pathway. Moreover, Vav2, a GTPase exchange factor (GEF) induced upon PI3K activation, is specifically involved in IL-2R entry. The second action of PI3K is through its regulatory subunit, p85α, which binds to and recruits Rac1 during IL-2R internalisation. Indeed, the overexpression of a p85α mutant missing the Rac1 binding motif leads to the specific inhibition of IL-2R endocytosis. The inhibitory effect of this p85α mutant could be rescued by the overexpression of either Rac1 or the active form of Pak, indicating that p85α acts upstream of the Rac1-Pak cascade. Finally, biochemical and fluorescent microscopy techniques reveal an interaction between p85α, Rac1 and IL-2R that is enhanced by IL-2. In summary, our results indicate a key role of class I PI3K in IL-2R endocytosis that creates a link with IL-2 signalling.


Improving the rates of quitting smoking for veterans with posttraumatic stress disorder.
Smoking is highly prevalent and refractory among people with posttraumatic stress disorder (PTSD). This study aimed to improve the rate of quitting smoking for veterans with PTSD by integrating treatment for nicotine dependence into mental health care. Smokers undergoing treatment for PTSD (N=66) were randomly assigned to 1) tobacco use treatment delivered by mental health providers and integrated with psychiatric care (integrated care) versus 2) cessation treatment delivered separately from PTSD care by smoking-cessation specialists (usual standard of care). Seven-day point prevalence abstinence was the primary outcome, measured at 2, 4, 6, and 9 months after random assignment. Data were analyzed by using a generalized estimating equations approach following the intent-to-treat principle. Subjects assigned to integrated care were five times more likely than subjects undergoing the usual standard of care to abstain from smoking across follow-up assessment intervals (odds ratio=5.23). Subjects in the integrated care condition were significantly more likely than subjects in usual standard of care to receive transdermal nicotine and nicotine gum. They also received a greater number of smoking-cessation counseling sessions. Stopping smoking was not associated with worsening symptoms of PTSD or depression. Smoking-cessation interventions can be safely incorporated into routine mental health care for PTSD and are more effective than treatment delivered separately by a specialized smoking-cessation clinic. Integrating cessation treatment into psychiatric care may have the potential for improving smoking quit rates in other populations of chronically mentally ill smokers.


A Large-Scale Circuit Mechanism for Hierarchical Dynamical Processing in the Primate Cortex.
We developed a large-scale dynamical model of the macaque neocortex, which is based on recently acquired directed- and weighted-connectivity data from tract-tracing experiments, and which incorporates heterogeneity across areas. A hierarchy of timescales naturally emerges from this system: sensory areas show brief, transient responses to input (appropriate for sensory processing), whereas association areas integrate inputs over time and exhibit persistent activity (suitable for decision-making and working memory). The model displays multiple temporal hierarchies, as evidenced by contrasting responses to visual versus somatosensory stimulation. Moreover, slower prefrontal and temporal areas have a disproportionate impact on global brain dynamics. These findings establish a circuit mechanism for "temporal receptive windows" that are progressively enlarged along the cortical hierarchy, suggest an extension of time integration in decision making from local to large circuits, and should prompt a re-evaluation of the analysis of functional connectivity (measured by fMRI or electroencephalography/magnetoencephalography) by taking into account inter-areal heterogeneity.


Health and economic consequences of counterfeit drugs.
"Counterfeit Drugs Kill" is the slogan the World Health Organization (WHO) uses in its anti-counterfeiting campaign. International organizations, governments of developed and developing countries, and the pharmaceutical industry created the IMPACT initiative (International Medical Products Anti-Counterfeiting Taskforce) to take on the thriving illegal industry that makes profits by selling fake drugs. However, before committing resources, policy makers want to assess the burden caused by counterfeit drugs in comparison with other health problems that compete for the limited resources available.


Hinokitiol Negatively Regulates Immune Responses through Cell Cycle Arrest in Concanavalin A-Activated Lymphocytes.
Autoimmune diseases are a group of chronic inflammatory diseases that arise from inappropriate inflammatory responses. Hinokitiol, isolated from the wood of Chamaecyparis taiwanensis, engages in multiple biological activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains incomplete. Thus, we determined the effects of hinokitiol on concanavalin A- (ConA-) stimulated T lymphocytes from the spleens of mice. In the present study, the MTT assay revealed that hinokitiol (1-5 μM) alone did not affect cell viability of lymphocytes, but at the concentration of 5 μM it could reduce ConA-stimulated T lymphocyte proliferation. Moreover, propidium iodide (PI) staining revealed that hinokitiol arrested cell cycle of T lymphocytes at the G0/G1 phase. Hinokitiol also reduced interferon gamma (IFN-γ) secretion from ConA-activated T lymphocytes, as detected by an ELISA assay. In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression. These results revealed that hinokitiol may regulate immune responses. In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-γ secretion in ConA-stimulated T lymphocytes, thereby arresting cell cycle at the G0/G1 phase. In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases.


