Health care utilisation and costs associated with different treatment protocols for newly diagnosed childhood acute lymphoblastic leukaemia: A population-based study in Ontario, Canada.
Although different treatment protocols for childhood acute lymphoblastic leukaemia (ALL) all achieve high cure rates, their health care utilisation and costs have not been rigorously compared. Disease, treatment, and outcome data were chart abstracted for all children with ALL in Ontario, Canada, diagnosed 2002-2012. Linkage to population-based databases identified health care utilisation. Utilisation-associated costs were determined through validated algorithms. Chemotherapy-associated costs were calculated separately. Health care utilisation and costs were compared between patients receiving Children's Oncology Group (COG) versus Dana-Farber Cancer Institute (DFCI)-based treatment. Of 802 patients, 146 (18.2%) were treated on DFCI-based protocols. COG patients experienced significantly higher rates of emergency department (ED) visits (adjusted rate ratio [aRR]: 1.3, 95% confidence interval [CI]: 1.1-1.5; p = 0·01), whereas outpatient visit rates were 60% higher among DFCI patients (aRR: 1.6, 95% CI: 1.5-1.7, p < 0.0001). In adjusted analyses, DFCI-associated cost intensity was 70% higher (aRR: 1.7, 95% CI: 1.5-1.9; p < 0.0001), mainly attributable to outpatient visit costs. Total chemotherapy costs were higher among COG-treated patients ($39,400 ± $1100 versus $33,400 ± $2800; p = 0.02). Among PEG-ASNase-treated patients, total chemotherapy costs were highest among DFCI patients (median $54,200 ± $7400; p = 0.003 versus COG patients). COG and DFCI treatments were associated with higher ED visit rates and higher outpatient visit rates, respectively. Overall utilisation-associated costs were increased in DFCI-treated patients. Administration of some intravenous chemotherapy at home and decreases in PEG-ASNase cost would decrease health care utilisation and costs for all patients and mitigate differences between COG and DFCI protocols. C17 Research Network.


Effectiveness of the delivery of interventions to prevent malaria in pregnancy in Kenya.
Coverage with malaria in pregnancy interventions remains unacceptably low. Implementation research is needed to identify and quantify the bottlenecks for the delivery and use of these life-saving interventions through antenatal clinics (ANC). A cross-sectional study was carried out in ANC across nine health facilities in western Kenya. Data were collected for an individual ANC visit through structured observations and exit interviews with the same ANC clients. The cumulative and intermediate systems effectiveness for the delivery of intermittent preventive treatment (IPTp) and insecticide-treated nets (ITNs) to eligible pregnant women on this one specific visit to ANC were estimated. Overall the ANC systems effectiveness for delivering malaria in pregnancy interventions was suboptimal. Only 40 and 53 % of eligible women received IPTp by directly observed therapy as per policy in hospitals and health centres/dispensaries respectively. The overall systems effectiveness for the receipt of IPTp disregarding directly observed therapy was 62 and 72 % for hospitals and lower level health facilities, respectively. The overall systems effectiveness for ITNs for first ANC visit was 63 and 67 % for hospitals and lower level facilities, respectively. This study found that delivery of IPTp and ITNs through ANC was ineffective and more so for higher-level facilities. This illustrates missed opportunities and provider level bottlenecks to the scale up and use of interventions to control malaria in pregnancy delivered through ANC. The high level of clustering within health facilities suggest that future studies should assess the feasibility of implementing interventions to improve systems effectiveness tailored to the health facility level.


Astroglial Connexins as a Therapeutic Target for Alzheimer's Disease.
In Alzheimer's disease (AD), modification of astrocytic properties is a well-known and documented fact, but their involvement in pathophysiology has only been examined in recent years. One distinct hallmark of AD is reactive gliosis which are represented in microglial and astrocytic phenotype changes. This reactive gliosis has been associated with changes in the expression and function of connexins. Connexins are proteins that can form gap junction channels and hemichannels, and in a disease context, have shown increased expression in astrocytes that contact amyloid plaques in vivo. Amyloid plaques are aggregates of the amyloid-beta protein, which present in the AD brain in patients and in animal models. Murine AD models demonstrate changes in connexin channel activity which mirror in cell culture systems treated with amyloid-beta peptide. This has been closely studied in the familial AD mouse model APPSwe/ PS1dE9 where the implications of connexin channel functions have been examined. These studies demonstrate that while gap junctional communication was unaffected, hemichannel activation could be detected in the astrocytes of hippocampal slices containing amyloid-beta plaques. Most critically, the activation of hemichannels is associated with the release of gliotransmitters (such as ATP and glutamate) which results in the maintenance of a high intracellular free Ca2+ concentration within astrocytes, which initiates the start of a vicious cycle. Strategies that target astroglial connexin hemichannels include the knocking out of the connexin 43 gene in astrocytes of the APPSwe/PS1dE9 mice, as well as using various pharmacological tools. This results in the decrease of gliotransmitter release and the alleviation of neuronal damage. This includes the reduction of oxidative stress and neuritic dystrophies in neurons that are typically associated with plaque formation in the hippocampus. Concusion: In this review, we summarize recent findings on astroglial connexin channels in the neurodegenerative process of Alzheimer's disease, and discuss how this can be a strategy in AD treatment to block the activity of hemichannels in astrocytes.


A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.
Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.


[Actovegin treatment of duodenal ulcer associated with ischemic heart disease and diabetes mellitus].
Actovegin, a deproteinized hemoderivative, was used to correct bioenergetic defects of duodenal mucosa, to reduce inflammatory-cell infiltration, to stimulate blood supply of patients with duodenal ulcer associated with ischemic heart disease or diabetes mellitus. As shown by the results obtained in 194 patients (119 males and 75 females), adjuvant actovegin in patients with duodenal ulcer associated with ischemic heart disease and diabetes mellitus stimulates the ulcer healing, prolongs the recurrence-free interval. It can be used both in outpatient departments and specialized hospitals.


[Chronic heart failure and cachexia: role of endocrine system].
Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.


Fetal circulation in left-sided congenital heart disease measured by cardiovascular magnetic resonance: a case-control study.
The distribution of blood flow in fetuses with congenital heart disease (CHD) is likely to influence fetal growth, organ development, and postnatal outcome, but has previously been difficult to study. We present the first measurements of the distribution of the fetal circulation in left-sided CHD made using phase contrast cardiac magnetic resonance (CMR). Twenty-two fetuses with suspected left-sided CHD and twelve normal controls underwent fetal CMR and echocardiography at a mean of 35 weeks gestation (range 30-39 weeks). Fetuses with left-sided CHD had a mean combined ventricular output 19% lower than normal controls (p < 0.01). In fetuses with left-sided CHD with pulmonary venous obstruction, pulmonary blood flow was significantly lower than in those with left-sided CHD without pulmonary venous obstruction (p < 0.01). All three fetuses with pulmonary venous obstruction had pulmonary lymphangectasia by fetal CMR and postnatal histology. Fetuses with small but apex forming left ventricles with left ventricular outflow tract or aortic arch obstruction had reduced ascending aortic and foramen ovale flow compared with normals (p < 0.01). Fetuses with left-sided CHD had more variable superior vena caval flows than normal controls (p < 0.05). Six fetuses with CHD had brain weights at or below the 5th centile for gestational age, while none of the fetuses in the normal control group had brain weights below the 25th centile. Measurement of the distribution of the fetal circulation in late gestation left-sided CHD is feasible with CMR. We demonstrated links between fetal blood flow distribution and postnatal course, and examined the relationship between fetal hemodynamics and lung and brain development. CMR enhances our understanding of pathophysiology of the fetal circulation and, with more experience, may help with the planning of perinatal management and fetal counselling.


