Assistance dogs provide a useful behavioral model to enrich communicative skills of assistance robots.
These studies are part of a project aiming to reveal relevant aspects of human-dog interactions, which could serve as a model to design successful human-robot interactions. Presently there are no successfully commercialized assistance robots, however, assistance dogs work efficiently as partners for persons with disabilities. In Study 1, we analyzed the cooperation of 32 assistance dog-owner dyads performing a carrying task. We revealed typical behavior sequences and also differences depending on the dyads' experiences and on whether the owner was a wheelchair user. In Study 2, we investigated dogs' responses to unforeseen difficulties during a retrieving task in two contexts. Dogs displayed specific communicative and displacement behaviors, and a strong commitment to execute the insoluble task. Questionnaire data from Study 3 confirmed that these behaviors could successfully attenuate owners' disappointment. Although owners anticipated the technical competence of future assistance robots to be moderate/high, they could not imagine robots as emotional companions, which negatively affected their acceptance ratings of future robotic assistants. We propose that assistance dogs' cooperative behaviors and problem solving strategies should inspire the development of the relevant functions and social behaviors of assistance robots with limited manual and verbal skills.


Managing lung disease in late life: a new approach.
Advanced pulmonary disease (APD), a progressive, incurable condition, ultimately leading to death, is associated with significant, distressing symptoms. This paper reviews how the hospice approach to care, with its emphasis on treating those symptoms causing the patient the most distress, might be used by physicians in the outpatient setting to improve the patient's quality of life. Important aspects of care include management of hypoxia, malnutrition, osteoporosis, adverse drug reactions, and, especially, the symptomatic relief of dyspnea. Relief of emotional symptoms (depression, anxiety, panic) is also discussed.


Digital electrospray for controlled deposition.
Many novel functional structures are now fabricated by controlled deposition as a maskless, bottom-up fabrication technique. These applications require rapid and precise deposition of minute amounts of solutions/suspensions or their ultimate particle products in predefined patterns. The electrospray is a promising alternative to the commonly used inkjet printing because it can easily handle highly viscous liquid, avoid high shear rates, and has low risk of clogging. We demonstrate a proof-of-concept digital electrospray. This system consists of a 61-nozzle array microfabricated in silicon and a 61-element digital extractor fabricated using flexible polyimide substrates. "Digital" refers to the state of each electrospray source that can be tuned either on or off independently and responsively. We showed a resolution of 675 mum and a response frequency up to 100 Hz. With similar design and industry standard fabrication procedures, it is feasible to scale up the system to O(1000) sources with spatial resolution better than 250 mum and a O(kHz) response frequency. The latter is controlled by the viscous damping time.


The effect of ferrous-chelating hairtail peptides on iron deficiency and intestinal flora in rats.
Chelating agents, such as small peptides, can decrease free iron content and increase iron bioavailability. They may have promising therapeutic potential and may prevent the pro-oxidant effects of low molecular weight iron. Hairtail is a species of fish that is rich in easily digestible proteins. We extended this strategy for iron delivery by using an enzymatic hydrolysate of hairtail as the chelating agent and found that the ferrous-chelating hairtail peptides have anti-anaemic activity in Sprague-Dawley rats with anaemia. The anti-anaemic activity of ferrous-chelating hairtail peptides prepared by enzymatic hydrolysis of the hairtail and ferrous chelation was studied in rat models of iron deficiency anaemia. After the end of the 35 d experiment, we noted significant differences in haemoglobin, mean corpuscular volume, haemoglobin distribution width, and ferritin concentrations between those animals supplemented with ferrous-chelating hairtail peptides and FeSO4 and healthy animals. There were no negative side effects on the animals' growth or behaviour. There was no obvious inflammation in the intestinal mucosa lamina propria and no unbalance of intestinal flora. The novel ferrous-chelating hairtail peptides may be a suitable fortificant for improving iron-deficiency status. Our findings demonstrated that this multi-tracer technique has many applications in nutritional research. © 2015 Society of Chemical Industry.


Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion.
The nuclear chromatin structure confines the movement of large macromolecular complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm assemble in the nucleoplasm and must reach the nuclear membranes for egress. Previous studies concluded that nuclear herpesvirus capsid motility is active, directed, and based on nuclear filamentous actin, suggesting that large nuclear complexes need metabolic energy to escape nuclear entrapment. However, this hypothesis has recently been challenged. Commonly used microscopy techniques do not allow the imaging of rapid nuclear particle motility with sufficient spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we dubbed a ring-sheet, to image and track viral capsids with high temporal and spatial resolution. We do not find any evidence for directed transport. Instead, infection with different herpesviruses induced an enlargement of interchromatin domains and allowed particles to diffuse unrestricted over longer distances, thereby facilitating nuclear egress for a larger fraction of capsids.


Feedbacks, climate sensitivity and the limits of linear models.
The term 'feedback' is used ubiquitously in climate research, but implies varied meanings in different contexts. From a specific process that locally affects a quantity, to a formal framework that attempts to determine a global response to a forcing, researchers use this term to separate, simplify and quantify parts of the complex Earth system. We combine new model results with a historical and educational perspective to organize existing ideas around feedbacks and linear models. Our results suggest that the state- and forcing-dependency of feedbacks are probably not appreciated enough, and not considered appropriately in many studies. A non-constant feedback parameter likely explains some of the differences in estimates of equilibrium climate sensitivity from different methods and types of data. Clarifying the value and applicability of the linear forcing feedback framework and a better quantification of feedbacks on various timescales and spatial scales remains a high priority in order to better understand past and predict future changes in the climate system.


Enhanced degradation and toxicity reduction of dihexyl phthalate by Fusarium oxysporum f. sp. pisi cutinase.
This research aims to investigate the efficiency of two lipolytic enzymes--fungal cutinase and yeast esterase--upon the biodegradation of dihexyl phthalate (DHP). During the enzymatic degradation of DHP dissolved in methanol, several degradation products were detected and their time-course changes were monitored using GC/MS. The DHP-degradation rate of cutinase was surprisingly high; i.e. almost 70% of the initial DHP (500 mg l(-1)) was decomposed within 4.5 h. Although the same amount of esterase was employed, more than 85% of the DHP remained after 3 days. Almost all the DHP was converted by cutinase into 1,3-isobenzofurandione (IBF), whereas hexyl methyl phthalate and IBF were abundantly produced by esterase. In addition, the toxicities of the DHP-degraded products by esterase were evaluated using various recombinant bioluminescent bacteria, which caused oxidative and protein damage, whereas the hydrolysis products from cutinase never caused any cellular damage in the methanol-containing reaction system. Cutinase starts to act as a DHP-degrader much earlier and faster than esterase, with high stability in ester-hydrolytic activity, therefore a plausible approach to the practical application of cutinase for DHP degradation in the DHP-contaminated environments may be possible. This study describes the enhanced degradation and detoxification of DHP using Fusarium oxysporum f. sp. pisi cutinase.


Longitudinal impact of interprofessional education on attitudes, skills and career trajectories: a protocol for a quasi-experimental study in New Zealand.
Interprofessional practice is recognised as an important element of safe and effective healthcare. However, few studies exist that evaluate how preregistration education contributes to interprofessional competencies, and how these competencies develop throughout the early years of a health professional's career. This quasiexperimental study will gather longitudinal data during students' last year of preregistration training and their first 3 years of professional practice to evaluate the ongoing development of interprofessional competencies and the influence that preregistration education including an explicit interprofessional education (IPE) programme may have on these. Participants are students and graduates from the disciplines of dentistry, dietetics, medicine, nursing, occupational therapy, oral health, pharmacy and physiotherapy recruited before their final year of study. A subset of these students attended a 5-week IPE immersion programme during their final year of training. All data will be collected via five written or electronic surveys completed at 12-month intervals. Each survey will contain the Attitudes Towards Health Care Teams Scale and the Team Skills Scale, as well as quantitative and free-text items to explore vocational satisfaction, career trajectories and influences on these. Students who attend the IPE programme will complete additional free-text items to explore the effects of this programme on their careers. Quantitative analysis will compare scores at each time point, adjusted for baseline scores, for graduates who did and did not participate in the IPE programme. Associations between satisfaction data and discipline, professional setting, location and IPE participation will also be examined. Template analysis will explore free-text themes related to influences on career choices including participation in preregistration IPE. This study has received approval from the University of Otago Ethics Committee (D13/019). Results will be disseminated through peer-reviewed publications, conferences and stakeholder reports. Findings will inform future IPE developments and health workforce planning.


Small scale sandwich enzyme immunoassay for human chorionic gonadotropin using a new micro-transferable plastic bead as solid phase.
This paper describes a highly sensitive small scale enzyme immunoassay for human chorionic gonadotropin (hCG) in pregnancy urine using a microtransferable plastic bead (MTPB) as solid phase. Results of the present method for determination of 40 samples of pregnancy urine correlated well with those of the commercial radioimmunoassay and a better precision was achieved. This solid phase method may be widely applied to the immunoassay of small volumes.