Precision Modulation of Neurodegenerative Disease-Related Gene Expression in Human iPSC-Derived Neurons.
The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and the subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means to recapitulate molecular phenotypes of neurodegenerative diseases in vitro. However, it remains challenging to conduct precise manipulations of gene expression in iPSC-derived neurons towards modeling complex human neurological diseases. The application of CRISPR/Cas9 to mammalian systems is revolutionizing the utilization of genome editing technologies in the study of molecular contributors to the pathogenesis of numerous diseases. Here, we demonstrate that CRISPRa and CRISPRi can be used to exert precise modulations of endogenous gene expression in fate-committed iPSC-derived neurons. This highlights CRISPRa/i as a major technical advancement in accessible tools for evaluating the specific contributions of critical neurodegenerative disease-related genes to neuropathogenesis.


[Bilateral blockade of the pudend nerve to hemorrhoidectomy in achondroplasic patient: case report.].
The achondroplasic dwarfism or achondroplasia is the most common form of dwarfism and occurs, in most of the cases, as a result of spontaneous genetic alteration. The anesthesia in these patients presents several particularities. The objective of the present report was to describe an achondroplasic patient case, with a previous history of surgical procedure of the vertebral column for medullar decompression, submitted to haemorrhoidectomy through the bilateral blockade of the pudend nerves. Male patient, 47 years old, achondroplasic, hospitalized to perform hemorrhoidectomy. Upon physical examination, he presented a shortened neck with limited extension of the head, Mallampati class IV, thyromental distance of 6 cm and opening of the mouth of 3.5 cm. The vertebral column presented thoracic kyphosis and severe lumbar lordosis, in addition to a surgical scar in the lumbar region. A bilateral blockade of the pudend nerves was performed with ropivacaine at 1%, via transperineal, with isolated needle measuring 0.8 mm x 100 mm 21G (Stimuplex A100 BBraun, Melsungen, Germany) connected to the peripheral nerve stimulator (Stimuplex-DIG, BBraun).The patient was positioned in ventral decubitus and the surgery started after 15 minutes of anesthetic administration. During the entire procedure, the patient remained conscious and did not report pain or discomfort. Up to the moment his hospital discharge (22 hours after the performance of the blockade), the patient did not mention pain, discomfort, nausea, vomit, motor blockade, urinary retention or incontinence. After his discharge from the hospital, he evolved well presenting evacuation after 31 hours from surgery. The case illustrated the use of the bilateral blockade of the pudend nerves, with the help of the neurostimulator, as an isolated anesthetic techniques for hemorrhoidectomy.


Understanding why patients of low socioeconomic status prefer hospitals over ambulatory care.
Patients with low socioeconomic status (SES) use more acute hospital care and less primary care than patients with high socioeconomic status. This low-value pattern of care use is harmful to these patients' health and costly to the health care system. Many current policy initiatives, such as the creation of accountable care organizations, aim to improve both health outcomes and the cost-effectiveness of health services. Achieving those goals requires understanding what drives low-value health care use. We conducted qualitative interviews with forty urban low-SES patients to explore why they prefer to use hospital care. They perceive it as less expensive, more accessible, and of higher quality than ambulatory care. Efforts that focus solely on improving the quality of hospital care to reduce readmissions could, paradoxically, increase hospital use. Two different profile types emerged from our research. Patients in Profile A (five or more acute care episodes in six months) reported social dysfunction and disability. Those in Profile B (fewer than five acute care episodes in six months) reported social stability but found accessing ambulatory care to be difficult. Interventions to improve outcomes and values need to take these differences into account.


Brain-actuated gait trainer with visual and proprioceptive feedback.
Brain-machine interfaces (BMIs) have been proposed in closed-loop applications for neuromodulation and neurorehabilitation. This study describes the impact of different feedback modalities on the performance of an EEG-based BMI that decodes motor imagery (MI) of leg flexion and extension. We executed experiments in a lower-limb gait trainer (the legoPress) where nine able-bodied subjects participated in three consecutive sessions based on a crossover design. A random forest classifier was trained from the offline session and tested online with visual and proprioceptive feedback, respectively. Post-hoc classification was conducted to assess the impact of feedback modalities and learning effect (an improvement over time) on the simulated trial-based performance. Finally, we performed feature analysis to investigate the discriminant power and brain pattern modulations across the subjects. (i) For real-time classification, the average accuracy was [Formula: see text]% and [Formula: see text]% for the two online sessions. The results were significantly higher than chance level, demonstrating the feasibility to distinguish between MI of leg extension and flexion. (ii) For post-hoc classification, the performance with proprioceptive feedback ([Formula: see text]%) was significantly better than with visual feedback ([Formula: see text]%), while there was no significant learning effect. (iii) We reported individual discriminate features and brain patterns associated to each feedback modality, which exhibited differences between the two modalities although no general conclusion can be drawn. The study reported a closed-loop brain-controlled gait trainer, as a proof of concept for neurorehabilitation devices. We reported the feasibility of decoding lower-limb movement in an intuitive and natural way. As far as we know, this is the first online study discussing the role of feedback modalities in lower-limb MI decoding. Our results suggest that proprioceptive feedback has an advantage over visual feedback, which could be used to improve robot-assisted strategies for motor training and functional recovery.


Fluidized muds: a novel setting for the generation of biosphere diversity through geologic time.
Reworked and fluidized fine-grained deposits in energetic settings are a major modern-day feature of river deltas and estuaries. Similar environments were probably settings for microbial evolution on the early Earth. These sedimentary systems act as efficient biogeochemical reactors with high bacterial phylogenetic diversity and functional redundancy. They are temporally rather than spatially structured, with repeated cycling of redox conditions and successive stages of microbial metabolic processes. Intense reworking of the fluidized bed entrains bacteria from varied habitats providing new, diverse genetic materials to contribute to horizontal gene transfer events and the creation of new bacterial ecotypes. These vast mud environments may act as exporters and promoters of biosphere diversity and novel adaptations, potentially on a globally important scale.