Effect of body mass index on surgical outcomes after posterior spinal fusion for adolescent idiopathic scoliosis.
OBJECTIVE Obesity is an increasing public health concern in the pediatric population. The purpose of this investigation was to examine the impact of body mass index (BMI) on 30-day outcomes after posterior spinal fusion for adolescent idiopathic scoliosis (AIS). METHODS The American College of Surgeons National Surgical Quality Improvement Program Pediatric database (2013 and 2014) was reviewed. Patients 10-18 years of age who had undergone fusion of 7 or more spinal levels for AIS were included. Thirty-day outcomes (complications, readmissions, and reoperations) were compared based on patient BMI per age- and sex-adjusted growth charts as follows: normal weight (NW; BMI < 85th percentile), overweight (OW; BMI 85th-95th percentile), and obese (OB; BMI > 95th percentile). RESULTS Patients eligible for study numbered 2712 (80.1% female and 19.9% male) and had a mean age of 14.4 ± 1.8 years. Average BMI for the entire cohort was 21.9 ± 5.0 kg/m2; 2010 patients (74.1%) were classified as NW, 345 (12.7%) as OW, and 357 (13.2%) as OB. The overall complication rate was 1.3% (36/2712). For NW and OW patients, the complication rate was 0.9% in each group; for OB patients, the rate was 4.2% (p < 0.001). The 30-day readmission rate was 2.0% (55/2712) for all patients, 1.6% for NW patients, 1.2% for OW patients, and 5.0% for OB patients (p < 0.001). The 30-day reoperation rate was 1.4% (39/2712). Based on BMI, this reoperation rate corresponded to 0.9%, 1.2%, and 4.8% for NW, OW, and OB patients, respectively (p < 0.001). After controlling for patient age, number of spinal levels fused, and operative/anesthesia time on multiple logistic regression analysis, obesity remained a significant risk factor for complications (OR 4.61), readmissions (OR 3.16), and reoperations (OR 5.33; all p < 0.001). CONCLUSIONS Body mass index may be significantly associated with short-term outcomes after long-segment fusion procedures for AIS. Although NW and OW patients may have similar 30-day outcomes, OB patients had significantly higher wound complication, readmission, and reoperation rates and longer hospital stays than the NW patients. The findings of this study may help spine surgeons and patients in terms of preoperative risk stratification and perioperative expectations.


Quinine for muscle cramps.
Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. To assess the efficacy and safety of quinine in treating muscle cramps. We searched The Cochrane Neuromuscular Disease Group Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), MEDLINE, EMBASE and reference lists of articles up to July 2010. Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives. Three authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n =1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg).Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference +3%, 95% confidence intervals 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (risk difference 0%, 95% confidence intervals -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events. There is moderate quality evidence that quinine significantly reduces cramp frequency, intensity and cramp days in dosages between 200 and 500 mg/day. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials. Further research is required on the optimal dose and duration of use, and also on alternative treatments.


Imaging the physiological evolution of the ischemic penumbra in acute ischemic stroke.
We review the hemodynamic, metabolic and cellular parameters affected during early ischemia and their changes as a function of approximate cerebral blood flow ( CBF) thresholds. These parameters underlie the current practical definition of an ischemic penumbra, namely metabolically affected but still viable brain tissue. Such tissue is at risk of infarction under continuing conditions of reduced CBF, but can be rescued through timely intervention. This definition will be useful in clinical diagnosis only if imaging techniques exist that can rapidly, and with sufficient accuracy, visualize the existence of a mismatch between such a metabolically affected area and regions that have suffered cell depolarization. Unfortunately, clinical data show that defining the outer boundary of the penumbra based solely on perfusion-related thresholds may not be sufficiently accurate. Also, thresholds for CBF and cerebral blood volume ( CBV) differ for white and gray matter and evolve with time for both inner and outer penumbral boundaries. As such, practical penumbral imaging would involve parameters in which the physiology is immediately displayed in a manner independent of baseline CBF or CBF threshold, namely pH, oxygen extraction fraction ( OEF), diffusion constant and mean transit time ( MTT). Suitable imaging technologies will need to meet this requirement in a 10-20 min exam.


Diagnostic accuracy of 64-slice multislice computed tomographic coronary angiography in patients with an intermediate pretest likelihood for coronary artery disease.
Data on the diagnostic accuracy of multislice computed tomographic coronary angiography (CTA) have been mostly derived from patients with a high pretest likelihood of coronary artery disease. Systematic comparisons with invasive angiography in patients with an intermediate pretest likelihood are scarce. The purpose of the present study was to determine the diagnostic accuracy of CTA in patients without known coronary artery disease with an intermediate pretest likelihood. A total of 61 patients (61% men, average age 57 + or - 9 years) who had been referred for invasive coronary angiography underwent additional 64-slice CTA. A total of 920 segments were identified by invasive coronary angiography, of which 885 (96%) were interpretable on CTA. Invasive coronary angiography identified a significant stenosis (> or = 50% luminal narrowing) in 29 segments, of which 23 were detected on CTA. Thus, the sensitivity, specificity, positive predictive value, and negative predictive value was 79%, 98%, 61%, and 99%, respectively, for CTA. On a patient level, the sensitivity, specificity, positive predictive value, and negative predictive value was 100%, 89%, 76%, and 100%, respectively. CTA correctly ruled out the presence of significant stenosis in 40 (66%) of the 61 patients. In conclusion, the results from the present study have confirmed that CTA has excellent diagnostic accuracy in the target population of patients with an intermediate pretest likelihood. The high negative predictive value allowed us to rule out significant stenosis in a large proportion of patients. CTA can, therefore, be used as a highly effective gatekeeper for invasive coronary angiography.


Methods for determining stability in continuum elastic-rod models of DNA.
Elastic-rod models of DNA have offered an alternative method for studying the macroscopic properties of the molecule. An essential component of the modelling effort is to identify the biologically accessible, or stable, solutions. The underlying variational structure of the elastic-rod model can be exploited to derive methods that identify stable equilibrium configurations. We present two methods for determining the stability of the equilibria of elastic-rod models: the conjugate-point method and the distinguished-diagram method. Additionally, we apply these methods to two intrinsically curved DNA molecules: a DNA filament with an A-tract bend and a DNA minicircle with a catabolite gene activator protein binding site. The stable solutions of these models provide visual insight into the three-dimensional structure of the DNA molecules.


A direct comparison of central tendency recall and temporal integration in the successive field iconic memory task.
The ensemble coding literature suggests the existence of a fast, automatic formation of some ensemble codes. Can statistical representations, such as memory for the central tendency along a particular visual feature dimension, be extracted from information held in the sensory register? Furthermore, can knowledge of early, iconic memory processes be used to determine how central tendency is extracted? We focused on the potential role of visible persistence mechanisms that support temporal integration. We tested whether mean orientation could be accurately recalled from brief visual displays using the successive field task. On separate blocks of trials, participants were asked to report the location of a split element (requiring differentiation of frames), a missing element (requiring integration across frames), and the average orientation of elements pooled across both frames (central tendency recall). Results replicate the expected tradeoff between differentiation and integration performance across inter-frame interval (IFI). In contrast, precision of mean estimates was high and invariant across IFIs. A manipulation of within-frame distributional similarity coupled with simulations using 12 models supported 2-item subsampling. The results argue against the "strategic" interpretation of subsampling since 2-item readout was predicted by information theoretic estimates of STM encoding rate: the 2 items were not from a superset in STM. Most crucially, the results argue against the various early "preattentive/parallel/global pooling" accounts and instead suggest that non-selective readout of information from iconic memory supplies a relatively small amount of item information to STM, and it is only at this point that the computation of ensemble averages begins.


HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis.
Hepatic de-differentiation, liver development, and malignant transformation are processes in which the levels of hepatic S-adenosylmethionine are tightly regulated by 2 genes: methionine adenosyltransferase 1A (MAT1A) and methionine adenosyltransferase 2A (MAT2A). MAT1A is expressed in the adult liver, whereas MAT2A expression primarily is extrahepatic and is associated strongly with liver proliferation. The mechanisms that regulate these expression patterns are not completely understood. In silico analysis of the 3' untranslated region of MAT1A and MAT2A revealed putative binding sites for the RNA-binding proteins AU-rich RNA binding factor 1 (AUF1) and HuR, respectively. We investigated the posttranscriptional regulation of MAT1A and MAT2A by AUF1, HuR, and methyl-HuR in the aforementioned biological processes. During hepatic de-differentiation, the switch between MAT1A and MAT2A coincided with an increase in HuR and AUF1 expression. S-adenosylmethionine treatment altered this homeostasis by shifting the balance of AUF1 and methyl-HuR/HuR, which was identified as an inhibitor of MAT2A messenger RNA (mRNA) stability. We also observed a similar temporal distribution and a functional link between HuR, methyl-HuR, AUF1, and MAT1A and MAT2A during fetal liver development. Immunofluorescent analysis revealed increased levels of HuR and AUF1, and a decrease in methyl-HuR levels in human livers with hepatocellular carcinoma (HCC). Our data strongly support a role for AUF1 and HuR/methyl-HuR in liver de-differentiation, development, and human HCC progression through the posttranslational regulation of MAT1A and MAT2A mRNAs.