Extreme hypercapnia is not a long-term prognostic factor after near-fatal asthma: a 12-year follow-up study.
Some patients experiencing near-fatal asthma present with extreme hypercapnia (PaCO2 > or = 100 mm Hg), whereas others do not. The influence of this factor on short- and long-term outcome and quality of life in these patients is still unknown. A series of 39 consecutive patients who had had an episode of near-fatal asthma between 1978 and 1992 were followed up. Long-term outcome and quality of life of the 12 patients who had experienced extreme hypercapnia were compared with those of the 27 patients who had not. Four patients died, but only 1 from asthma. Three patients were lost to follow-up. The remaining 32 patients had a median observation period of 12.7 years. The hypercapnic patients did not significantly differ from the others in past asthma history, subsequent hospitalizations, medication needs, pulmonary function tests, quality of life and impairment/disability. In the event of subsequent near-fatal asthma attacks, they tended to present with hypercapnia levels similar to those observed during the first episode. Extreme hypercapnia in near-fatal asthma tended to recur, but is not an aggravating long-term prognostic factor. Targeted surveillance of these high-risk patients should make it possible to reduce relapses and death rates from asthma.


Oncologists' influence on receipt of adjuvant chemotherapy: does it matter whom you see for treatment of curable breast cancer?
We know little about whether it matters which oncologist a breast cancer patient sees with regard to receipt of chemotherapy. We examined oncologists' influence on use of recurrence score (RS) testing and chemotherapy in the community. We identified 7810 women with stages 0-II breast cancer treated in 2013-15 through the SEER registries of Georgia and Los Angeles County. Surveys were sent 2 months post-surgery, (70% response rate, n = 5080). Patients identified their oncologists (n = 504) of whom 304 responded to surveys (60%). We conducted multi-level analyses on patients with ER-positive HER2-negative invasive disease (N = 2973) to examine oncologists' influence on variation in RS testing and chemotherapy receipt, using patient and oncologist survey responses merged to SEER data. Half of patients (52.8%) received RS testing and 27.7% chemotherapy. One-third (35.9%) of oncologists treated >50 new breast cancer patients annually; mean years in practice was 15.8. Oncologists explained 17% of the variation in RS testing but little of the variation in chemotherapy receipt (3%) controlling for clinical factors. Patients seeing an oncologist who was one standard deviation above the mean use of RS testing had over two-times higher odds of receiving RS (2.47, 95% CI 1.47-4.15), but a parallel estimate of the association of oncologist with the odds of receiving chemotherapy was much smaller (1.39, CI 1.03-1.88). Clinical algorithms have markedly reduced variation in chemotherapy use across oncologists. Oncologists' large influence on variation in RS use suggests that they variably seek tumor profiling to inform treatment decisions.


Psychosocial determinants of adherence to highly active antiretroviral therapy among injection drug users in Vancouver.
Sub-optimal adherence to highly active antiretroviral therapy (HAART) among injection drug users (IDUs) is a significant concern. As such, there is an urgent need to identify psychosocial determinants of adherence that can be incorporated into interventions designed to promote optimal adherence. To identify psychosocial determinants of adherence to HAART, as well as self-reported reasons for missing doses of HAART among HIV-infected IDUs. We developed an eight-item adherence self-efficacy scale comprised of two sub-scales: adherence efficacy and self-regulatory efficacy. We examined correlates between adherence self-efficacy, outcome expectations, socio-demographic characteristics, drug use and risk behaviours, social support and HAART adherence among 108 HIV-infected participants in the Vancouver Injection Drug Users Study (VIDUS). Pharmacy-based adherence to HAART was obtained through a confidential record linkage to the province of British Columbia's HIV/AIDS Drug Treatment Program. Participants were defined as adherent if they picked-up 95% of their HAART prescriptions. Participants were also asked to indicate reasons for missing doses of HAART. Logistic regression was used to identify the factors independently associated with adherence to HAART. Seventy-one (66%) HIV-infected IDUs were less than 95% adherent. Forgetting was the most frequently cited reason (27%) for missing doses of HAART. Factors independently associated with adherence to HAART included adherence efficacy expectations [OR=1.8 (95% CI: 1.0-3.1); P=0.039] and negative outcome expectations [OR=0.8 (95% CI: 0.7-0.9); P=0.027]. We found low rates of adherence to HAART among IDUs. Psychological constructs derived from self-efficacy theory are highly germane to the understanding of adherence behaviour, and interventions that address these constructs should be developed and tested among HIV-infected drug users.


Expression of the cation transporter McHKT1 in a halophyte.
From the ice plant, Mesembryanthemum crystallinum, McHKT1 was isolated encoding a protein 41-61% identical to other plant HKT1-like sequences previously described as potassium or sodium/potassium transporters. McHKT1 acts as a potassium transporter in yeast with specificity similar to that of wheat HKT1. In Xenopus oocytes it transports cations with a specificity Rb+ > Cs+ > [K+ = Na+ = Li+]. McHKT1 is exclusively localized to the plasma membrane. The isoform isolated is most highly expressed in leaves and is present in stems, flowers and seed pods but absent from the root where, according to immunological data, a second isoform exists which does not cross-hybridize with the leaf form in RNA blots at high stringency. McHKT1 transcript amounts increase during the first 6-10 h of stress and then decline to pre-stress levels with kinetics reminiscent of the initial influx of sodium into this halophyte. Immunocytological localization showed strong signals in the leaf vasculature and surrounding mesophyll cells but low-intensity signals are also detected in other cell types. In roots, McHKT is mainly confined to endodermis and stele. Possible functions of McHKT1 in ion homeostasis in the halophytic ice plant are discussed.


N,N'-Bis(4-chloro-phen-yl)maleamide.
In the crystal of the title compound, C(16)H(12)Cl(2)N(2)O(2), the two C=O groups are anti to each other, while one of them is syn and the other is anti to their adjacent C-H bonds. The two benzene rings are oriented at an inter-planar angle of 56.4 (1)°, while the dihedral angles between the central amide group (N-C-C-C-C-N) and these rings are 3.6 (1) and 54.1 (1)°. An intra-molecular N-H⋯O hydrogen bond occurs. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into infinite chains along the a axis.


Computed tomographic diagnosis of appendicitis within a spigelian hernia.
A Spigelian hernia is a rare abdominal wall hernia diagnosed with ultrasonography or computed tomography. We report the first case of acute appendicitis within a Spigelian hernia diagnosed by computed tomography.


Oxidative Stress and Inflammatory Markers PTX3, CypA, and HB-EGF: How Are They Linked in Patients With STEMI?
We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = -0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a "metabolic-oxidative stress factor" comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values.


Unveiling One-Dimensional Supramolecular Structures Formed through π-π Stacking of Phenothiazines by Differential Pulse Voltammetry.
Organic-based nanomaterials can be self-assembled by strong and directional intermolecular forces such as π-π interactions. Experimental information about the stability, size, and geometry of the formed structures is very limited for species that easily aggregate, even at very low concentrations. Differential pulse voltammetry (DPV) can unveil the formation, growth, and also the stability window of ordered, one-dimensional, lamellar self-aggregates formed by supramolecular π stacking of phenothiazines at micromolar (10-6 mol L-1 ) concentrations. The self-diffusion features of the species at different concentrations are determined by DPV and used to probe the π staking process through the concept of the frictional resistance. It is observed that toluidine blue and methylene blue start to self-aggregate around 9 μmol L-1 , and that the self-aggregation process occurs by one-dimensional growth as the concentration of the phenothiazines is increased up to around 170 μmol L-1 for toluidine blue and 200 μmol L-1 for methylene blue. At higher concentrations, the aggregation process leads to structures with lower anisometry.


A novel technique for in situ calibration of the C-2W electromagnetic neutral particle analyzer utilizing machine learning.
In TAE Technologies' current experimental device, C-2W, neutral beam injection creates a large fast ion population that sustains a field-reversed configuration (FRC) plasma. Diagnosis of these fast ions is therefore critical for understanding the behavior of the FRC. Neutral Particle Analyzers (NPAs) are used to measure the energy spectrum of fast ions that charge exchange on background or beam neutrals and are lost from the plasma. To ensure correct diagnosis of the fast ion population, a calibration check of the NPAs was performed. A novel, generally applicable method for an in situ relative calibration of diagnostics on an unknown source with a small dataset was developed. The method utilizes a machine learning technique, Generalized Additive Models (GAMs), to reconstruct the diagnostic source distribution, and Stochastic Gradient Descent (SGD) to determine the NPA channel calibration factors. The results on both synthetic and experimental datasets are presented.


Molecular structure of the dihydropyridazinone cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-pyridazinyl)- 2H-indol-2-one, a potent inhibitor of cyclic AMP phosphodiesterase.
The cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3- pyridazinyl)-2H-indol-2-one (1, LY195115) is a potent, competitive inhibitor (Ki = 80 nM) of sarcoplasmic reticulum derived phosphodiesterase (SR-PDE). Moreover, the compound is a potent positive inotrope both in vitro and in vivo. To assist further cardiotonic drug-design studies, we have mapped the three-dimensional structure of 1 using X-ray crystallography. From a global viewpoint, this drug was essentially planar, but two small regions of nonplanarity were apparent. These involved the geminal methyl substituents in the indol-2-one moiety and the C5' methylene unit of the dihydropyridazinone ring. Because of our previous studies involving the bipyridine cardiotonics amrinone and milrinone, the conformational relationship between the plane of the phenyl ring and the horizontal symmetry plane defined by N2', C3', and C4' of 1 was of particular interest. The C6-C5-C3'-C4' dihedral angle was -2.7 degrees, whereas the C6-C5-C3'-N2' dihedral angle was 174.6 degrees. Therefore the two rings maintain a high degree of coplanarity. Compound 4, the congener of 1 possessing a completely unsaturated pyridazinone ring was also studied. In terms of inotropic activity, this compound, devoid of any puckering in the pyridazinone moiety, was equipotent with 1. Methyl substitution at the 4-position of the dihydropyridazinone and pyridazinone rings provided disparate results. Compound 2, the 4-methyl analogue of 1, was 2-fold more potent than 1, and the methyl substituent probably caused only minor perturbations in overall molecular topology. However 5, the 4-methyl analogue of the pyridazinone 4, was 4.4-fold less active than 4, perhaps as a result of methyl-induced molecular nonplanarity.