High altitude pulmonary edema (HAPE) in a Himalayan trekker: a case report.
High altitude pulmonary edema is a non-cardiogenic form of pulmonary edema that develops in unacclimatized individuals at altitudes over 2500 m. Early recognition of symptoms and immediate descent are important for successful treatment. Despite early signs and symptoms of high altitude illness, many trekkers tend to push themselves to the maximum limit. Some of them, such as the case reported here, choose to ascend on horse-back which is extremely dangerous and can be fatal. A 55 years of age Indian ethnic South African lady was emergency air-lifted from 4410 m altitude in the Nepal Himalayas to Kathamandu (1300 m) with a suspected case of high altitude pulmonary edema. She had continued ascending despite experiencing mild altitude symptoms at Namche (3440 m), and these symptoms worsened considerably at Tengboche (3860 m). At the very start of her trek, just after Lukla (2800 m), she suffered from sore throat, and had consequently begun a course of antibiotics (azithromycin) for a suspected throat infection. She had planned to continue ascending on horse back to complete the trek, however her condition deteriorated further and she had to be medically evacuated.On admission to the clinic her axillary temperature was 99.4 F, blood pressure 120/60 mmHg, pulse rate 72/min, respiratory rate of 25 breaths/min, and pulse oximeter showed saturation of 90% on room air at rest. Right sided crackles on the axillary and posterior region were heard on chest auscultation. Heel to toe test showed no signs of ataxia. The chest radiograph showed patchy infiltrates on the right side. An echocardiogram was done which revealed a high pulmonary artery pressure of 50 mm of Hg. She was diagnosed as resolving high altitude pulmornay edema. She was treated with bed rest, supplemental oxygen and sustained release nifedipine 20 mg (orally) twice a day. On the third day her crackles had cleared significantly and repeat chest radiograph as shown showed remarkable improvement. She felt much better. A repeat echocardiogram revealed a normal pulmonary artery pressure. The case report highlights numerous points:1) Many high altitude trekkers have invested significant time, money and physical efforts in in their ventures and are determined to ascend despite early warning and illnesses. 2) Despite no history of altitude illnesses in previous altitude exposure,inter-current illness (in this case a nonspecific respiratory tract infection) may contribute to the development of high altitude pulmonary edema. 3) Continuing ascent using other transport means, whilst suffering from symptoms of high altitude illness, worsens the condition and could be life threatening. 4) Acetazolamide does not prevent high altitude pulmonary edema-perhaps more so in the cases that have inter-current illness. 5) Descent is the golden rule in all altitude illnesses. Actually 'descent' is advised in any undiagnosed illness at high altitude among sojourners. 6) Finally, an experienced guide who has mountain medicine training is essential. They can be crucial in noticing early signs and symptoms of altitude illnesses to inform the client's safety as in this case.


The six most essential questions in psychiatric diagnosis: a pluralogue part 2: Issues of conservatism and pragmatism in psychiatric diagnosis.
In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM--whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.


Broadband terahertz conductivity and optical transmission of indium-tin-oxide (ITO) nanomaterials.
Indium-tin-oxide (ITO) nanorods (NRs) and nanowhiskers (NWhs) were fabricated by an electron-beam glancing-angle deposition (GLAD) system. These nanomaterials are of interests as transparent conducting electrodes in various devices. Two terahertz (THz) time-domain spectrometers (TDS) with combined spectral coverage from 0.15 to 9.00 THz were used. These allow accurate determination of the optical and electrical properties of such ITO nanomaterials in the frequency range from 0.20 to 4.00 THz. Together with Fourier transform infrared spectroscopic (FTIR) measurements, we found that the THz and far-infrared transmittance of these nanomaterials can be as high as 70% up to 15 THz, as opposed to about 9% for sputtered ITO thin films. The complex conductivities of ITO NRs, NWhs as well films are well fitted by the Drude-Smith model. Taking into account that the volume filling factors of both type of nanomaterials are nearly same, mobilities, and DC conductivities of ITO NWhs are higher than those of NRs due to less severe carrier localization effects in the former. On the other hand, mobilities of sputtered ITO thin films are poorer than ITO nanomaterials because of larger concentration of dopant ions in films, which causes stronger carrier scattering. We note further that consideration of the extreme values of Re{σ} and Im{σ} as well the inflection points, which are functions of the carrier scattering time (τ) and the expectation value of cosine of the scattering angle (γ), provide additional criteria for accessing the accuracy of the extraction of electrical parameters of non-Drude-like materials using THz-TDS. Our studies so far indicate ITO NWhs with heights of ~1000 nm show outstanding transmittance and good electrical characteristics for applications such as transparent conducting electrodes of THz Devices.