Theory of nanoparticle diffusion in unentangled and entangled polymer melts.
We propose a statistical dynamical theory for the violation of the hydrodynamic Stokes-Einstein (SE) diffusion law for a spherical nanoparticle in entangled and unentangled polymer melts based on a combination of mode coupling, Brownian motion, and polymer physics ideas. The non-hydrodynamic friction coefficient is related to microscopic equilibrium structure and the length-scale-dependent polymer melt collective density fluctuation relaxation time. When local packing correlations are neglected, analytic scaling laws (with numerical prefactors) in various regimes are derived for the non-hydrodynamic diffusivity as a function of particle size, polymer radius-of-gyration, tube diameter, degree of entanglement, melt density, and temperature. Entanglement effects are the origin of large SE violations (orders of magnitude mobility enhancement) which smoothly increase as the ratio of particle radius to tube diameter decreases. Various crossover conditions for the recovery of the SE law are derived, which are qualitatively distinct for unentangled and entangled melts. The dynamical influence of packing correlations due to both repulsive and interfacial attractive forces is investigated. A central finding is that melt packing fraction, temperature, and interfacial attraction strength all influence the SE violation in qualitatively different directions depending on whether the polymers are entangled or not. Entangled systems exhibit seemingly anomalous trends as a function of these variables as a consequence of the non-diffusive nature of collective density fluctuation relaxation and the different response of polymer-particle structural correlations to adsorption on the mesoscopic entanglement length scale. The theory is in surprisingly good agreement with recent melt experiments, and new parametric studies are suggested.


[Clustered regularly interspaced short palindromic repeat associated protein genes cas1 and cas2 in Shigella].
To detect the distribution of clustered regularly interspaced short palindromic repeat (CRISPR) associated protein genes cas1 and cas2 in Shigella and to understand the characteristics of CRISPR with relationship between CRISPR and related characteristics on drug resistance. CRISPR associated protein genes cas1 and cas2 in Shigella were detected by PCR, with its products sequenced and compared. The CRISPR-associated protein genes cas1 and cas2 were found in all the 196 Shigella isolates which were isolated at different times and locations in China. Consistencies showed through related sequencing appeared as follows: cas2, cas1 (a) and cas1 (b) were 96.44%, 97.61% and 96.97%, respectively. There were two mutations including 3177129 site(C→G)and 3177126 site (G→C) of cas1 (b) gene in 2003135 strain which were not found in the corresponding sites of Z23 and 2008113. showed that in terms of both susceptibility and antibiotic-resistance, strain 2003135 was stronger than Z23 and 2008113. CRISPR system widely existed in Shigella, with the level of drug resistance in cas1 (b) gene mutant strains higher than in wild strains. Cas1 (b) gene mutation might be one of the reasons causing the different levels of resistance.


Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides.
Proteosomes are hydrophobic, membranous, multimolecular preparations of meningococcal outer membrane proteins that are also B cell mitogens. These characteristics suggested that proteosomes may serve as carrier proteins and adjuvants to enhance peptide immunogenicity. Although high titers of malaria circumsporozoite (CS) antibodies protect against malaria, vaccines thus far tested in humans have been insufficiently immunogenic to be clinically useful. Here it is shown that synthetic CS peptides hydrophobically complexed to proteosomes by way of lauroyl-cysteine become highly immunogenic in mice without other adjuvants. The high titers of antibodies produced and the safety of proteosomes in humans suggest that this novel system is widely applicable for the development of peptide vaccines to protect against many diseases.


Effectiveness of minimum retesting intervals in managing repetitive laboratory testing: experience from a Croatian university hospital.
Inappropriate laboratory retesting can be addressed by implementing minimum retesting intervals (MRI). The aim of our study was to assess the effectiveness of the implemented MRI protocol for inpatients. Minimum retesting intervals were applied for 53 laboratory tests. The overall reduction of test requests, reduction in charges and reagent cost savings, frequency of MRI alert appearance as well as the rate of MRI acceptance and ignorance were calculated for a one-year period. Reasons for violating the MRI rule, hospital departments that contributed mostly to MRI rule violation, and the frequency of MRI violations between routine and emergency laboratory were evaluated. During the one-year period, 106,780 requests violated the MRI rule, which corresponds to 14.8% of all requests received. 13,843 requests were cancelled, yielding a 1.9% reduction of requested tests. High-volume tests, namely complete blood count, C-reactive protein, alanine aminotransferase, gamma-glutamyltransferase and total bilirubin, accounted for 65% of all generated alerts and had the highest alert ignorance (>85%). The highest cancellation rate was observed for tumor markers and autoimmunity tests, for most being at least 50%. Annual charge reduction was 62,641 EUR while reagent cost savings were 11,408 EUR. Tests performed in the emergency laboratory had a higher alert appearance than the same routine tests. The most common reason for MRI violation was clinical justification based on the patient's condition. Most frequently ignored MRI alerts were in the intensive care unit. MRI implementation showed limited effectiveness in reducing testing repetition and achieving financial savings, yet provided the basis for future improvements.


[Rodlet cells of fish in calcium deficiency in the external environment].
The ultrastructure of rodlet cells from the heat kidney of the carp Cyprinus carpio L. and tilapia Oreochromis mossambicus Peters has been studied. All the investigated cells displayed a common structure. The number of rodlet cells increased after exposure of fishes in Ca(2+)-free water or in the water supplemented with NH4+ or Cd2+. The latter were found to suppress Ca(2+)-absorption from the environment.


Anthrax in captive carnivores in Ibadan, Nigeria.
Between 20 and 22 June 1974, three captive carnivores (two genets, Genetta sp. and one caracal, Felis caracal) died suddenly in the University of Ibadan Zoological Garden without previous signs of illness. Bacillus anthracis was isolated from their blood and tissues. The organism was highly pathogenic to laboratory animals. The disease was believed to have been contracted from meat fed the animals.


Current and Future Perspectives of Microscopic and Endoscopic Transsphenoidal Surgery for Pituitary Adenomas: A Narrative Review.
Transsphenoidal resection remains the standard treatment for most pituitary adenomas. However, the ideal surgical approach to safely access these lesions, either microsurgical or endoscopic, continues to be debated. Since the introduction of endoscopic transsphenoidal surgery, centers around the world have increasingly adopted this technique, experiencing a shift away from the conventional microsurgical approach. Large series reporting the efficacy and safety of endoscopic surgery have fueled a growing interest in comparing clinical outcomes between both approaches. Still, proving superiority of either surgical approach remains an elusive task due to the inherent drawbacks of surgical observational studies, as we are still faced with a growing body of evidence reporting conflicting results. Thus, a comprehensive discussion regarding the reach and limitations of both techniques becomes necessary. In this narrative review, we perform a critical appraisal of the literature and provide an expert opinion on the state-of-the-art in transsphenoidal surgery for pituitary adenomas. The advantages and limitations of each approach are assessed and compared from a technical standpoint, and their reported outcomes evaluated in the framework of this transition phase. Available evidence should be interpreted in light of individual patient characteristics and within the context of each medical center, taking into consideration the known impact that surgical expertise and multidisciplinary management hold on clinical outcomes.