Genetic polymorphisms underlying the skeletal Class III phenotype.
Our goal was to verify the association between candidate polymorphisms and skeletal Class III malocclusion in a well-characterized homogeneous sample set. Thirty-five single-nucleotide polymorphisms were studied from 10 candidate loci in 54 Class III subjects and 120 controls. Skeletal Class III characteristics included ANB angle less than 0°, SNB angle greater than 83° (mandibular prognathism), SNA angle less than 79° (maxillary deficiency), Class III molar relationship, and negative overjet. Inclusion criteria for the controls were ANB angle between 0° and 4°, Class I molar relationship, and normal overjet. Chi-square and Fisher exact tests and principal component (PC) analysis were used to determine overrepresentation of marker alleles with alpha of 0.05. Odds ratios and 95% confidence intervals were calculated. MYO1H (rs10850110 A<G) (P <0.01; odds ratio, 7.44 [4.02-13.77]) was associated with an increased risk for the mandibular prognathism phenotype. These results were confirmed by PC analysis, which showed 4 PCs representing the sample variations (PC1, 37.24%; PC2, 20.02%; PC3, 12.18%; and PC4, 11.40%), and PC1 was associated with MYO1H (P <0.001). We also found by PC analysis associations between MYO1H (P <0.001) and GHR (rs2973015 A>G) (P = 0.001) with PC2 and between FGF10 (rs593307 A<G) (P = 0.001) with PC4. Polymorphism in MYO1H could be used as a marker for genetic susceptibility to Class III malocclusion with mandibular prognathism, and polymorphisms in GHR and FGF were associated with maxillomandibular discrepancies. This study may contribute to improved diagnosis and further research assessing possible differences in treatment responses based on genetic polymorphisms.


Metabotropic glutamate receptor 7: at the interface of cognition and emotion.
Understanding the complex interaction between stress and genetics that leads to the manifestation of disorders such as depression, anxiety, and cognitive dysfunction is one of the key areas of research in modern neuroscience. Growing evidence suggests that the glutamatergic system may be a relevant therapeutic target for such disorders. Glutamate is the neurotransmitter at the vast majority of excitatory synapses in the brain, and metabotropic glutamate (mGlu) receptor subtypes (mGlu(1) receptor-mGlu(8) receptor) act as important pre- and postsynaptic regulators of neurotransmission in the central nervous system (CNS), providing a mechanism by which fast synaptic responses through ligand-gated cation channels can be fine-tuned. Thus mGlu receptors are poised to participate in a wide variety of functions of the CNS. The presynaptic mGlu(7) receptor shows the highest evolutionary conservation within the family and it is thought to regulate neurotransmitter release. The mGlu(7) receptor is also the most widely distributed of the presynaptic mGlu receptors and is present at a broad range of synapses that are postulated to be critical for both normal CNS function and a range of psychiatric and neurological disorders. A growing body of evidence suggests that the mGlu(7) receptor is a key player in shaping synaptic responses at glutamatergic synapses as well as being a key regulator of inhibitory GABAergic transmission. The development of selective pharmacological and genetic tools has allowed for the unravelling of mGlu(7) receptor function in a host of physiological and behavioural processes. Knockout mice and siRNA knockdown has pointed to a role of the mGlu(7) receptor in anxiety, extinction of fear and aversion learning, spatial memory and the hormonal response to stress. In addition, these studies are largely supported by pharmacological manipulation of mGlu(7) receptor using the selective modulator N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), although paradoxical effects with this agonist have also emerged. Together these data suggest that the mGlu(7) receptor is an important regulator of glutamatergic function, of fear and aversion and cognition and thus this receptor represents an innovative therapeutic target for stress-related disorders at the interface of cognition and anxiety.


Influence of Epstein-Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma.
To assess the effects of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.


Sensitivity and specificity of the Neuropsychological Impairment Scale (NIS).
Evaluated the sensitivity and specificity of the Neuropsychological Impairment Scale (NIS) using the Halstead Impairment Index as the criterion (N = 41). Acceptable values are achieved by both NIS and Trailmaking Tests when used separately. When used "in parallel," higher classification rates are achieved. This combination of the NIS, a neuropsychological symptom self-report measure, in combination with a performance task ( Trailmaking Tests) permits observation of behavioral deficit while it provides additional symptom information with which to pursue more extensive inquiry.


Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies.
Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking.


Cu-Catalyzed Aminodifluoroalkylation of Alkynes and α-Bromodifluoroacetamides.
The copper-catalyzed highly regioselective aminodifluoroalkylation of alkynes and α-bromodifluoroacetamides was realized for the first time. With this method, 3,3-difluoro-1H-pyrrol-2(3H)-ones were constructed in a single step from various alkynes and α-bromodifluoroacetamides substrates without using any extra oxidant.


Effect of iron status on DMT1 expression in duodenal enterocytes from beta2-microglobulin knockout mice.
Divalent metal transporter I (DMT1) is thought to be involved in transport of iron across the apical cell membrane of villus duodenal cells. To determine its role in hereditary hemochromatosis (HH), we used beta2-microglobulin knockout (B2M-/-) mice that accumulate iron as in HH. The B2M-/- and control C57BL/6 (B2M+/+) mice were fed diets with different iron contents. Increasing the iron availability increased plasma iron levels in both B2M+/+ and B2M-/- mice. Reducing the iron availability decreased the plasma iron concentration in B2M+/+ mice but was without effect on plasma iron in B2M-/- mice. DMT1 was not detectable in mice fed normal or iron-loaded diets when using immunohistochemistry. In Western blots, however, the protein was consistently observed regardless of the dietary regimen. DMT1 expression was increased to the same extent in B2M+/+ and B2M-/- mice when fed an iron-poor diet. In both strains of mice fed an iron-poor diet, DMT1 was evenly distributed in the differentiated enterocytes from the base to the tip of the villi but was absent from the crypts of Lieberkühn. These data suggest that the observed effects were due to the state of iron deficiency in mucosal cells rather than genetic defect.


Update on pediatric sepsis: a review.
Sepsis is one of the leading causes of mortality among children worldwide. Unfortunately, however, reliable evidence was insufficient in pediatric sepsis and many aspects in clinical practice actually depend on expert consensus and some evidence in adult sepsis. More recent findings have given us deep insights into pediatric sepsis since the publication of the Surviving Sepsis Campaign guidelines 2012. New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. Quality improvement initiatives of pediatric "sepsis bundles" were reported to be successful in clinical outcomes by several centers. Moreover, a recently published global epidemiologic study (the SPROUT study) did not only reveal the demographics, therapeutic interventions, and prognostic outcomes but also elucidated the inappropriateness of the current definition of pediatric sepsis. With these updated knowledge, the management of pediatric sepsis would be expected to make further progress. In addition, it is meaningful that the fundamental data on which future research should be based were established through the SPROUT study.


Five steps for delivering an effective and educational lecture.
This article highlights 5 essential components of creating and effectively delivering an educational lecture in the medical arena. Optimizing the transmission of knowledge is ideal for fostering an atmosphere that is conducive to all learners and helps physicians pursue their goal of lifelong learning.


Microfabricated in-channel structured polydimethylsiloxane microfluidic system for a lab-on-a-chip.
In this paper, the fabrication of microfluidic system integrated with micropump and microvalve on the same substrate and its high performance are described. The microfabricated microfluidic system has been optimized for application in capillary electrophoresis-electrochemical detector (CE-ECD), polymerase chain reaction (PCR) and microcantilever. The system is realized by means of a polydimethylsiloxane (PDMS)-glass chip and indium tin oxide heater. The pumping rates of the proposed micropump are measured as functions of the frequency and the duty-ratio of applied voltage. The performances of the microvalves are characterized under the on/off alternation with the applied power of the indium tin oxide (ITO) heater. The flow rate gradually decreases as the applied heater power increase. The optimized membrane thickness for microfluidic system is 350 microm. At this condition, the power of the cut-off flow in microvalve is 400 mW and the 70 nl/min of maximum pumping rate is observed at a duty ratio of 4% and a frequency of 4 Hz for the applied pulse power.


Circulating methylated DNA.
Early detection of cancer would facilitate better management of patients, because survival is greatly affected by stage of presentation. Circulating nucleic acids represent a biomarker that might be used in the early detection of cancer. In addition, such biomarkers could potentially be used to follow the progression of patients with cancer. DNA methylation of the promoter region CpG islands of genes represents one such nucleic acid-based marker, and possesses some advantages over other approaches. These include the stability of DNA as a molecule, the ability to detect such changes using simple polymerase chain reaction-based approaches, and the potential for methylated DNA to be preferentially present in nucleosomes in plasma or serum. These factors are presented and their impact on the detection of methylated DNA circulating in the bloodstream is demonstrated.