Minimal benefit to subsequent intraoperative parathyroid hormone testing after all four glands have been identified.
Modern tools, such as intraoperative parathyroid hormone (IoPTH) assay, reduce operative time and extent of parathyroidectomy. However, the utility of a subsequent final set of IoPTH after all four glands are visualized remains questionable. This study was designed to determine the added value of IoPTH assay following parathyroidectomy with four-gland visualization in patients with primary hyperparathyroidism (PHPT). A retrospective review of patients who underwent parathyroidectomy for PHPT between July 2001 and February 2012 by two experienced endocrine surgeons was performed. Included were patients with operative reports indicating that all four parathyroid glands were identified. Following four-gland visualization a subsequent final set of IoPTH was measured to confirm cure. Cure was defined as at least 50 % fall by 5, 10, or 15 min postexcision compared with preincision levels. Of 1,838 patients that underwent parathyroidectomy, four glands were visualized in 238 cases (13 %). Of those patients meeting inclusion criteria with four glands visualized, the final set of IoPTH fell to cure criteria in 235 patients (98 %). An inadequate drop was documented in three (2 %) patients all of which were found to have multigland disease. Only in one patient (0.4 %) was a fifth parathyroid gland identified and resected. In all three cases, the subsequent final IoPTH did not affect the ultimate outcome or cure rate. When experienced surgeons visualize all four parathyroid glands, drawing a subsequent final set of IoPTH rarely changes the operative course and therefore serves a limited role.


Mhc class II DNA polymorphisms within and between chromosomal species of the Spalax ehrenbergi superspecies in Israel.
Restriction fragment length polymorphisms (RFLPs) of two major histocompatibility class II genes (P alpha 1 and Q beta) were studied in 13 populations of four chromosomal species (2n = 52, 54, 58 and 60) of the mole rat, Spalax ehrenbergi superspecies in Israel. A substantial frequency of allelic fragments was found in both genes for all populations, including a desert isolate. In the P alpha 1 gene, one allelic fragment is a result of a deletion mutation which is diagnostic of the 2n = 52 chromosomal species. All other ten allelic variants are the result of point mutations. All mutations are located in a short region flanking the 3' end of the gene. Based on Mhc polymorphisms we confirm earlier evidence that gene flow does not occur between the older chromosomal species (2n = 52, 54, 58), and that reproductive isolation decreases, progressively from the oldest to the youngest species (2n = 60).


Deep neural networks rival the representation of primate IT cortex for core visual object recognition.
The primate visual system achieves remarkable visual object recognition performance even in brief presentations, and under changes to object exemplar, geometric transformations, and background variation (a.k.a. core visual object recognition). This remarkable performance is mediated by the representation formed in inferior temporal (IT) cortex. In parallel, recent advances in machine learning have led to ever higher performing models of object recognition using artificial deep neural networks (DNNs). It remains unclear, however, whether the representational performance of DNNs rivals that of the brain. To accurately produce such a comparison, a major difficulty has been a unifying metric that accounts for experimental limitations, such as the amount of noise, the number of neural recording sites, and the number of trials, and computational limitations, such as the complexity of the decoding classifier and the number of classifier training examples. In this work, we perform a direct comparison that corrects for these experimental limitations and computational considerations. As part of our methodology, we propose an extension of "kernel analysis" that measures the generalization accuracy as a function of representational complexity. Our evaluations show that, unlike previous bio-inspired models, the latest DNNs rival the representational performance of IT cortex on this visual object recognition task. Furthermore, we show that models that perform well on measures of representational performance also perform well on measures of representational similarity to IT, and on measures of predicting individual IT multi-unit responses. Whether these DNNs rely on computational mechanisms similar to the primate visual system is yet to be determined, but, unlike all previous bio-inspired models, that possibility cannot be ruled out merely on representational performance grounds.


Co-ordinated multidisciplinary approaches for inpatient rehabilitation of older patients with proximal femoral fractures.
Hip fracture is a major cause of morbidity and mortality in older people and its impact, both on the individual and to society, is substantial. To examine the effects of co-ordinated multidisciplinary inpatient rehabilitation, compared with usual (orthopaedic) care, for older patients with hip fracture. We searched the Cochrane Musculoskeletal Injuries Group specialised register (March 2001), MEDLINE (1966 to February 2001), PREMEDLINE (March 28th 2001), and reference lists of articles and books. We also contacted colleagues and trialists. Randomised and quasi-randomised trials of post-surgical care using specialised rehabilitation of mainly older patients (aged 65 years or over) with hip fracture. Trial assignment to included, excluded and awaiting assessment categories, was by consensus. Two reviewers independently assessed trial quality and extracted data. Limited additional information was sought from most trialists. As well as pooling data from primary outcomes, supplementary analyses were performed to combine clinically relevant outcomes and investigate possible explanatory factors. In this substantive update, one new trial has been included. The nine included trials involved 1869 patients. The combined outcomes of death or requiring institutional care showed no significant difference between intervention and control groups (relative risk 0.92; 95% confidence interval 0.82 to 1.04). There was considerable heterogeneity in length of stay and cost data. Using death and deterioration in function as a further combined outcome variable yielded a relative risk of 0.92 (95% confidence interval 0.82 to 1.02). This should be interpreted with caution due to heterogeneity. No quality of life measures were reported and the two trials investigating carer burden showed no detrimental effect from the intervention. The review update did not result in any new data for these outcomes. The available trials reviewed had different aims, interventions and outcomes. Combined outcome measures (e.g. death or institutional care) tended to be better for patients receiving co-ordinated inpatient rehabilitation, but the results were heterogeneous and not statistically significant. Future trials of post-surgical care involving inpatient rehabilitation, or other models such as 'early supported discharge' and 'hospital at home' schemes, should aim to establish both effectiveness and cost effectiveness of multidisciplinary rehabilitation overall, rather than attempt to evaluate its components.