Equation to estimate body weight in elderly Mexican women using anthropometric measurements.
Body weight is useful for many medical and nutritional procedures. When it is difficult or impossible to measure body weight in hospitalized/institutionalized elderly, it can be estimated through equations based on anthropometry generated in other countries, although their validity in other contexts has been poorly studied. To create and validate an equation for estimating body weight for both, hospitalized and nursing home residents Mexican elderly women (institutionalized) using anthropometric measurements. A validation study was carried out in elderly women (> or = 60 years old), admitted to the Geriatrics Service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde" during February-April 19th (n = 43) and April 20th-June 2005 (n = 29), and elderly women residing in three nursing homes in the Metropolitan Area of Guadalajara evaluated during June 2003-June 2004 (n = 23). Subjects were weighed using a scale which was adapted to their clinical situation and were anthropometrically assessed. In the first sample, we generated a new equation using multiple regression analyses. Then, the equation was validated in the other two samples. We also estimated weight using Chumlea's equations: in all samples, estimated and actual weights were compared between each other through a paired t-test. A p < 0.05 was considered as significant. Mean ages in each sample were: 84.3 +/- 7.3, 84.4 +/- 9.1, and 84.2 +/- 8.5 years, respectively. Mean actual weights were: 48.2 +/- 13.5, 48.1 +/- 10.1, and 55.0 +/- 12.3 kg, respectively. The resulting equation was: estimated weight = (1.599* knee height) +(1.135* mid arm circumference) + (0.735*calf circumference) + (0.621* tricipital skinfold thickness)-83.123 (R2 = 0.896, p < 0.001). In hospitalized women, there were no significant differences between estimated and actual weight (sample 1:D-0.02 +/- 4.3 kg, p = 0.976; sample 2: D-0.7 +/- 4.2 kg, p = 0.352). In female nursing homes residents (institutionalized women) weight was significantly overestimated (1.9 +/- 3.2 kg p < 0.01), but the mean difference was smaller than the ones found using Chumlea's equations. The developed equation predicted accurately hospitalized elderly women's body weight in our context. In institutionalized elderly women, weight was significantly overestimated. It would be useful to derive equations for different settings.uals who present normal body weight.


Daylight time-resolved photographs of lightning.
Lightning dart leaders and return strokes have been recorded in daylight with both good spatial resolution and good time resolution as part of the Thunder-storm Research International Program. The resulting time-resolved photographs are apparently equivalent to the best data obtained earlier only at night. Average two-dimensional return stroke velocities in four subsequent strokes between the ground and a height of 1400 meters were approximately 1.3 x 10(8) meters per second. The estimated systematic error is 10 to 15 percent.


Identification of amino acids that are critical to the processivity function of respiratory syncytial virus M2-1 protein.
The M2-1 protein of respiratory syncytial virus (RSV) is a transcription processivity factor that is essential for virus replication. The function of RSV M2-1 protein can be examined by using an RSVlacZ minigenome assay in vitro since the expression of the lacZ gene is dependent on M2-1. The M2-1 protein of pneumonia virus of mice (PVM), also a member of the Pneumovirus genus, functions poorly in the RSVlacZ minigenome assay despite conservation of the Cys(3)-His(1) motif at its N terminus and an overall 40% amino acid identity with RSV M2-1. To identify the amino acids responsible for the differences between these two proteins, two chimeric proteins were constructed. The RSV/PVM (RP) M2-1 chimera that contains the N-terminal 30 amino acids from RSV and the remaining C-terminal 148 amino acids from PVM maintained a level of activity at an ca. 36% of RSV M2-1. However, the PVM/RSV (PR) M2-1 chimera with the N-terminal 29 amino acids from PVM and 164 amino acids from RSV had an activity of <5% of RSV M2-1, indicating that the functional determinants are mainly located in the N terminus of M2-1. Mutagenesis of the N terminus of PR M2-1 and RSV M2-1 identified that Leu-16 and Asn-17 of RSV M2-1 are critical to the M2-1 function. In addition, several charged residues in the N terminus of RSV M2-1 also contributed to the functional integrity of M2-1.


Seasonal dietary shifts enhance parasite transmission to lake salmonids during ice cover.
Changes in abiotic and biotic factors between seasons in subarctic lake systems are often profound, potentially affecting the community structure and population dynamics of parasites over the annual cycle. However, few winter studies exist and interactions between fish hosts and their parasites are typically confined to snapshot studies restricted to the summer season whereas host-parasite dynamics during the ice-covered period rarely have been explored. The present study addresses seasonal patterns in the infections of intestinal parasites and their association with the diet of sympatric living Arctic charr (Salvelinus alpinus) and brown trout (Salmo trutta) in Lake Takvatn, a subarctic lake in northern Norway. In total, 354 Arctic charr and 203 brown trout were sampled from the littoral habitat between June 2017 and May 2018. Six trophically transmitted intestinal parasite taxa were identified and quantified, and their seasonal variations were contrasted with dietary information from both stomachs and intestines of the fish. The winter period proved to be an important transmission window for parasites, with increased prevalence and intensity of amphipod-transmitted parasites in Arctic charr and parasites transmitted through fish prey in brown trout. In Arctic charr, seasonal patterns in parasite infections resulted mainly from temporal changes in diet toward amphipods, whereas host body size and the utilization of fish prey were the main drivers in brown trout. The overall dynamics in the community structure of parasites chiefly mirrored the seasonal dietary shifts of their fish hosts.


A Visual Analog Scale for Self-Reported Quality of Life: A Comparison of VAS and QoL-AD in Older Adults.
People with dementia (PWD) are one of the fastest-growing clinical populations for speech-language pathologists. Self-reported quality of life (QoL) assessments are critical patient-reported outcome measures that align with person-centered care principles. However, proxy-reporting is most often used due to assumptions that PWD cannot provide reliable self-report. Visual analog scales (VASs) have been successfully used with people with expressive and cognitive deficits to measure subjective constructs such as QoL, mood, and pain. The purpose of this project is to evaluate the feasibility and reliability of a VAS QoL assessment tool. Twenty older adults free of cognitive impairment were assessed using the quality of life in Alzheimer's disease (QoL-AD) and the QoL-AD in combination with a VAS (VAS QoL-AD). The construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD were assessed by performing both assessments twice, 4 weeks apart. Significant correlations between the overall VAS QoL-AD and the QoL-AD scale ratings, between most of the QoL-AD and VAS QoL-AD subtests, and between the first and second assessment scores were observed. Results indicated strong construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD in people without dementia. These results warrant further research into the development of a dementia-specific, self-reported VAS QoL scale for PWD.


Early Impact of the COVID-19 Pandemic on Outpatient Neurologic Care in Hawai'i.
In March 2020, Hawai'i instituted public health measures to prevent the spread of Coronavirus disease 2019 (COVID-19), including stay-at-home orders, closure of non-essential businesses and parks, use of facial coverings, social distancing, and a mandatory 14-day quarantine for travelers. In response to these measures, Hawai'i Pacific Neuroscience (HPN) modified practice processes to ensure continuity of neurological treatment. A survey of patients was performed to assess the impact of the COVID-19 pandemic and pandemic-related practice processes for quality improvement. Overall, 367 patients seen at HPN between April 22, 2020, and May 18, 2020, were surveyed via telephone. Almost half (49.6%) participated in a telemedicine appointment, with the majority finding it easy to use (87.4%) and as valuable as face-to-face appointments (68.7%). Many (44.5%) patients said they would have missed a health care appointment without the availability of telemedicine, and 47.3% indicated they might prefer to use telemedicine over in-person appointments in the future. Many reported new or worsening mental health problems, including depression (27.6%), anxiety (38.3%), or sleep disturbances (37.4%). A significant number reported worsening of their condition, with 33.1% of patients who experience migraines reporting increased symptom severity or frequency, 45.8% patients with Alzheimer's disease reporting worsened symptoms, 38.5% of patients with Parkinson's disease who had a recent fall, and 50.0% of patients with multiple sclerosis experiencing new or worsened symptoms. Insights from this survey applied to the practice's pandemic-related processes include emphasizing lifestyle modification, screening for changes in mental health, optimizing treatment plans, and continuing the option of telemedicine.


Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence detector (FLD) method for the quantitative determination of selected neurotransmitters in rat brain.
Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances. We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm. Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52-1.84%), inter-day precision (2.47-3.12%), limit of detection (5-30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures. The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583-591.


Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929).
A phase I clinical trial (GOG-9929) examined the safety and efficacy of adjuvant immune-modulation therapy with the checkpoint inhibitor ipilimumab [anti-CTL antigen-4 (anti-CTLA-4)] following chemoradiation therapy (CRT) for newly diagnosed node-positive human papillomavirus (HPV)-related cervical cancer. To better understand the mechanism of action and to identify predictive biomarkers, immunologic and viral correlates were assessed before, during, and after treatment. Twenty-one patients who received CRT and ≥2 doses of ipilimumab and 5 patients who received CRT only were evaluable for translational endpoints. Circulating T-cell subsets were evaluated by multiparameter flow cytometry. Cytokines were evaluated by multiplex ELISA. HPV-specific T cells were evaluated in a subset of patients by IFNγ ELISpot. Expression of the activation markers ICOS and PD-1 significantly increased on T-cell subsets following CRT and were sustained or increased following ipilimumab treatment. Combined CRT/ipilimumab treatment resulted in a significant expansion of both central and effector memory T-cell populations. Genotype-specific E6/E7-specific T-cell responses increased post-CRT in 1 of 8 HPV16+ patients and in 2 of 3 HPV18+ patients. Elevation in levels of tumor-promoting circulating cytokines (TNFα, IL6, IL8) post-CRT was significantly associated with worse progression-free survival. Our data indicate that CRT alone and combined with ipilimumab immunotherapy show immune-modulating activity in women with locally advanced cervical cancer and may be a promising therapeutic option for the enhancement of antitumor immune cell function after primary CRT for this population at high risk for recurrence and metastasis. Several key immune biomarkers were identified that were associated with clinical response.


Increased micronucleus frequencies in surrogate and target cells from workers exposed to crystalline silica-containing dust.
Mining, crushing, grinding, sandblasting and construction are high-risk activities with regard to crystalline silica exposure, especially in developing countries. Respirable crystalline silica (quartz and cristobalite) inhaled from occupational sources has been reclassified as a human carcinogen in 1997 by the International Agency for Research on Cancer. However, the biological activity of crystalline silica has been found to be variable among different industries, and this has formed the basis for further in vivo/in vitro mechanistic research and epidemiologic studies. This study was conducted for genotoxicity evaluation in a population of workers (e.g. glass industry workers, sandblasters, and stone grinders) mainly exposed to crystalline silica in four different workplaces in Turkey. The micronucleus (MN) assay was applied both in peripheral blood lymphocytes (PBL) as a surrogate tissue and in nasal epithelial cells (NEC) as a target tissue of the respiratory tract. Our study revealed significantly higher MN frequencies in the workers (n = 50) versus the control group (n = 29) (P < 0.001) and indicated a significant effect of occupational exposure on MN induction in both of the tissues. For the NEC target tissue, the difference in MN frequencies between the workers and control group was 3-fold, whereas in peripheral tissue, it was 2-fold. Respirable dust and crystalline silica levels exceeding limit values and mineralogical/elemental dust composition of the dust of at least 70% SiO(2) were used as markers of crystalline silica exposure in each of the workplaces. Moreover, 24% of the current workers were found to have early radiographical changes (profusion category of 1). In conclusion, although the PBL are not primary target cells for respiratory particulate toxicants, an evident increase in MN frequencies in this surrogate tissue was observed, alongside with a significant increase in NEC and may be an indicator of the accumulated genetic damage associated with crystalline silica exposure.


The surgical risk of suprapubic catheter insertion and long-term sequelae.
Suprapubic catheter (SPC) insertion is a common urological procedure, which is often referred to as safe and simple even in inexperienced hands. There is, however, very little published evidence on the safety of this procedure. Our study aimed to provide evidence on the associated morbidity and mortality and provide guidance for practising clinicians. A total of 219 patients who underwent SPC insertion under cystoscopic guidance at two urology institutions between 1994 and 2002 were identified and their case notes reviewed. The intra-operative complication rate was 10% and the 30-day complications rate was 19%. Mortality rate was 1.8%. Long-term complications included recurrent UTIs (21%), catheter blockage (25%) resulting in multiple accident and emergency attendance (43%). Despite this, the satisfaction rate was high (72%) and most patients (89%) prefer the SPC over the urethral catheter. SPC bladder drainage results in a high patient satisfaction rate. Patients and clinicians should be aware of the potential complications associated with SPC insertion.


Plant-based analogues identified as potential inhibitor against tobacco mosaic virus: A biosimulation approach.
Benzosuberene compounds with a pyrrolone group adhered to it are compounds extracted from the oils of Cedrus deodara plant, that bear inhibitory capabilities. Tobacco mosaic virus is known to affect crop production every year. The currently known inhibitors against TMV have a weak inhibition effect and also tend to be toxic towards non-target living organisms as well as the environment. Thus, the requirement of non-toxic potent inhibitors is the need of the hour, which led us to test our benzosuberene molecules on the binding site of TMV and check their affinity as well as stability. The non-toxic nature of these molecules has already been experimentally established. Through in-silico analysis involving docking and simulation experiments, we compared the interaction pattern of these ligand molecules with the already present inhibitors. Our investigation proved that the reported ligands (ligands 3, 7, 9, and 17 obtained -177.103, -228.632, -184.134, and - 188.075 kJ/mol binding energies, respectively) interacted with the binding site of TMV much efficiently than the known inhibitors (Ribavirin and Zhao et al. 2020 obtained 121.561 and - 221.393 kJ/mol binding energies, respectively). Moreover, they acquired a stable conformation inside the binding pocket, where a higher number of binding site residues contributed towards interaction. Thus, their structural framework can be optimized for the exploration of their antiviral properties to develop potent botanical viricides against plant virus infection.


COVID-19 booster dose acceptance, hesitancy and concerns among the elderly population: A cross-sectional study.
The COVID-19 pandemic that originated in Wuhan, China in December 2019 results in respiratory and gastrointestinal infections. Elderly patients are at high risk. Preventive measures like avoiding contact with COVID-19 patients and wearing N95 masks can contribute to reducing the risk of infection, but vaccination remains crucial. A cross-sectional survey-based study was conducted among the elderly population (≥ 50 years) in Pakistan. A 16-items questionnaire explored the socio-demographic profile of the participants, including questions about their age, gender, etc. The other sections included questions regarding vaccine registration, vaccine acceptance, and hesitation and fears towards vaccines. The items were developed to collect the data on the basis of the Likert scale. There was a total of 3059 respondents. The majority of the participants (n = 2726, 89.1%) were aged below 70 years, while 10.9% (n = 333) were aged above 70 years. Many participants (47.1%) expressed their concerns about the efficacy of COVID-19 vaccine booster dose. Despite their willingness to vaccinate with the cOVID-19 vaccine, 24.7% female participants expressed concerns related to the safety of the vaccine. Among all the respondents, 23.1% participants had no concerns about the cOVID-19 vaccine booster dose. The study identified a reluctance and lack of confidence in the efficiency of the COVID-19 booster dose. The alarming situation is rigidity towards vaccination among the elderly population. Necessary measures must be taken by the health department of Pakistan to manage this reluctant behavior and increase confidence on the efficiency of the COVID-19 booster dose.


[Myocardosis - myocardia - cardiomyopathy (author's transl)].
"Cardiomyopathy", a term formerly used for heart muscle disease of unknown aetiology, is at present applied to all myocardial diseases other than coronary-heart disease. This definition includes many different forms of metabolic disorders of heart muscle. Four manifestations of metabolic myocardial disease, differing in their aetiology and pathogenesis are distinguished: (1) "transport" myocardosis, (2) "arthrocytotic" myocardosis, (3) myocardia, and (4) idiopathic cardiomyopathy. They are differentiated by combined morphological and quantitative mineral examination. "Transport" myocardosis is the most common form and its particular aetiology can be further specified. Cause of death in patients with metabolic disorders often remains undiscovered even at autopsy. Combination of histological and quantitative mineral analysis of myocardium can further define the particular form.