Orthogonal patterning of multiple biomolecules using an organic fluorinated resist and imprint lithography.
The ability to spatially deposit multiple biomolecules onto a single surface with high-resolution while retaining biomolecule stability and integrity is critical to the development of micro- and nanoscale biodevices. While conventional lithographic patterning methods are attractive for this application, they typically require the use of UV exposure and/or harsh solvents and imaging materials, which may be damaging to fragile biomolecules. Here, we report the development of a new patterning process based on a fluorinated patterning material that is soluble in hydrofluoroether solvents, which we show to be benign to biomolecules, including proteins and DNA. We demonstrate the implementation of these materials into an orthogonal processing system for patterning multibiomolecule arrays by imprint lithography at room temperature. We further showcase this method's capacity for fabricating patterns of receptor-specific ligands for fundamental cell studies.


Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology.
The potential of CD4+ T cells for cross-recognition of self and foreign Ags has important implications for the understanding of thymic selection, lymphocyte survival, and the occurrence of autoimmune diseases. Here, we define the extensive flexibility of Ag recognition for three human CD4+ autoreactive T cell clones (TCC) by using ligands with single and multiple amino acid (aa) substitutions. Our results demonstrate that the spectrum of tolerated ligands and the resulting stimulatory potency of peptides for a TCC can be predicted by the relative influence of each aa. Using this approach, we have identified stimulatory ligands not sharing a single aa in corresponding positions with the Ag used to establish the TCC. These results argue for an independent contribution of each aa in the peptide sequence to the affinity of the MHC/peptide complex to the TCR.


Absence of correlation between cytotoxicity and drug transport by P-glycoprotein in clinical leukemic cells.
Development of resistance to cytotoxic agents is a common problem in the treatment of acute leukemia. In cell lines having multidrug resistance (MDR) phenotype, a decrease in the intracellular accumulation of drugs has been closely related to the overexpression of P-glycoprotein/mdr1 genes. We analyzed the relationship between the cytotoxicity of adriamycin (ADR) in vitro, intracellular accumulation of ADR, and the expression of P-glycoprotein on fresh leukemic cells from 19 patients at their initial presentation and from 9 relapsed patients. Pretreatment patients showed significantly higher ratio of complete remission than relapsed patients, and mean value of IC50 for adriamycin in initial presentation was higher than at relapse. But we found no significant relationship between in vitro cytotoxicity and drug transport. In addition, only 2 of the 5 relapsed patients examined by monoclonal antibody C219 expressed the P-glycoprotein. These results suggest that the acquisition of clinical drug resistance may involve various mechanisms other than the reduction of drug accumulation with P-glycoprotein expression.


Exploration of Inflammatory Bowel Disease in Mice: Chemically Induced Murine Models of Inflammatory Bowel Disease (IBD).
Inflammatory bowel disease (IBD) is a chronic multifactorial inflammatory disorder characterized by periods of activation and remission of intestinal inflammation, with potentially severe complications, that can lead to mortality. Experimental animal models of intestinal inflammation are crucial for understanding the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), the two major human IBD phenotypes. Animal models have been instrumental in unveiling the molecular background of IBD, and although a single model is not able to capture the complexity of this disease, each of them provided valuable insight into its different aspects. Chemically induced models of intestinal inflammation, mainly dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, are widely used. This article describes DSS- and TNBS-induced colitis models and their relevance to IBD pathophysiology and pre-clinical therapeutic management. © 2017 by John Wiley & Sons, Inc.


Introduction of a Microsoft Excel-based unified electronic weekend handover document in Acute and General Medicine in a DGH: aims, outcomes and challenges.
On-call weekends in medicine can be a busy and stressful time for junior doctors, as they are responsible for a larger pool of patients, most of whom they would have never met. Clinical handover to the weekend team is extremely important and any communication errors may have a profound impact on patient care, potentially even resulting in avoidable harm or death. Several senior clinical bodies have issued guidelines on best practice in written and verbal handover. These include: standardisation, use of pro forma documents prompting doctors to document vital information (such as ceiling of care/resuscitation status) and prioritisation according to clinical urgency. These guidelines were not consistently followed in our hospital site at the onset of 2014 and junior doctors were becoming increasingly dissatisfied with the handover processes. An initial audit of handover documents used across the medical division on two separate weekends in January 2014, revealed high variability in compliance with documentation of key information. For example, ceiling of care was documented for only 14-42% of patients and resuscitation status in 26-72% of patients respectively. Additionally, each ward used their own self-designed pro forma and patients were not prioritised by clinical urgency. Within six months from the introduction of a standardised, hospital-wide weekend handover pro forma across the medical division and following initial improvements to its layout, ceiling of therapy and resuscitation status were documented in approximately 80% of patients (with some minor variability). Moreover, 100% of patients in acute medicine and 75% of those in general medicine were prioritised by clinical urgency and all wards used the same handover pro forma.


Assessment and treatment approaches for behavioral disturbances associated with dementia in the nursing home: self-reports of physicians' practices.
Behavior problems are common in dementia, yet little is known about how physicians deal with these problems in practice. This article reports on a survey asking physicians to describe, with respect to the last nursing home resident with dementia they treated for behavior problems, the behaviors observed, assessment methods used, suspected etiology of the problem, types of intervention, and their reaction to the intervention process. This is a descriptive study presenting responses to a Web-based questionnaire. Participants were 110 physicians providing services to nursing home residents. Physicians answered a close-ended questionnaire with open-ended "other" options concerning symptoms, methods of assessment, suspected etiological factors, and interventions to describe the last nursing home resident they treated for behavior problems associated with dementia. Resisting care was the most frequently reported symptom (71%). Physicians were most likely to attribute the behavior problems to the indirect effects of dementia on the ability to remember, communicate, and comprehend (67%). Most (87%) reported using more than one method for treating these problems. Rate of reported use of psychotropic drugs (80%) was slightly higher than that for nonpharmacological methods (75%), with the majority (61%) reporting use of both of these methods. Standardized instruments were not used in assessment. Forty percent of the participants reported feeling satisfied or very satisfied with the intervention they provided, and close to a third (32%) reported feeling frustrated with the intervention process. The data underscore the complexity in the treatment of behavior problems. Despite federal regulations limiting their use, the potential for side effects, and ambivalence toward such treatment, psychotropic drugs are still used for the majority of nursing home residents with behavior problems associated with dementia. On the other hand, physicians report employing nonpharmacological methods to a closely similar extent, although their role in the implementation of these treatments is less clear. Further work is needed to clarify physicians' involvement in and decision to use nonpharmacological interventions.


Pruritic Urticarial Papules and Plaques of Pregnancy Occurring Postpartum Treated with Intramuscular Injection of Autologous Whole Blood.
Pruritic urticarial papules and plaques of pregnancy (PUPPP) is one of the most common diseases associated with pregnancy. In most cases, the skin lesions develop in the third trimester of primigravidas. There are no systemic alterations seen in PUPPP; however, most patients report severe pruritus. A 34-year-old woman presented 1 week postpartum with typical clinical features of PUPPP. The patient showed good response to intramuscular injection of autologous whole blood with no adverse effects to the patient or her baby. Presentation of PUPPP in the postpartum period is rare. Conservative management with topical corticosteroids and oral antihistamines is commonly used to relieve pruritus. In severe cases, skin lesions and symptoms are controlled with a brief course of systemic corticosteroids. Investigation of new treatment options has been limited by patient concerns about the negative effects of medication on the fetus or breastfeeding. Intramuscular injection of autologous whole blood could be an alternative treatment option for PUPPP, especially for women who worry about the use of medications during pregnancy or breastfeeding.


Shared Decision-Making: Some cautionary observations in the context of elite sport.
The concept of shared decision-making (SDM) has emerged as a key component in the return to play interface as a hallmark of good practice that is athlete focused and allows greater engagement from the athlete. SDM is an appealing, well-intentioned framework that would seemingly lend itself to effectively being implemented. However, in this editorial, we have identified concerns surrounding the social complexities of elite sports and the difficulties of truly applying this concept in practice. In what follows, we explain the dynamics associated, discuss the importance of context when considering the efficacy of this practice and lastly offer what we see as certain key issues that might impede effective SDM.


Lymphocytotoxic cross-matching performed on spleen cells: immunomagnetic technique versus current KN (Kissmeyer-Nielsen) technique.
This paper compares the immunomagnetic (IM) and the KN lymphocytotoxic cross-matching techniques. Only sera from patients with panel reactive antibodies and spleen cells from cadaveric donors were used. A panel study involving 60 combinations revealed 11 (18%) discrepancies. Four T-cell cross-matches were KN negative while IM positive. Inversely, six T-cell cross-matches were IM negative while KN positive (two) or doubtfully positive (four). Regarding HLA class II antibodies, one combination was found IM positive but KN negative. Out of 106 cadaveric renal allograft transplantations performed during 1987 with assistance from our laboratory, IM cross-matching was retrospectively performed on 33 KN T-cell cross-match negative donor-recipient pairs: two combinations were found T-cell cross-match positive. The corresponding allografts were not lost owing to hyperacute rejection involving performed antibodies. We recommend the IM technique for HLA typing, but more experience needs to be gained before we can recommend the technique for routine cross-matching prior to transplantation.