Presence and incidence of food-borne pathogens in Australian chicken litter.
1. Litter samples were collected at the end of the production cycle from spread litter in a single shed from each of 28 farms distributed across the three Eastern seaboard States of Australia. 2. The geometric mean for Salmonella was 44 Most Probable Number (MPN)/g for the 20 positive samples. Five samples were between 100 and 1000 MPN/g and one at 10(5) MPN/g, indicating a range of factors are contributing to these varying loads of this organism in litter. 3. The geometric mean for Campylobacter was 30 MPN/g for the 10 positive samples, with 7 of these samples being <100 MPN/g. The low prevalence and incidence of Campylobacter were possibly due to the rapid die-off of this organism. 4. E. coli values were markedly higher than the two key pathogens (geometric mean 20 x 10(5) colony forming units (cfu)/g) with overall values being more or less within the same range across all samples in the trial, suggesting a uniform contribution pattern of these organisms in litter. 5. Listeria monocytogenes was absent in all samples and this organism appears not to be an issue in litter. 6. The dominant (70% of the isolates) Salmonella serovar was S. Sofia (a common serovar isolated from chickens in Australia) and was isolated across all regions. Other major serovars were S. Virchow and S. Chester (at 10%) and S. Bovismorbificans and S. Infantis (at 8%) with these serovars demonstrating a spatial distribution across the major regions tested. 7. There is potential to re-use litter in the environment depending on end use and the support of relevant application practices and guidelines.


Optimal Loading for Maximizing Power During Sled-Resisted Sprinting.
To ascertain whether force-velocity-power relationships could be compiled from a battery of sled-resisted overground sprints and to clarify and compare the optimal loading conditions for maximizing power production for different athlete cohorts. Recreational mixed-sport athletes (n = 12) and sprinters (n = 15) performed multiple trials of maximal sprints unloaded and towing a selection of sled masses (20-120% body mass [BM]). Velocity data were collected by sports radar, and kinetics at peak velocity were quantified using friction coefficients and aerodynamic drag. Individual force-velocity and power-velocity relationships were generated using linear and quadratic relationships, respectively. Mechanical and optimal loading variables were subsequently calculated and test-retest reliability assessed. Individual force-velocity and power-velocity relationships were accurately fitted with regression models (R2 > .977, P < .001) and were reliable (ES = 0.05-0.50, ICC = .73-.97, CV = 1.0-5.4%). The normal loading that maximized peak power was 78% ± 6% and 82% ± 8% of BM, representing a resistance of 3.37 and 3.62 N/kg at 4.19 ± 0.19 and 4.90 ± 0.18 m/s (recreational athletes and sprinters, respectively). Optimal force and normal load did not clearly differentiate between cohorts, although sprinters developed greater maximal power (17.2-26.5%, ES = 0.97-2.13, P < .02) at much greater velocities (16.9%, ES = 3.73, P < .001). Mechanical relationships can be accurately profiled using common sled-training equipment. Notably, the optimal loading conditions determined in this study (69-96% of BM, dependent on friction conditions) represent much greater resistance than current guidelines (~7-20% of BM). This method has potential value in quantifying individualized training parameters for optimized development of horizontal power.


Crystal Structures of the Plant Phospholipase A1 Proteins Reveal a Unique Dimerization Domain.
Phospholipase is an enzyme that hydrolyzes various phospholipid substrates at specific ester bonds and plays important roles such as membrane remodeling, as digestive enzymes, and the regulation of cellular mechanism. Phospholipase proteins are divided into following the four major groups according to the ester bonds they cleave off: phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase C (PLC), and phospholipase D (PLD). Among the four phospholipase groups, PLA1 has been less studied than the other phospholipases. Here, we report the first molecular structures of plant PLA1s: AtDSEL and CaPLA1 derived from Arabidopsis thaliana and Capsicum annuum, respectively. AtDSEL and CaPLA1 are novel PLA1s in that they form homodimers since PLAs are generally in the form of a monomer. The dimerization domain at the C-terminal of the AtDSEL and CaPLA1 makes hydrophobic interactions between each monomer, respectively. The C-terminal domain is also present in PLA1s of other plants, but not in PLAs of mammals and fungi. An activity assay of AtDSEL toward various lipid substrates demonstrates that AtDSEL is specialized for the cleavage of sn-1 acyl chains. This report reveals a new domain that exists only in plant PLA1s and suggests that the domain is essential for homodimerization.