Complications related to lobectomy in living lobar lung transplant donors.
To evaluate post-operative complications in living lobar lung transplant donors. Between September of 1999 and May of 2005, lobectomies were performed in 32 healthy lung transplant donors for 16 recipients. The medical charts of these donors were retrospectively analyzed in order to determine the incidence of postoperative complications and alterations in pulmonary function after lobectomy. Twenty-two donors (68.75%) presented no complications. Among the 10 donors presenting complications, the most frequently observed complication was pleural effusion, which occurred in 5 donors (15.6% of the sample). Red blood cell transfusion was necessary in 3 donors (9.3%), and 2 donors underwent a second surgical procedure due to hemothorax. One donor presented pneumothorax after chest tube removal, and one developed respiratory infection. There were two intra-operative complications (6.25%): one donor required bronchoplasty of the middle lobe; and another required lingular resection. No intra-operative mortality was observed. Post-operative pulmonary function tests demonstrated an average reduction of 20% in forced expiratory volume in one second (p < 000.1) compared to pre-operative values. Lobectomy in living lung transplant donors presents high risk of post-operative complications and irreversible impairment of pulmonary function. Careful pre-operative evaluation is necessary in order to reduce the incidence of complications in living lobar lung transplant donors.


The Management of Intestinal Penetrating Crohn's Disease.
Crohn's disease (CD) leads to the development of complications through progressive uncontrolled inflammation and the transmural involvement of the bowel wall. Most of the available literature on penetrating CD focuses on the perianal phenotype. The management of nonperianal penetrating complications poses its own set of challenges and can result in significant morbidity and an increased risk of mortality. Few controlled trials have been published evaluating this subgroup of patients for clinicians to use for guidance. Utilizing the available evidence, we review the epidemiology, presentation, and modalities used to diagnosis and assess intestinal fistulas, phlegmons, and abscesses. The literature regarding the medical, endoscopic, and surgical management options are reviewed providing physicians with a therapeutic framework to comprehensively treat these nonperianal penetrating complications. Through a multidisciplinary evidence-based approach to the complex sequela of CD outcomes can be improved and patient's quality of life enhanced.10.1093/ibd/izx108_video1izx108_Video5754037501001.


Characterization of Water Coordination to Ferrous Nitrosyl Complexes with fac-N2O, cis-N2O2, and N2O3 Donor Ligands.
Electron paramagnetic resonance (EPR) experiments were done on a series of S = (3)/2 ferrous nitrosyl model complexes prepared with chelating ligands that mimic the 2-His-1-carboxylate facial triad iron binding motif of the mononuclear nonheme iron oxidases. These complexes formed a comparative family, {FeNO}(7)(N2Ox)(H2O)3-x with x = 1-3, where the labile coordination sites for the binding of NO and solvent water were fac for x = 1 and cis for x = 2. The continuous-wave EPR spectra of these three complexes were typical of high-spin S = (3)/2 transition-metal ions with resonances near g = 4 and 2. Orientation-selective hyperfine sublevel correlation (HYSCORE) spectra revealed cross peaks arising from the protons of coordinated water in a clean spectral window from g = 3.0 to 2.3. These cross peaks were absent for the {FeNO}(7)(N2O3) complex. HYSCORE spectra were analyzed using a straightforward model for defining the spin Hamiltonian parameters of bound water and showed that, for the {FeNO}(7)(N2O2)(H2O) complex, a single water conformer with an isotropic hyperfine coupling, Aiso = 0.0 ± 0.3 MHz, and a dipolar coupling of T = 4.8 ± 0.2 MHz could account for the data. For the {FeNO}(7)(N2O)(H2O)2 complex, the HYSCORE cross peaks assigned to coordinated water showed more frequency dispersion and were analyzed with discrete orientations and hyperfine couplings for the two water molecules that accounted for the observed orientation-selective contour shapes. The use of three-pulse electron spin echo envelope modulation (ESEEM) data to quantify the number of water ligands coordinated to the {FeNO}(7) centers was explored. For this aspect of the study, HYSCORE spectra were important for defining a spectral window where empirical integration of ESEEM spectra would be the most accurate.


Modulation of protein adsorption, vascular cell selectivity and platelet adhesion by mussel-inspired surface functionalization.
A mussel-inspired surface functionalization of the polydopamine (PDA) coating has been demonstrated to be a promising strategy to ensure the biocompatibility of various biomaterials. To explore the multifunctionality of the PDA coating for vascular stents and elucidate the mechanisms by which the PDA coating modulates vascular cell behavior, this study examined the protein adsorption, the responses of endothelial cells (ECs) and smooth muscle cells (SMCs), and platelet adhesion to various PDA-coated surfaces synthesized at varied initial dopamine concentrations. Our results indicate that various PDA coatings present distinct and varied functionalities. The quinone group on the PDA coating induces a substantially higher amount of protein adsorption, which subsequently plays a key role in promoting EC attachment and proliferation by regulating their focal adhesion and stress fiber formation. Meanwhile, the reactive phenolic hydroxyl group on the PDA coating potently inhibits SMC proliferation. In addition, the quinone-regulated fibrinogen adsorption to the PDA coating may increase platelet adhesion. Notably, the PDA coating synthesized at an initial dopamine concentration of 1.0 g L-1 shows the most favorable vascular cell selectivity. These findings shed light on the relationships between surface characteristics, protein adsorption, vascular cell behavior, and platelet adhesion of the PDA coating, which may guide better design of PDA application in vascular stents.


Amino acid composition and amino acid-metabolic network in supragingival plaque.
Dental plaque metabolizes both carbohydrates and amino acids. The former can be degraded to acids mainly, while the latter can be degraded to various metabolites, including ammonia, acids and amines, and associated with acid-neutralization, oral malodor and tissue inflammation. However, amino acid metabolism in dental plaque is still unclear. This study aimed to elucidate what kinds of amino acids are available as metabolic substrates and how the amino acids are metabolized in supragingival plaque, by a metabolome analysis. Amino acids and the related metabolites in supragingival plaque were extracted and quantified comprehensively by CE-TOFMS. Plaque samples were also incubated with amino acids, and the amounts of ammonia and amino acid-related metabolites were measured. The concentration of glutamate was the highest in supragingival plaque, while the ammonia-production was the highest from glutamine. The obtained metabolome profile revealed that amino acids are degraded through various metabolic pathways, including deamination, decarboxylation and transamination and that these metabolic systems may link each other, as well as with carbohydrate metabolic pathways in dental plaque ecosystem. Moreover, glutamine and glutamate might be the main source of ammonia production, as well as arginine, and contribute to pH-homeostasis and counteraction to acid-induced demineralization in supragingival plaque.


Proteomics in Trypanosoma cruzi--localization of novel proteins to various organelles.
The completion of the genome sequence of Trypanosoma cruzi has been followed by several studies of protein expression, with the long-term aim to obtain a complete picture of the parasite proteome. We report a proteomic analysis of an organellar cell fraction from T. cruzi CL Brener epimastigotes. A total of 396 proteins were identified by LC-MS/MS. Of these, 138 were annotated as hypothetical in the genome databases and the rest could be assigned to several metabolic and biosynthetic pathways, transport, and structural functions. Comparative analysis with a whole cell proteome study resulted in the validation of the expression of 173 additional proteins. Of these, 38 proteins previously reported in other stages were not found in the only large-scale study of the total epimastigote stage proteome. A selected set of identified proteins was analyzed further to investigate gene copy number, sequence variation, transmembrane domains, and targeting signals. The genes were cloned and the proteins expressed with a c-myc epitope tag in T. cruzi epimastigotes. Immunofluorescence microscopy revealed the localization of these proteins in different cellular compartments such as ER, acidocalcisome, mitochondrion, and putative cytoplasmic transport or delivery vesicles. The results demonstrate that the use of enriched subcellular fractions allows the detection of T. cruzi proteins that are undetected by whole cell proteomic methods.