The Impact of Community Generated PPE During the SARS-COV-2 Pandemic in Southeast Alabama and Gulfport Mississippi.
Background: The early stages of the SARS-COV-2 pandemic left many hospital systems devoid of personal protective equipment. Community-driven groups manufactured Personal Protective Equipment (PPE) as a form of temporary replacement until supply could increase to frontline healthcare workers. The purpose of this study was to survey hospital systems in Alabama and Mississippi who requested and received PPE to determine recipient opinions concerning community involvement. Methods: A 15-question Qualtrics survey was distributed to hospital systems who requested and received community-generated PPE (CGPPE) from the group known as Alabama Fighting COVID. 275 responses were gathered over a period of 6 months. Results: Survey data showed that most respondents from healthcare and healthcare-associated professions responded that wearing community generated personal protective equipment provided them with the perception of added protection (55.31% of participants selected either "Agree" or "Strongly Agree"), and that it improved their outlook and desire to work during the pandemic (51.77% of participants selected either "Agree" or "Strongly Agree"). Conclusions: Most respondents reported that wearing community generated personal protective equipment not only provided them with the perception of added protection, but that it improved their outlook and desire to work during the pandemic. With these responses in mind, our study raises questions concerning whether local CGPPE distribution could improve well-ness outcomes of healthcare workers (HCWs) not only in relation to decreased viral transmission, but also in favorable psychosocial health assessments. Further implications for research concerning community involvement during future medical crises are indicated, especially with the current rise of the delta variant strain.


Eradication of communicative disorders: preventive medicine in the 21st century.
Profound changes in our society occurring over the past few decades have resulted in a major shift in societal emphasis from labor to communication. The widespread use of personal computers has enhanced the importance of information-communication in daily life. People with communication disorders are at substantial risk of underemployment and lowered quality of life. Advances in medical science and hearing health care have placed us on the thresholds of being able to correct, rather than remediate, certain types of hearing loss. The finding that auditory hair cells of submammalian species regenerate has stimulated greatly the field of auditory research. A new lexicon is required to describe this emerging field. Methods exist to protect against hearing loss, repair affected structures prior to their degeneration, promote dedifferentiation-redifferentiation of undamaged structures into sensory cells, and, finally, promote regeneration of new sensory cells from precursor cells. Each of these processes has unique requirements, and all may be required to promote the restoration of hearing following damage or disease.


Education and training programs at the National Cancer Institute: 1938-1982.
The National Cancer Institute (NCI) has supported cancer research training and clinical cancer education since 1938, the latter in a variety of forms. These include direct clinical fellowships, followed by institutional grants designed to improve the education of students concerning cancer in medical and dental schools, and subsequently in teaching hospitals. The institutional grants went through three stages between 1948 and 1982, and have recently entered a fourth. Undergraduate Cancer Training Grants supported cancer teaching for medical and dental students. Clinical Cancer Training Grants expanded teaching activities to include post-resident trainees and medical and dental practitioners. Clinical Cancer Education Grants further extended cancer education and emphasized goals, objectives and evaluation, and focused on areas of weakness in cancer teaching such as epidemiology and cancer, cancer prevention and the role of radiation therapy. The various pressures within and without NCI that have influenced the development of these grant programs are discussed. Some cancer education activities supported by Cancer Control programs, both at NCI and another agency of the Public Health Service, are briefly mentioned. Aspects of the grant review process, program monitoring, and the impact of a professional organization developed in direct response to the first institutional cancer education grant program are described.


Piloting water quality testing coupled with a national socioeconomic survey in Yogyakarta province, Indonesia, towards tracking of Sustainable Development Goal 6.
There remains a pressing need for systematic water quality monitoring strategies to assess drinking water safety and to track progress towards the Sustainable Development Goals (SDG). This study incorporated water quality testing into an existing national socioeconomic survey in Yogyakarta province, Indonesia; the first such study in Indonesia in terms of SDG tracking. Multivariate regression analysis assessed the association between faecal and nitrate contamination and drinking water sources household drinking water adjusted for wealth, education level, type of water sources and type of sanitation facilities. The survey observed widespread faecal contamination in both sources for drinking water (89.2%, 95%CI: 86.9-91.5%; n=720) and household drinking water (67.1%, 95%CI: 64.1-70.1%; n=917) as measured by Escherichia coli. This was despite widespread improved drinking water source coverage (85.3%) and commonly self-reported boiling practices (82.2%). E.coli concentration levels in household drinking water were associated with wealth, education levels of a household head, and type of water source (i.e. vender water or local sources). Following the proposed SDG definition for Target 6.1 (water) and 6.2 (sanitation), the estimated proportion of households with access to safely managed drinking water and sanitation was 8.5% and 45.5%, respectively in the study areas, indicating substantial difference from improved drinking water (82.2%) and improved sanitation coverage (70.9%) as per the MDGs targets. The greatest contamination and risk factors were found in the poorest households indicating the urgent need for targeted and effective interventions here. There is suggested evidence that sub-surface leaching from on-site sanitation adversely impacts on drinking water sources, which underscores the need for further technical assistance in promoting latrine construction. Urgent action is still needed to strengthen systematic monitoring efforts towards tracking SDG Goal 6.


Two new species of Acontias (Acontinae, Scincidae) from the Mpumalanga Highveld escarpment of South Africa.
The African genus of fossorial legless lizards (Acontias Cuvier) currently comprises 26 species and subspecies. In a recent study on the two disjunct populations of Acontias breviceps Essex, the presence of cryptic species was discovered. Here, we increase the sampling size and describe these disjunct populations from the Mpumalanga Escarpment of South Africa as new species. The new species differ from congeners based on a combination of factors, including the number of midbody, ventral, and subcaudal scale counts, ventral pigmentation, allopatric distributions, and genetic divergences. The new species are genetically distant from nominal A. breviceps, with which it shares overall pigmentation and scalation. The new description adds to the growing number of Mpumalanga escarpment endemic reptiles, and highlights the area as a biodiversity hotspot. The use of vertebral counts as a distinguishing character between species is briefly discussed.


PERCEPTION AND UTILIZATION OF ORAL HISTOPATHOLOGY SERVICES BY GENERAL PRACTICE DENTIST IN SOUTHWEST NIGERIA.
Oral histopathology services are oral diagnostic procedures. General Dental Practitioners (GDPs) are routinely exposed to oral lesions that require biopsies. Hence, the study's objective of assessing the perception and the utilization of oral histopathology services by GDPs. This was a cross-sectional study conducted at dental clinics distributed across Southwest Nigeria. A self-administered questionnaire consisting of sections addressing the socio-demographic/professional aspects; the beliefs of GDPs and their utilization of oral histopathology services was used to collect data. A modified 5-point Likert rating scale was used to indicate the extent of agreement or disagreement with statement constructs. Analysis was done using SPSS for windows version 20.0. Significance was assessed at 5%. There were 56.1% males and 43.9% females. The peak age range was 30-39 years (35.4%), while 58.5% had ≤ 10 years of practice and 79.3% work in government dental centres. Many of the respondents (61.0%) thought suspicious lesions should be biopsied, 47.6% thought that specialists' skills were not required for biopsy. Furthermore, 53.7% had poor perception scores while 81.1% of those who had seen oral lesions that required biopsies, had poor utilization scores. The GDPs had a poor perception and utilization of oral histopathology services. Continuous medical education is needed to increase awareness amongst dentists.


Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study.
Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (pinteraction=0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. VeriStrat classification may guide treatment decisions in patients with SCC of the lung. ClinicalTrials.gov registration number: NCT01523587.


Respiratory Tract Infections and the Role of Biologically Active Polysaccharides in Their Management and Prevention.
Respiratory tract infections (RTIs) are the most common form of infections in every age category. Recurrent respiratory tract infections (RRTIs), a specific form of RTIs, represent a typical and common problem associated with early childhood, causing high indirect and direct costs on the healthcare system. They are usually the consequence of immature immunity in children and high exposure to various respiratory pathogens. Their rational management should aim at excluding other severe chronic diseases associated with increased morbidity (e.g., primary immunodeficiency syndromes, cystic fibrosis, and ciliary dyskinesia) and at supporting maturity of the mucosal immune system. However, RRTIs can also be observed in adults (e.g., during exhausting and stressful periods, chronic inflammatory diseases, secondary immunodeficiencies, or in elite athletes) and require greater attention. Biologically active polysaccharides (e.g., β-glucans) are one of the most studied natural immunomodulators with a pluripotent mode of action and biological activity. According to many studies, they possess immunomodulatory, anti-inflammatory, and anti-infectious activities and therefore could be suggested as an effective part of treating and preventing RTIs. Based on published studies, the application of β-glucans was proven as a possible therapeutic and preventive approach in managing and preventing recurrent respiratory tract infections in children (especially β-glucans from Pleurotus ostreatus), adults (mostly the studies with yeast-derived β-glucans), and in elite athletes (studies with β-glucans from Pleurotus ostreatus or yeast).