"Cross" Supermicelles via the Hierarchical Assembly of Amphiphilic Cylindrical Triblock Comicelles.
Self-assembled "cross" architectures are well-known in biological systems (as illustrated by chromosomes, for example); however, comparable synthetic structures are extremely rare. Herein we report an in depth study of the hierarchical assembly of the amphiphilic cylindrical P-H-P triblock comicelles with polar (P) coronal ends and a hydrophobic (H) central periphery in a selective solvent for the terminal segments which allows access to "cross" supermicelles under certain conditions. Well-defined P-H-P triblock comicelles M(PFS-b-PtBA)-b-M(PFS-b-PDMS)-b-M(PFS-b-PtBA) (M = micelle segment, PFS = polyferrocenyldimethylsilane, PtBA = poly(tert-butyl acrylate), and PDMS = polydimethylsiloxane) were created by the living crystallization-driven self-assembly (CDSA) method. By manipulating two factors in the supermicelles, namely the H segment-solvent interfacial energy (through the central H segment length, L1) and coronal steric effects (via the PtBA corona chain length in the P segment, L2 related to the degree of polymerization DP2) the aggregation of the triblock comicelles could be finely tuned. This allowed a phase-diagram to be constructed that can be extended to other triblock comicelles with different coronas on the central or end segment where "cross" supermicelles were exclusively formed under predicted conditions. Laser scanning confocal microscopy (LSCM) analysis of dye-labeled "cross" supermicelles, and block "cross" supermicelles formed by addition of a different unimer to the arm termini, provided complementary characterization to transmission electron microscopy (TEM) and dynamic light scattering (DLS) and confirmed the existence of these "cross" supermicelles as kinetically stable, micron-size colloidally stable structures in solution.


Determining the absorption coefficient of absorbing thin films with optical waveguides.
A new simple method of determining the absorption coefficient of absorbing thin films is proposed as an application of the complex propagation constant of a guided wave in a thin film optical waveguide. This method was applied to both cases as examples: low index (polyurethane film top layer containing rhodamine 6G dye) and high index (evaporated ZnSe film top layer) absorbing top layers on the main glass guide. The absorption coefficients so determined were compared with the values given by Lambert's method.


Strong future increases in Arctic precipitation variability linked to poleward moisture transport.
The Arctic region is projected to experience amplified warming as well as strongly increasing precipitation rates. Equally important to trends in the mean climate are changes in interannual variability, but changes in precipitation fluctuations are highly uncertain and the associated processes are unknown. Here, we use various state-of-the-art global climate model simulations to show that interannual variability of Arctic precipitation will likely increase markedly (up to 40% over the 21st century), especially in summer. This can be attributed to increased poleward atmospheric moisture transport variability associated with enhanced moisture content, possibly modulated by atmospheric dynamics. Because both the means and variability of Arctic precipitation will increase, years/seasons with excessive precipitation will occur more often, as will the associated impacts.


Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain.
Reduction of the transmembrane chloride gradient in spinal lamina I neurons contributes to the cellular hyperexcitability producing allodynia and hyperalgesia after peripheral nerve injury. The resultant decrease in anion reversal potential (i.e. shift in Eanion to less negative potentials) reduces glycine/GABAA receptor-mediated hyperpolarization, but the large increase in membrane conductance caused by inhibitory input can nonetheless shunt concurrent excitatory input. Without knowing the relative contribution of hyperpolarization and shunting to inhibition's modulation of firing rate, it is difficult to predict how much net disinhibition results from reduction of Eanion. We therefore used a biophysically accurate lamina I neuron model to investigate quantitatively how changes in Eanion affect firing rate modulation. Simulations reveal that even a small reduction of Eanion compromises inhibitory control of firing rate because reduction of Eanion not only decreases glycine/GABAA receptor-mediated hyperpolarization, but can also indirectly compromise the capacity of shunting to reduce spiking. The latter effect occurs because shunting-mediated modulation of firing rate depends on a competition between two biophysical phenomena: shunting reduces depolarization, which translates into reduced spiking, but shunting also shortens the membrane time constant, which translates into faster membrane charging and increased spiking; the latter effect predominates when average depolarization is suprathreshold. Disinhibition therefore occurs as both hyperpolarization- and shunting-mediated modulation of firing rate are subverted by reduction of Eanion. Small reductions may be compensated for by increased glycine/GABAA receptor-mediated input, but the system decompensates (i.e. compensation fails) as reduction of Eanion exceeds a critical value. Hyperexcitability necessarily develops once disinhibition becomes incompensable. Furthermore, compensation by increased glycine/GABAA receptor-mediated input introduces instability into the system, rendering it increasingly prone to abrupt decompensation and even paradoxical excitation. Reduction of Eanion dramatically compromises the inhibitory control of firing rate and, if compensation fails, is likely to contribute to the allodynia and hyperalgesia associated with neuropathic pain. These data help explain the relative intractability of neuropathic pain and illustrate how it is important to choose therapies not only based on disease mechanism, but based on quantitative understanding of that mechanism.


Laparoscopy after previous laparotomy.
Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previous laparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.


What we know and what we don't know about perinatal Zika virus infection: a systematic review.
Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed. Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms ['Zika'] AND ['Perinatal Infection'] OR ['Congenital Infection'] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study. Expert commentary: ZIKV is a new teratogenic/neurotropic virus affecting fetuses. Many challenges are still far from being solved regarding the epidemiology, case definition, clinical and laboratory diagnosis, and preventive measures. An approach using 'omics' and new biomarkers for diagnosis, and a ZIKV-vaccine for treatment, might finally give us the tools to solve these challenges.