Effect of static and dynamic disorder on exciton mobility in oligothiophenes.
The polarized optical absorption spectra of different quaterthiophene single crystals in the energy region of the exciton bands originating from the first molecular transition are reported as measured in the temperatures ranging from 7 to 140 K. The intrinsic higher mobility of the b-polarized 0-0 a(u) exciton both with respect to its replicas and to the a-polarized structures is demonstrated in high quality crystals at the lowest temperatures. The influence of structural disorder on mobility is discussed considering, for the different samples, the measured lineshape and linewidth of the absorption peaks, and the relative lineshift and intensity ratio between the 0-0 a(u) line and its first replica at the lowest temperature. The influence of dynamic disorder is discussed considering the lineshape and linewidth of the measured peaks as a function of temperature for both polarizations in the framework of the exciton-phonon coupling theory.


Single-Walled Carbon Nanotube Sensor Selection for the Detection of MicroRNA Biomarkers for Acute Myocardial Infarction as a Case Study.
MicroRNAs (miRNAs) are single-stranded non-coding short ribonucleic acid sequences that take part in many cellular and biological processes. Recent studies have shown that altered expression of miRNAs is involved in pathological processes, and they can thus be considered biomarkers for the early detection of various diseases. Here, we demonstrate a selection and elimination process of fluorescent single-walled carbon nanotube (SWCNT) sensors for miRNA biomarkers based on RNA-DNA hybridization with a complementary DNA recognition unit bound to the SWCNT surface. We use known miRNA biomarkers for acute myocardial infarction (AMI), commonly known as a heart attack, as a case study. We have selected five possible miRNA biomarkers which are selective and specific to AMI and tested DNA-SWCNT sensor candidates with the target DNA and RNA sequences in different environments. Out of these five miRNA sensors, three could recognize the complementary DNA or RNA sequence in a buffer, showing fluorescence modulation of the SWCNT in response to the target sequence. Out of the three working sensors in buffer, only one could function in serum and was selected for further testing. The chosen sensor, SWCNT-miDNA208a, showed high specificity and selectivity toward the target sequence, with better performance in serum compared to a buffer environment. The SWCNT sensor selection pipeline highlights the importance of testing sensor candidates in the appropriate environment and can be extended to other libraries of biomarkers.


Pathology-MRI Correlations in Diffuse Low-Grade Epilepsy Associated Tumors.
It is recognized that IDH mutation negative, low-grade epilepsy associated tumors (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of either classical dysembryoplastic neuroepithelial tumors (DNT) or typical ganglioglioma. "Nonspecific or diffuse DNT" and more recently "polymorphous low-grade neuroepithelial tumor of the young" have been terms used for these entities. There are few reports on the MRI recognition of these diffuse glioneuronal tumors (dGNT), which is important in planning the extent of surgical resection. In 27 LEATs T1, T2, FLAIR, and postcontrast T1 MRI were evaluated and the pathology reviewed, including immunostaining for NeuN, CD34, MAP2, and IDH1. Each case was then independently classified by pathology or MRI as simple DNT, complex DNT, or dGNT. There was agreement in 23/27 (85%; Kappa score 0.62; p < 0.01). In 4 cases, there was discrepancy in the diagnosis of simple versus complex DNT but 100% agreement achieved for dGNT. DNT showed significantly more expansion of the cortex, cystic change and ventricle extension than dGNT. dGNT showed significantly more subcortical T2w hyperintensity and focal cortical atrophy which correlated on pathology with CD34 expression, cortical neuronal loss and white matter rarefaction. There was no distinct cortical dysplasia component identified by MRI or pathology in any case. This study highlights that dGNT can be reliably discriminated on MRI from DNT.


Lateral tennis elbow: "Is there any science out there?".
As orthopaedic surgeons, we are besieged by myths that guide our treatment of lateral epicondylitis, or "tennis elbow." This extends from the term used to describe the condition to the nonoperative and operative treatments as well. The term epicondylitis suggests an inflammatory cause; however, in all but 1 publication examining pathologic specimens of patients operated on for this condition, no evidence of acute or chronic inflammation is found. Numerous nonoperative modalities have been described for the treatment of lateral tennis elbow. Most are lacking in sound scientific rationale. This has led to a therapeutic nihilism with respect to the nonoperative management of this condition. An examination of the literature can only lead us to believe that most, if not all, common nonoperative therapeutic modalities used for the treatment of tennis elbow are unproven at best or costly and time-consuming at worst. Most of the published literature on the nonoperative treatment of patients with lateral tennis elbow consists of poorly designed trials. The selection criteria are nebulous, the control group is questionably designed, and the number of patients is often too low to avoid a serious loss of study power. These studies therefore have a high beta error, implying an inability to detect a difference between groups, even if one truly existed. If clinical signs and symptoms persist beyond the limit of acceptability of both patient and surgeon, then an array of surgical options are available. These range from a 10-minute office procedure (the percutaneous release of the extensor origin with the patient under local anesthetic) to an extensive joint denervation, in which all radial nerve branches ramifying to the lateral epicondyle are directly or indirectly divided. How is the surgeon to choose, given the fact that most of the published surgical studies are case series of one type of operation or another, consisting of patients operated on and evaluated by the same surgeon, who has a vested interest in his or her own patients' successful outcome? The orthopaedic surgeon therefore has very little on which to "hang his hat" when it comes to objective data to guide treatment of patients with lateral tennis elbow syndrome. In the final analysis we are guided simply by our own subjective viewpoint and clinical experience. In 1999, to have such a common clinical condition have such a paucity of peer-reviewed published data of acceptable scientific quality is disappointing. In this review article we will examine the "myths" of tennis elbow: the name, the salient features on history and physical examination, the diagnostic modalities, the pathology of the "lesion," the anatomy of the lateral elbow and extensor origin and why it has led to such confusion in differential diagnosis, the nonoperative and operative treatment of tennis elbow, and finally the various studies that have been carried out on elbow biomechanics as it relates to the pathoetiology of true "tennis elbow." It is our hope that the reader will emerge with a clearer picture of the pathoetiology of the condition and the scientific rationale (or lack thereof) of the various operative and nonoperative treatment modalities.


[Triptolide affect the methylation status of HL-60cells].
To study the effect of triptolide (TP) on the methylation status of human promyelocytic leukemia cells (HL-60) and explore a preliminary demethylation mechanism. Normal HL-60 cells as control group, the cell proliferation level of HL-60 cells was detected by MTT assay, being treated by different concentration TP (3.125, 6.25, 12.5, 25 nmol/L) for 24 h or 48 h respectively; Choosing the 3.125 nmol/L and the 6.25 nmol/L TP affected HL-60 cells for 48 h, the cell apoptosis rate and cell cycle were determined by flow cytometry, the expressions of death-associated protein kinase 1 (DAPK-1) and methyltransferase DNMT1, DNMT3B mRNA were measured by real time-PCR (RT-PCR), LINE-1, DAPK-1 genes'methylation variations were analyzed by methylation specific PCR (MSP). Compared with control group, the different concentration TP could significantly inhibit the proliferation of HL-60 in a time-dose dependent manner (P<0.05, P<0.01). After being treated by TP for 48 h, the cell early apoptosis rate of control group and 6.250 nmol/L TP group were (2.07 ± 1.91)%, (9.77 ± 3.52)%, respectively (P<0.05); When the TP concentration increased, DAPK-1mRNA expression increased (P<0.01), DNMT1, DNMT3B mRNA expression significantly dampened (P<0.01); the promoter of LINE-1, DAPK-1 genes were hypermethylation state in the control group, after being treated by TP for 48 h, the brightness of LINE-1, DAPK-1 genes'methylation strips weakened, and the non-methylation strips enhanced all in a dose-dependent manner. TP could down-regulate the transcriptional expression of methyltransferase DNMT1/3B genes, indirect action to reduce the degree of DAPK-1, LINE-1 genes mathylation, thus promote DAPK-1 gene expression level and inhibit the HL 60 cell growth.