A highly efficient genetic system for the identification of a harzianum B biosynthetic gene cluster in Trichoderma hypoxylon.
Trichoderma hypoxylon is a fungicolous species which produces rich secondary metabolites. However, no genetic transformation method is available for further studies. Here, we developed a marker-less transformation system based on the complementation of an uridine/uracil biosynthetic gene by protoplast transformation. An uridine/uracil auxotrophic mutant of Δthpyr4 was obtained by using a positive screening protocol with 5'-fluoroorotic acid as a selective reagent. To improve the homologous integration rates, the orthologues of ku70 and lig4 which play critical roles in non-homologous end-joining recombination were disrupted. The resulting thlig4 mutant showed remarkable transformation rates of 89 %, while no change was found in the thku70 deletion mutant compared with the WT strain. This suggests that thlig4 play a key role in the non-homologous recombination in this strain. Using this system, the biosynthetic gene cluster of trichothecene (tri) harzianum B was identified by deletion of the thtri5 in T. hypoxylon. Comparative genome analysis revealed that the trichothecene biosynthetic gene cluster in T. hypoxylon shared similar organizations with T. arundinaceum and T. brevicompactum, even though their encoded products are different in structures. Taken together, the highly efficient genetic system provides a convenient tool for studying the biosynthetic diversity and mining the novel natural product from the fungi.


Home rehabilitation after hip fracture. A randomized controlled study on balance confidence, physical function and everyday activities.
To investigate whether home rehabilitation can improve balance confidence, physical function and daily activity level compared to conventional care in the early phase after hip fracture. A randomized controlled study. Geriatric rehabilitation clinic. One hundred and two community-dwelling elderly people. A geriatric, multiprofessional home rehabilitation programme focused on supported discharge, independence in daily activities, and enhancing physical activity and confidence in performing daily activities was compared with conventional care in which no structured rehabilitation after discharge was included. Falls efficacy, degree of dependency and frequency in daily activities, habitual physical activity and basic functional performance. When comparing status one month after discharge with baseline, the home rehabilitation group showed a higher degree of recovery in self-care (P<0.0001), mobility (P = 0.002), locomotion (P = 0.0036) and domestic activities (P = 0.0098), as well as larger increase in balance confidence on stairs (P = 0.0018) and instrumental activities (mean increase home rehabilitation 19.7 and conventional care 7.1, P<0.0001) compared with the conventional care group. At one month, a majority of the home rehabilitation participants (88%) took outdoor walks, compared with less than half (46%) of the conventional care group (P<0.001) and were also more independent in outdoor activities (P = 0.0014). This study indicates that home rehabilitation, focused on supported discharge and enhancing self-efficacy, improves balance confidence, independence and physical activity in community-dwelling older adults in the early phase after hip fracture.


Leptin signaling and the intervertebral disc: Sex dependent effects of leptin receptor deficiency and Western diet on the spine in a type 2 diabetes mouse model.
Type 2 diabetes and obesity are associated with back pain in juveniles and adults and are implicated in intervertebral disc (IVD) degeneration. Hypercaloric Western diets are associated with both obesity and type 2 diabetes. The objective of this study was to determine if obesity and type 2 diabetes result in spinal pathology in a sex-specific manner using in vivo diabetic and dietary mouse models. Leptin is an appetite-regulating hormone, and its deficiency leads to polyphagia, resulting in obesity and diabetes. Leptin is also associated with IVD degeneration, and increased expression of its receptor was identified in degenerated IVDs. We used young, leptin receptor deficient (Db/Db) mice to mimic the effect of diet and diabetes on adolescents. Db/Db and Control mice were fed either Western or Control diets, and were sacrificed at 3 months of age. Db/Db mice were obese, while only female mice developed diabetes. Female Db/Db mice displayed altered IVD morphology, with increased intradiscal notochordal band area, suggesting delayed IVD cell proliferation and differentiation, rather than IVD degeneration. Motion segments from Db/Db mice exhibited increased failure risk with decreased torsional failure strength. Db/Db mice also had inferior bone quality, which was most prominent in females. We conclude that obesity and diabetes due to impaired leptin signaling contribute to pathological changes in vertebrae, as well as an immature IVD phenotype, particularly of females, suggesting a sex-dependent role of leptin in the spine.


Neural Correlates of Psychotherapeutic Treatment of Post-traumatic Stress Disorder: A Systematic Literature Review.
Post-traumatic stress disorder (PTSD) is a common psychiatric disease with changes in neural circuitries. Neurobiological models conceptualize the symptoms of PTSD as correlates of a dysfunctional stress reaction to traumatic events. Functional imaging studies showed an increased amygdala and a decreased prefrontal cortex response in PTSD patients. As psychotherapeutic approaches represent the gold standard for PTSD treatment, it is important to examine its underlying neurobiological correlates. Studies published until August 2016 were selected through systematic literature research in the databases PubMed, PsychInfo, and Cochrane Library's Central Register of Controlled Trials or were identified manually by searching reference lists of selected articles. Search terms were "neural correlates" OR "fMRI" OR "SPECT," AND "therapy" AND "PTSD." A total of 19 articles were included in the present review whereof 15 studies compared pre-to-post-therapy signal changes, six studies related pre-treatment activity to pre-to-post-symptom improvement, and four studies compared neural correlates of responders versus non-responders. The disposed therapy forms were cognitive behavioral therapy (CBT), eye movement desensitization and reprocessing, cognitive therapy, exposure therapy, mindfulness-based intervention, brief eclectic psychotherapy, and unspecified therapy. Successful psychotherapy of PTSD was repeatedly shown to be accompanied by decreased activity in the amygdala and the insula as well as increased activity in the dorsal anterior cingulate cortex (dACC) and hippocampus. Elevated dACC activity prior to treatment was related to subsequent treatment success and a positive predictor for treatment response. Elevated amygdala and insula pre-treatment activities were related to treatment failure. Decreased activity in limbic brain regions and increased activity in frontal brain areas in PTSD patients after successful psychotherapeutic treatment might reflect regained top-down control over previously impaired bottom-up processes.


Low-anxiety rat phenotypes can be further reduced through genetic intervention.
A previous study using an intercross between the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) identified a locus on chromosome 4, named Anxrr16, influencing an experimental index of anxiety and showing a transgressive effect, with alleles from the LEW strain (more anxious) decreasing rather than increasing anxiety. To confirm the location and isolate the effect of a rat genome region named Anxrr16 through a planned genomic recombination strategy, where the target locus in SHR rats was replaced with LEW genetic material. A new congenic strain, named SHR.LEW-Anxrr16 (SLA16), was developed from a cross between LEW (donor) and SHR (receptor) rats and then evaluated in several anxiety-related tests. The activity and attention levels of the new strain were also evaluated, since hyperactivity was observed during its construction and because SHR is a model of attention deficit hyperactivity disorder. Significant effects of Anxrr16 were found for open field central locomotion, as well as for other indices of anxiety from the light/dark box, triple test and T-maze. In all cases, the low-anxiety levels of SHR rats were further reduced by the insertion of LEW alleles. Differences in locomotor activity were found only in unfamiliar (hence stressful) environments and no genetic effects were observed in indices of attention. The SLA16 strain can help in the identification of the molecular pathways involved in experimental anxiety and it demonstrates how apparently extreme phenotypes sometimes hide major opposite-acting genes.


MR findings of spinal muscular atrophy Type II: sibling cases.
We present magnetic resonance (MR) findings of siblings affected by spinal muscular atrophy (SMA) Type II. MRI of their thighs showed severe muscle atrophy and fatty infiltration. Selective preservation of the adductor longus muscle, the gracilis muscle, and the sartorius muscles was observed, suggesting a characteristic finding of SMA Type II. These findings were more severe in the older patient.


[Characteristics of urinary steroid excretions in ovarian cancer patients].
We performed a case-control study to investigate the urinary steroid excretions in ovarian cancer patients. The use of gas-liquid chromatography permitted the estimation of 14 urinary steroids. Data on 139 urine specimens from 36 cancer patients were compared with those on age-matched controls. A general depression of adreno-corticosteroid excretions was consistently observed in the cancer patients as compared with the control women. The possible role of observed steroidal disorders in the genesis of ovarian neoplasia is discussed in light of the epidemiological and biological aspects of this tumor.


Diffusion in the presence of cylindrical obstacles arranged in a square lattice analyzed with generalized Fick-Jacobs equation.
The generalized Fick-Jacobs equation is widely used to study diffusion of Brownian particles in three-dimensional tubes and quasi-two-dimensional channels of varying constraint geometry. We show how this equation can be applied to study the slowdown of unconstrained diffusion in the presence of obstacles. Specifically, we study diffusion of a point Brownian particle in the presence of identical cylindrical obstacles arranged in a square lattice. The focus is on the effective diffusion coefficient of the particle in the plane perpendicular to the cylinder axes, as a function of the cylinder radii. As radii vary from zero to one half of the lattice period, the effective diffusion coefficient decreases from its value in the obstacle free space to zero. Using different versions of the generalized Fick-Jacobs equation, we derive simple approximate formulas, which give the effective diffusion coefficient as a function of the cylinder radii, and compare their predictions with the values of the effective diffusion coefficient obtained from Brownian dynamics simulations. We find that both Reguera-Rubi and Kalinay-Percus versions of the generalized Fick-Jacobs equation lead to quite accurate predictions of the effective diffusion coefficient (with maximum relative errors below 4% and 7%, respectively) over the entire range of the cylinder radii from zero to one half of the lattice period.