Systematic shifts in scaling behavior based on organizational strategy in universities.
To build better theories of cities, companies, and other social institutions such as universities, requires that we understand the tradeoffs and complementarities that exist between their core functions, and that we understand bounds to their growth. Scaling theory has been a powerful tool for addressing such questions in diverse physical, biological and urban systems, revealing systematic quantitative regularities between size and function. Here we apply scaling theory to the social sciences, taking a synoptic view of an entire class of institutions. The United States higher education system serves as an ideal case study, since it includes over 5,800 institutions with shared broad objectives, but ranges in strategy from vocational training to the production of novel research, contains public, nonprofit and for-profit models, and spans sizes from 10 to roughly 100,000 enrolled students. We show that, like organisms, ecosystems and cities, universities and colleges scale in a surprisingly systematic fashion following simple power-law behavior. Comparing seven commonly accepted sectors of higher education organizations, we find distinct regimes of scaling between a school's total enrollment and its expenditures, revenues, graduation rates and economic added value. Our results quantify how each sector leverages specific economies of scale to address distinct priorities. Taken together, the scaling of features within a sector along with the shifts in scaling across sectors implies that there are generic mechanisms and constraints shared by all sectors, which lead to tradeoffs between their different societal functions and roles. We highlight the strong complementarity between public and private research universities, and community and state colleges, that all display superlinear returns to scale. In contrast to the scaling of biological systems, our results highlight that much of the observed scaling behavior is modulated by the particular strategies of organizations rather than an immutable set of constraints.


Intelligent complementary sliding-mode control for LUSMS-based X-Y-theta motion control stage.
An intelligent complementary sliding-mode control (ICSMC) system using a recurrent wavelet-based Elman neural network (RWENN) estimator is proposed in this study to control the mover position of a linear ultrasonic motors (LUSMs)-based X-Y-theta motion control stage for the tracking of various contours. By the addition of a complementary generalized error transformation, the complementary sliding-mode control (CSMC) can efficiently reduce the guaranteed ultimate bound of the tracking error by half compared with the slidingmode control (SMC) while using the saturation function. To estimate a lumped uncertainty on-line and replace the hitting control of the CSMC directly, the RWENN estimator is adopted in the proposed ICSMC system. In the RWENN, each hidden neuron employs a different wavelet function as an activation function to improve both the convergent precision and the convergent time compared with the conventional Elman neural network (ENN). The estimation laws of the RWENN are derived using the Lyapunov stability theorem to train the network parameters on-line. A robust compensator is also proposed to confront the uncertainties including approximation error, optimal parameter vectors, and higher-order terms in Taylor series. Finally, some experimental results of various contours tracking show that the tracking performance of the ICSMC system is significantly improved compared with the SMC and CSMC systems.


Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.
Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.


Comments on "Accuracy of Raman lidar water vapor calibration and its applicability to long-term measurements".
In a recent publication, Leblanc and McDermid [Appl. Opt., 47, 5592 (2008)]APOPAI0003-693510.1364/AO.47.005592 proposed a hybrid calibration technique for Raman water vapor lidar involving a tungsten lamp and radiosondes. Measurements made with the lidar telescope viewing the calibration lamp were used to stabilize the lidar calibration determined by comparison with radiosonde. The technique provided a significantly more stable calibration constant than radiosondes used alone. The technique involves the use of a calibration lamp in a fixed position in front of the lidar receiver aperture. We examine this configuration and find that such a configuration likely does not properly sample the full lidar system optical efficiency. While the technique is a useful addition to the use of radiosondes alone for lidar calibration, it is important to understand the scenarios under which it will not provide an accurate quantification of system optical efficiency changes. We offer examples of these scenarios. Scanning of the full telescope aperture with the calibration lamp can circumvent most of these limitations. Based on the work done to date, it seems likely that the use of multiple calibration lamps in different fixed positions in front of the telescope may provide sufficient redundancy for long-term calibration needs. Further full-aperture scanning experiments, performed over an extended period of time, are needed to determine a "best practice" for the use of multiple calibration lamps in the hybrid technique.


Different time scales of motion integration for anticipatory smooth pursuit and perceptual adaptation.
When repeatedly exposed to moving stimuli, the oculomotor system elicits anticipatory smooth pursuit (ASP) eye movements, even before the stimulus moves. ASP is affected oppositely to perceptual speed judgments of repetitive moving stimuli: After a sequence of fast stimuli, ASP velocity increases, whereas perceived speed decreases. These two effects--perceptual adaptation and oculomotor priming--could result from adapting a single common internal speed representation that is used for perceptual comparisons and for generating ASP. Here we test this hypothesis by assessing the temporal dependence of both effects on stimulus history. Observers performed speed discriminations on moving random dot stimuli, either while pursuing the movement or maintaining steady fixation. In both cases, responses showed perceptual adaptation: Stimuli preceded by fast speeds were perceived as slower, and vice versa. To evaluate oculomotor priming, we analyzed ASP velocity as a function of average stimulus speed in preceding trials and found strong positive dependencies. Interestingly, maximal priming occurred over short stimulus histories (∼two trials), whereas adaptation was maximal over longer histories (∼15 trials). The temporal dissociation of adaptation and priming suggests different underlying mechanisms. It may be that perceptual adaptation integrates over a relatively long period to robustly calibrate the operating range of the motion system, thereby avoiding interference from transient changes in stimulus speed. On the other hand, the oculomotor system may rapidly prime anticipatory velocity to efficiently match it to that of the pursuit target.