Phylogeny of the Ophiostoma stenoceras-Sporothrix schenckii complex.
Ophiostoma stenoceras is a well-known sapwood-colonizing fungus occurring on some coniferous and hardwood hosts in the Northern Hemisphere. In the Southern Hemisphere, the fungus has been reported only from New Zealand. The human pathogen, Sporothrix schenckii, has been suggested to be the anamorph of O. stenoceras. The aim of this study was to gain a better understanding of the phylogenetic relationship between these two species. The study also provided the opportunity to confirm the identity of some Sporothrix and O. stenoceras-like isolates recently collected from wood and soil around the world. For this purpose, the DNA sequence of internal transcribed spacer (ITS) regions of the ribosomal RNA operon was determined. Isolates of O. nigrocarpum, O. albidum, O. abietinum, O. narcissi and O. ponderosae, all morphologically similar to O. stenoceras, were included in the study. From phylogenetic analyses of the sequence data, four main clades were observed. These represented O. stenoceras, O. nigrocarpum and two separate groups containing isolates of S. schenckii. Our results confirm earlier suggestions that S. schenckii should be classified within the teleomorph genus Ophiostoma but support studies separating O. stenoceras and S. schenckii. Ophiostoma albidum and O. ponderosae should be considered synonyms of O. stenoceras. The status of O. narcissi and O. abietinum needs further clarification. The two groups within S. schenckii might represent two species, but this needs to be confirmed. This study represents the first reports of O. stenoceras from Colombia, Kenya, Uruguay and South Africa.


Evolving strategies for optimal care management and plan benefit designs.
As a prevalent, complex disease, diabetes presents a challenge to managed care. Strategies to optimize type 2 diabetes care management and treatment outcomes have been evolving over the past several years. Novel economic incentive programs (eg, those outlined in the Patient Protection and Affordable Care Act of 2010 that tie revenue from Medicare Advantage plans to the quality of healthcare delivered) are being implemented, as are evidence-based interventions designed to optimize treatment, reduce clinical complications, and lower the total financial burden of the disease. Another step that can improve outcomes is to align managed care diabetes treatment algorithms with national treatment guidelines. In addition, designing the pharmacy benefit to emphasize the overall value of treatment and minimize out-of-pocket expenses for patients can be an effective approach to reducing prescription abandonment. The implementation of emerging models of care that encourage collaboration between providers, support lifestyle changes, and engage patients to become partners in their own treatment also appears to be effective.


Crystallization and preliminary X-ray diffraction analysis of phosphoglucose isomerase from Pyrococcus furiosus.
In several euryarchaeota, phosphoglucose isomerase (PGI) activity is catalyzed by an enzyme unrelated to the well-known family of PGI enzymes found in prokaryotes, eukaryotes and some archaea. In order to understand the mechanistic differences between the two families of enzymes we have crystallized PGI from the archaeon Pyrococcus furiosus. The crystals belong to the space group P2(1) and a complete dataset extending to 1.9 A resolution has been collected.


Ureteroarterial Fistula: A Diagnosis Which Is Not Always Black and White.
Ureteroiliac artery fistulas are a rare, life-threatening condition that requires a high index of suspicion for prompt diagnosis. Presurgical diagnosis is challenging as this condition can lie hidden despite advanced imaging modalities. We present two cases of patients presenting with gross hematuria and exsanguination in the setting of a ureteroiliac artery fistula. These cases highlight the difficulties in timely diagnosis and treatment in a multidisciplinary team.


Sonophotocatalytic water splitting by BaTiO3@SrTiO3 core shell nanowires.
Sonophotocatalysis has garnered significant attention due to its potential to enhance advanced oxidation processes, particularly water splitting, by employing materials with combined sonocatalytic and photocatalytic properties. In this study, we synthesized and investigated core-shell BaTiO3@SrTiO3 nanowires (BST NWs) with varying Sr/Ba molar ratios (2.5:7.5, 5.0:5.0, 7.5:2.5 mM, denoted as BST-1, BST-2, and BST-3, respectively) as catalysts for hydrogen production through water splitting. The piezoelectric nanowires demonstrated hydrogen evolution via both sonocatalysis and photocatalysis. In the sonophotocatalysis process, the ultrasonic vibration induced mechanical forces on the BST nanowires, thereby establishing a built-in electric field. This built-in electric field facilitated the effective separation of photo-generated charge carriers and prolonged their lifetimes, leading to a synergistic enhancement of hydrogen evolution. The pristine BaTiO3 and SrTiO3 nanowires exhibited relatively low hydrogen evolution rates (HER) of 7.0 and 6.0 µmol·g-1min-1, respectively. In contrast, the core-shell nanowires exhibited a substantial improvement in the hydrogen evolution rate. The HER increased with the addition of Sr, and BST-1, BST-2, and BST-3 achieved HERs of 12.0, 13.5, and 18.0 µmol·g-1min-1, respectively. The superior performance of BST-3 nanowires can be attributed to their highest piezoelectric potential and largest surface area. Additionally, BST-3 nanowires demonstrated remarkable stability over multiple cycles, validating their practical applicability as efficient photocatalysts.


19 F NMR Spectroscopic Analysis of the Binding Modes in Triple-Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes.
Triplex-forming peptide nucleic acids (TFPNAs) were targeted to double-helical regions of 19 F-labeled RNA hairpin models (a UA-rich duplex with a hexaethylene glycol (heg) loop and a microRNA model, miR-215). In addition to conventional UV- and circular dichroism (CD)-based detection, binding was monitored by 19 F NMR spectroscopy. Detailed information on the stoichiometry and transition between the triple-helical peptide nucleic acid (PNA)/RNA and (PNA)2 /RNA binding modes could be obtained. γ-(R)-Hydroxymethyl-modified thymine-1-yl- and 2-aminopyridin-3-yl-acetyl derivatives of TFPNAs were additionally synthesized, which were targeted to the same RNA models, and the effect of the γ-(R)-hydroxymethyl group on binding was studied. An appropriate pattern of γ-(R)-hydroxymethyl modifications reduced the stability of the ternary complex and preferred stoichiometric binding to the miR-215 model.


Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer.
Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response. We applied tumor cell lysate plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally (n=8) as a cancer vaccine to patients suffering from advanced solid pediatric malignancies. No serious adverse events were observed following application of IL-12-releasing smDC. Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test. We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.


Dissociation of 2,4-bis(2,4,6-tri-tert-butylphenyl)-cyclo-1,3-dipnicta-2,4-diazanes (pnict = P, As, Sb) imposed by substituent steric strain: a cyclobutane/olefin analogy.
Three 2,4-bis(Mes)-cyclo-1,3-dipnicta-2,4-diazanes, 2PnX, have been synthesized as 1,3-dichloro- (Pn = As; X = Cl) or 1,3-bis(triflato)- (Pn = P, Sb; X = OTf) derivatives (Mes = 2,4,6-tri-tert-butylphenyl; OTf = triflato = trifluoromethanesulfonoxy). The compounds have been structurally characterized as cyclodimers, but spectroscopic characterization of melts and solutions indicates facile dissociation of the diphosphadiazane 2POTf derivative to give the corresponding iminophosphine 1POTf and of the diarsadiazane 2AsCl derivative to give the corresponding iminoarsine 1AsCl. 1,3-Bis(triflato)-2,4-bis(Mes)-cyclo-1,3-distiba-2,4-diazane (2SbOTf) does not dissociate in the melt or in solution. The presence of the sterically bulky Mes substituent does not preclude association of N-Pn olefin analogues to give single bonded cyclobutane analogues. The facile dissociation of 2POTf and isolation of 1POTf implicates a relatively high degree of substituent steric strain in the dimer. In comparison, dissociation of 2AsCl is only apparent in the melt and in solution, likely the result of the lower substituent strain in the larger N(2)As(2) framework. The largest N(2)Pn(2) framework in 2SbOTf provides sufficient space for the Mes substituents, and the monomer is not observed under the conditions examined.


[Anesthesia management in robotic-assisted esophagectomy with triple incisions: analysis of 53 cases].
Between March, 2016 and January, 2017, 53 patients underwent robotic-assisted esophagectomy with triple incisions. All the patients were intubated with Double lumen endotracheal tub with one-lung ventilation and CO2 pneumoperitoneum, and CO2 pneumothorax was used in 7 cases. Most of the patients could tolerate OLV and CO2 pneumoperitoneum, and 4 patients with CO2 pneumothorax had hypoxemia and required double-lung ventilation or high frequency ventilation; 15 patients developed postoperative pulmonary complications and were transferred to ICU. These results suggest that CO2 pneumothorax during robotic-assisted esophagectomy with triple incision seriously disturbs pulmonary function, and careful anesthesia management is essential for preventing complications.


[Experience of an adherence support for HIV-1 seropositive patients with failure under treatment].
To be successful highly active antiretroviral therapies need very high levels of adherence to be successful. In need to help patients in dealing with adverse effects, complexity and multiple constraints of these drugs, adherence support programs have been developed. Therefore, the efficacy on viral load of these interventions has not been established in the HIV-1 positive population. The aim of our study was to assess the virological efficacy of this type of program in our institution. Non randomized intervention study with a control group. The intervention group was constituted of patients presenting with virological failure who where admitted in the adherence program. The control group (2:1) has been selected in our data base. Factors known to influence viral load have been analyzed by multiple logistic regression. The probability of obtaining a significant decrease of viral load was better at 6 months for patients using the adherence program (OR: 4,48 [2,72-11,8]). This benefit was not sustained at 12 months. The program efficacy varied with the kind of treatment (with or without protease inhibitors), the therapeutic history and the initial viral load. The absence of protease inhibitor, a high initial viral load, small number of previous drugs were linked to viral load decrease. The good virological results observed at 6 months in the intervention group are incentive. Long term virological gain and the profile of patients who could make the best of an adherence support program have to be determined.


Kalman estimator- and general linear model-based on-line brain activation mapping by near-infrared spectroscopy.
Near-infrared spectroscopy (NIRS) is a non-invasive neuroimaging technique that recently has been developed to measure the changes of cerebral blood oxygenation associated with brain activities. To date, for functional brain mapping applications, there is no standard on-line method for analysing NIRS data. In this paper, a novel on-line NIRS data analysis framework taking advantages of both the general linear model (GLM) and the Kalman estimator is devised. The Kalman estimator is used to update the GLM coefficients recursively, and one critical coefficient regarding brain activities is then passed to a t-statistical test. The t-statistical test result is used to update a topographic brain activation map. Meanwhile, a set of high-pass filters is plugged into the GLM to prevent very low-frequency noises, and an autoregressive (AR) model is used to prevent the temporal correlation caused by physiological noises in NIRS time series. A set of data recorded in finger tapping experiments is studied using the proposed framework. The obtained results suggest that the method can effectively track the task related brain activation areas, and prevent the noise distortion in the estimation while the experiment is running. Thereby, the potential of the proposed method for real-time NIRS-based brain imaging was demonstrated. This paper presents a novel on-line approach for analysing NIRS data for functional brain mapping applications. This approach demonstrates the potential of a real-time-updating topographic brain activation map.


POLLEN DISPERSAL DYNAMICS IN AN ALPINE WILDFLOWER, POLEMONIUM VISCOSUM.
The alpine wildflower, Polemonium viscosum, depends on insect visitors for effective pollination. Here, I examine experimentally the effects of pollinator visitation on pollen removal, pollen dispersal success, paternity, and gene flow. Bumble bee pollinators visited donor individuals homozygous for marker alleles at an isozyme (GOT-2) encoding locus and then were presented with arrays of recipient plants lacking the marker alleles. Four aspects of male fitness were estimated for each donor: the number of pollen grains dispersed to flowers of the first recipient visited, the number of offspring sired on that recipient, the proportion of offspring sired in the full array, and the proportion of mates in the array bearing seeds of the donor. Pollen removal was strongly influenced by the number of bee visits to donor flowers. The amount of pollen removed in turn significantly affected the number of pollen grains reaching flowers of the first recipient. However, because seed production decelerates with stigma pollen load, the relationship between pollen export and paternal success at this proximate scale showed diminishing returns. The probability of reaching mates within the array also increased with pollen export. These findings show that floral characters enhancing pollinator visitation rate in P. viscosum have positive effects on paternity and gene flow.


Active optical zoom system.
In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.


Forum-Pre-Sabine room acoustic assumptions on reverberation and their influence on room acoustic design.
With his work on the Fogg Art Museum and Boston Symphony Hall between 1895 and 1900, Wallace C. Sabine laid a foundation for the field of architectural acoustics as a science. Prior to that, architects employed various quantifiable notions in acoustic design. Previous studies have reviewed metric guidelines based on the directivity of the human voice, which was utilized in at least 11 rooms in pre-Sabine times. Others studies have reviewed pre-Sabine design guidelines that were based on the quantification of the perception threshold between direct sound and first order reflections and which were followed in several rooms with acoustical performance needs. As the first studies concerned the direct sound and the second set concerned first order reflections, this study reviews opinions and knowledge regarding the later part of the acoustic response, also known as reverberation, during the 19th century. This effort brings to light a room acoustic design evolution showing why concert halls at the end of the 19th century mainly had surface finishes of wood and plaster as well as limited ceiling heights. While not equal to Sabine's thoroughness and completeness, numerous early experimental and theoretical reverberation approaches were found to hint at similar notions with both qualitative and quantitative efforts.


Combination of therapeutic hypothermia and other neuroprotective strategies after an ischemic cerebral insult.
Abrupt deprivation of substrates to neuronal tissue triggers a number of pathological events (the "ischemic cascade") that lead to cell death. As this is a process of delayed neuronal cell death and not an instantaneous event, several pharmacological and non-pharmacological strategies have been developed to attenuate or block this cascade. The most promising neuroprotectant so far is therapeutic hypothermia and its beneficial effects have inspired researchers to further improve its protective benefit by combining it with other neuroprotective agents. This review provides an overview of all neuroprotective strategies that have been combined with therapeutic hypothermia in rodent models of focal cerebral ischemia. A distinction is made between drugs interrupting only one event of the ischemic cascade from those mitigating different pathways and having multimodal effects. Also the combination of therapeutic hypothermia with hemicraniectomy, gene therapy and protein therapy is briefly discussed. Furthermore, those combinations that have been studied in a clinical setting are also reviewed.


Role of Autophagy in Renal Cancer.
Autophagy is a highly conserved catabolic process with critical functions in maintenance of cellular homeostasis under normal growth conditions and in preservation of cell viability under stress. The role of autophagy in cancer is dual-sided. Autophagy-deficient cells are often more tumorigenic than their wild type counterparts in association with DNA damage accumulation, oxidative stress. At the same time, autophagy is a major cell survival mechanism. In recent years, it has been well demonstrated that autophagy may have relation with renal cell carcinoma (RCC). This review focuses on the research progress in relation between autophagy and RCC and the pharmacologic manipulation of autophagy for RCC treatment.


Survey of Current Practices: Peripheral Nerve Block Utilization by ED Physicians for Treatment of Pain in the Hip Fracture Patient Population.
In 2010-11 approximately 968 hip fracture patients presented to emergency departments in the Greater Toronto Local Health Integration Network (GTA-LHIN). Optimal pain management is a frequently overlooked aspect of hip fracture patient care, which may contribute to patient outcomes. Although recommendations have been published, there is currently not a standardized approach to the analgesic management of pain in the hip fracture patient. Nerve blocks, including the fascia iliaca compartment block (FICB), are more effective than traditional opioid analgesics in reducing pain after hip fracture. Research suggests that analgesia via nerve blockade is best initiated early, upon arrival to the emergency department. Emergency physicians are trained in ultrasound, and do utilize regional anaesthesia; however, the frequency of block utilization and techniques used for block insertion are unknown. We sought to undertake the first survey of Emergency Department (ED) staff and resident physicians across the GTA-LHIN, looking at the current ED practice of nerve block analgesia in hip fracture patients. The primary aim was to determine the prevalence and range of techniques utilized. The secondary aims were to determine the extent of training in nerve block insertion techniques, to gauge opinion on the most important objectives for future training courses, and to seek an understanding of the barriers to establishing a standardized approach for nerve block utilization in hip fracture patients. This data will be used to develop a multidisciplinary training program specifically for use by ED physicians. ED physicians and anesthesiologists will collaborate to standardize nerve block insertion techniques and develop an optimal analgesic management plan of hip fracture patients at Sunnybrook Hospital.


Development of the cat-owner relationship scale (CORS).
Characteristics of the human-animal bond can be influenced by both owner-related and pet-related factors, which likely differ between species. Three studies adapted the Monash Dog-Owner Relationship Scale (MDORS) to permit assessment of human-cat interactions as perceived by the cat's owner. In Study 1293 female cat owners completed a modified version of the MDORS, where 'dog' was replaced with 'cat' for all items. Responses were compared with a matched sample of female dog owners. A partial least squares discriminant analysis revealed systematic differences between cat and dog owners in the Dog (Cat)-Owner Interaction subscale (MDORS subscale 1), but not for Perceived Emotional Closeness or Perceived Costs (Subscales 2 and 3). Study 2 involved analysis of free-text descriptions of cat-owner interactions provided by 61 female cat owners. Text mining identified key words which were used to create additional questions for a new Cat-Owner Interaction subscale. In Study 3, the resulting cat-owner relationship scale (CORS) was tested in a group of 570 cat owners. The main psychometric properties of the scale, including internal consistency and factor structure, were evaluated. We propose that this scale can be used to accurately assess owner perceptions of their relationship with their cat. A modified scale, combining items from the CORS and MDORS (a C/DORS), is also provided for when researchers would find it desirable to compare human-cat and human-dog interactions.


[The Freud-Ferenczi relationship studied in the light of their correspondence].
The Freud-Ferenczi relationship was a more complex one than it is commonly thought to have been in psychoanalytic circles. It started in a less idyllic manner than it is said to have done, and it did not end in the breaking off of their relationship as many believe it did. Nonetheless, the two men were possessed of very dissimilar temperaments: the nature of the demands they made on each other were complementary, but impossible to satisfy. This situation led to a number of cases of friction which appeared in association with several major events, but evidence of these conflicts is also to be found in a number of small signs that can be detected throughout the correspondence between the two men. Despite the great complexity of emotions at play in their relationship, it resulted in a strong and loyal friendship that withstood the most directly expressed differences in opinion.