Expansion of Foxp3(+) T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge.
Candida albicans remains the fungus most frequently associated with nosocomial bloodstream infection. In disseminated candidiasis, the role of Foxp3(+) regulatory T (Treg) cells remains largely unexplored. Our aims were to characterize Foxp3(+) Treg-cell activation in a murine intravenous challenge model of disseminated C. albicans infection, and determine the contribution to disease. Flow cytometric analyses demonstrated that C. albicans infection drove in vivo expansion of a splenic CD4(+) Foxp3(+) population that correlated positively with fungal burden. Depletion from Foxp3(hCD2) reporter mice in vivo confirmed that Foxp3(+) cells exacerbated fungal burden and inflammatory renal disease. The CD4(+) Foxp3(+) population expanded further after in vitro stimulation with C. albicans antigens (Ags), and included at least three cell types. These arose from proliferation of the natural Treg-cell subset, together with conversion of Foxp3(-) cells to the induced Treg-cell form, and to a cell type sharing effector Th17-cell characteristics, expressing ROR-γt, and secreting IL-17A. The expanded Foxp3(+) T cells inhibited Th1 and Th2 responses, but enhanced Th17-cell responses to C. albicans Ags in vitro, and in vivo depletion confirmed their ability to enhance the Th17-cell response. These data lead to a model for disseminated candidiasis whereby expansion of Foxp3(+) T cells promotes Th17-cell responses that drive pathology.


Symmetric Electrodes for Electrochemical Energy-Storage Devices.
Increasing environmental problems and energy challenges have so far attracted urgent demand for developing green and efficient energy-storage systems. Among various energy-storage technologies, sodium-ion batteries (SIBs), electrochemical capacitors (ECs) and especially the already commercialized lithium-ion batteries (LIBs) are playing very important roles in the portable electronic devices or the next-generation electric vehicles. Therefore, the research for finding new electrode materials with reduced cost, improved safety, and high-energy density in these energy storage systems has been an important way to satisfy the ever-growing demands. Symmetric electrodes have recently become a research focus because they employ the same active materials as both the cathode and anode in the same energy-storage system, leading to the reduced manufacturing cost and simplified fabrication process. Most importantly, this feature also endows the symmetric energy-storage system with improved safety, longer lifetime, and ability of charging in both directions. In this Progress Report, we provide the comprehensive summary and comment on different symmetric electrodes and focus on the research about the applications of symmetric electrodes in different energy-storage systems, such as the above mentioned SIBs, ECs and LIBs. Further considerations on the possibility of mass production have also been presented.


Effectiveness of isolation policies in schools: evidence from a mathematical model of influenza and COVID-19.
Non-pharmaceutical interventions such as social distancing, school closures and travel restrictions are often implemented to control outbreaks of infectious diseases. For influenza in schools, the Center of Disease Control (CDC) recommends that febrile students remain isolated at home until they have been fever-free for at least one day and a related policy is recommended for SARS-CoV-2 (COVID-19). Other authors proposed using a school week of four or fewer days of in-person instruction for all students to reduce transmission. However, there is limited evidence supporting the effectiveness of these interventions. We introduced a mathematical model of school outbreaks that considers both intervention methods. Our model accounts for the school structure and schedule, as well as the time-progression of fever symptoms and viral shedding. The model was validated on outbreaks of seasonal and pandemic influenza and COVID-19 in schools. It was then used to estimate the outbreak curves and the proportion of the population infected (attack rate) under the proposed interventions. For influenza, the CDC-recommended one day of post-fever isolation can reduce the attack rate by a median (interquartile range) of 29 (13-59)%. With 2 days of post-fever isolation the attack rate could be reduced by 70 (55-85)%. Alternatively, shortening the school week to 4 and 3 days reduces the attack rate by 73 (64-88)% and 93 (91-97)%, respectively. For COVID-19, application of post-fever isolation policy was found to be less effective and reduced the attack rate by 10 (5-17)% for a 2-day isolation policy and by 14 (5-26)% for 14 days. A 4-day school week would reduce the median attack rate in a COVID-19 outbreak by 57 (52-64)%, while a 3-day school week would reduce it by 81 (79-83)%. In both infections, shortening the school week significantly reduced the duration of outbreaks. Shortening the school week could be an important tool for controlling influenza and COVID-19 in schools and similar settings. Additionally, the CDC-recommended post-fever isolation policy for influenza could be enhanced by requiring two days of isolation instead of one.


Facilitative priority effects drive parasite assembly under coinfection.
Host individuals are often coinfected with diverse parasite assemblages, resulting in complex interactions among parasites within hosts. Within hosts, priority effects occur when the infection sequence alters the outcome of interactions among parasites. Yet, the role of host immunity in this process remains poorly understood. We hypothesized that the host response to the first infection could generate priority effects among parasites, altering the assembly of later-arriving strains during epidemics. We tested this by infecting sentinel host genotypes of Plantago lanceolata with strains of the fungal parasite Podosphaera plantaginis and measuring susceptibility to subsequent infection during experimental and natural epidemics. In these experiments, prior infection by one strain often increased susceptibility to other strains, and these facilitative priority effects altered the structure of parasite assemblages, but this effect depended on host genotype, host population and parasite genotype. Thus, host genotype, spatial structure and priority effects among strains all independently altered parasite assembly. Using a fine-scale survey and sampling of infections on wild hosts in several populations, we then identified a signal of facilitative priority effects, which altered parasite assembly during natural epidemics. Together, these results provide evidence that within-host priority effects of early-arriving strains can drive parasite assembly, with implications for how strain diversity is spatially and temporally distributed during epidemics.