Duration perception in peripheral vision: Underestimation increases with greater stimuli eccentricity.
Duration perception plays a fundamental role in our daily visual activities; however, it can be easily distorted, even in the retinal location. While this topic has been extensively investigated in central vision, similar exploration in peripheral vision is still at an early stage. To investigate the influence of eccentricity, a commonly used indicator for quantifying retinal location, on duration perception in peripheral vision, we conducted two psychophysical experiments. In Experiment 1, we observed that the retinal location influenced the Point of Subjective Equality (PSE) but not the Weber Fraction (WF) of stimuli appearing at eccentricities ranging from 30° to 70°. Except at 30°, the PSEs were significantly longer than 416.7 ms (25 frames), which was the duration of standard stimuli. This suggested that participants underestimated duration, and this underestimation increased with greater distance from the central fixation point on the retina. To eliminate the potential interference of the central task used in Experiment 1, we conducted a supplementary experiment (Experiment 2) that demonstrated that this central task did not change the underestimation (PSE) but did influence the sensitivity (WF) at an eccentricity of 50°. In summary, our findings revealed a compressive effect of eccentricity on duration perception in peripheral vision: as stimuli appeared more peripheral on the retina, there was an increasing underestimation of subjective duration. Reasons and survival advantages of this underestimation are discussed. Findings provide new insight on duration perception in peripheral vision, highlighting an expanding compressive underestimation effect with greater eccentricity.


A review of bilateral training for upper extremity hemiparesis.
Upper extremity hemiparesis is the most common post-stroke disability. Longitudinal studies have indicated that 30-66% of stroke survivors do not have full arm function 6 months post-stroke. The current gold standard for treatment of mild post-stroke upper limb impairment is constraint-induced therapy but, because of the inclusion criteria, alternative treatments are needed which target more impaired subjects. Bilateral arm training has been investigated as a potential rehabilitation intervention. Bilateral arm training encompasses a number of methods including: (1) bilateral isokinematic training; (2) mirror therapy using bilateral training; (3) device-driven bilateral training; and (4) bilateral motor priming. Neural mechanisms mediating bilateral training are first reviewed. The key bilateral training studies that have demonstrated evidence of efficacy will then be discussed. Finally, conclusions are drawn concerning clinical implications based on the reviewed literature.


Linking LOXL2 to Cardiac Interstitial Fibrosis.
Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxidase like 2 (LOXL2) is responsible for collagen and elastin cross-linking in the heart, and its dysregulation has been pathologically associated with increased fibrosis. Additionally, studies have shown that, LOXL2 expression can be regulated by DNA methylation and histone modification. However, there is a paucity of data on LOXL2 regulation and its role in CVD. As such, this review aims to gain insight into the mechanisms by which LOXL2 is regulated in physiological conditions, as well as determine the downstream effectors responsible for CVD development.


Brief vibrotactile stimulation does not increase cortical oxygen consumption when measured by single inhalation of positron emitting oxygen.
Vibrotactile stimulation of the hand elicits no increase in oxygen consumption commensurate with the increase in blood flow measured in human sensory cortex. To test the hypothesis that previous failures to detect a proportionate increase in oxygen consumption could be an artefact of the sequential bolus, or three-step, method used to measure this parameter in the human brain in vivo, the authors compared the measurements with the results of a novel single bolus, or one-step, method of measuring oxygen consumption. The time of completion of the three-step method was 40 to 50 minutes, whereas the one-step method lasted only 3 minutes. The baseline whole-brain oxygen consumption averaged 185 +/- 32 micromol hg(-1) min(-1) by the three-step method and 153 +/- 15 micromol hg(-1) min(-1) by the one-step method. Vibrotactile stimulation did not elicit a significant increase in oxygen consumption measured by either method. This finding rejects the hypothesis that failure to detect an increase of oxygen consumption could be an artefact caused by limitations of the method used previously. Conversely, it also rejects the hypothesis that observations of an increase of oxygen consumption by the new method are artefacts caused by limitations of the one-step method.


Generalized neural trees for pattern classification.
In this paper, a new neural tree (NT) model, the generalized NT (GNT), is presented. The main novelty of the GNT consists in the definition of a new training rule that performs an overall optimization of the tree. Each time the tree is increased by a new level, the whole tree is reevaluated. The training rule uses a weight correction strategy that takes into account the entire tree structure, and it applies a normalization procedure to the activation values of each node such that these values can be interpreted as a probability. The weight connection updating is calculated by minimizing a cost function, which represents a measure of the overall probability of correct classification. Significant results on both synthetic and real data have been obtained by comparing the classification performances among multilayer perceptrons (MLPs), NTs, and GNTs. In particular, the GNT model displays good classification performances for training sets having complex distributions. Moreover, its particular structure provides an easily probabilistic interpretation of the pattern classification task and allows growing small neural trees with good generalization properties.


Evaluation of the effects of comprehensive reform on primary healthcare institutions in Anhui Province.
In 2009, the Chinese Central Communist Party and the China State Council started to implement comprehensive healthcare reforms. The first round of reforms, involving Anhui province, was from 2009 to 2011, and focused on primary healthcare institutions. This study conducts an initial assessment of the effects of specific parts of the reforms in Anhui. Mixed quantitative and qualitative methods were adopted for data collection. Seven hundred and three health institutions from 15 counties were randomly chosen. The practices, development, effects, problems, and other relevant information related to the reform were classified into four aspects: medicine management; personnel systems and income distribution mechanisms; compensation mechanisms for primary healthcare institutions; and strengthening the primary healthcare system. The effects of reform were analyzed by evaluating changes in compensation channels, visit costs, diagnosis and treatment structure, hardware, structures, efficiency, and behavior. A new system for authorizing drugs resulted in a total of 857 new drugs being accessible at agreed prices through primary healthcare institutions in Anhui. The cost of the average outpatient visit decreased from 35.29 RMB to 31.64 RMB, although for inpatients, the average cost increased from 799.05 RMB to 992.60 RMB. The number of healthcare personnel decreased, but their workloads increased. The total revenue from government sources increased by 41.09%, and the proportion of revenue from drugs decreased by 25.19%. The rate of diagnosis and treatment visits and outpatient visits to primary healthcare institutions increased. Finally, between 2008 and 2010, 1,195 standardized township hospitals, 14,134 village clinics, and 1,234 community health service institutions were constructed. The reform of primary healthcare institutions in Anhui has improved the personnel structures surrounding frontline healthcare workers, increased their incomes, improved work efficiency, and changed the compensation patterns of primary healthcare institutions, improved hardware, reduced drug prices, and, to some extent, improved the diagnosis and treatment structure. However, the reforms have not radically changed the behavior of medical workers or the visit patterns of patients. Approaches such as strengthening performance evaluation, and carrying out initiatives to further mobilize frontline healthcare workers, enhance rational drug use through improved training and educate patients, should be undertaken in the future.


Improving Peer Online Forums (iPOF): protocol for a realist evaluation of peer online mental health forums to inform practice and policy.
Peer online mental health forums are commonly used and offer accessible support. Positive and negative impacts have been reported by forum members and moderators, but it is unclear why these impacts occur, for whom and in which forums. This multiple method realist study explores underlying mechanisms to understand how forums work for different people. The findings will inform codesign of best practice guidance and policy tools to enhance the uptake and effectiveness of peer online mental health forums. In workstream 1, we will conduct a realist synthesis, based on existing literature and interviews with approximately 20 stakeholders, to generate initial programme theories about the impacts of forums on members and moderators and mechanisms driving these. Initial theories that are relevant for forum design and implementation will be prioritised for testing in workstream 2.Workstream 2 is a multiple case study design with mixed methods with several online mental health forums differing in contextual features. Quantitative surveys of forum members, qualitative interviews and Corpus-based Discourse Analysis and Natural Language Processing of forum posts will be used to test and refine programme theories. Final programme theories will be developed through novel triangulation of the data.Workstream 3 will run alongside workstreams 1 and 2. Key stakeholders from participating forums, including members and moderators, will be recruited to a Codesign group. They will inform the study design and materials, refine and prioritise theories, and codesign best policy and practice guidance. Ethical approval was granted by Solihull Research Ethics Committee (IRAS 314029). Findings will be reported in accordance with RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) guidelines, published as open access and shared widely, along with codesigned tools. ISRCTN 62469166; the protocol for the realist synthesis in workstream one is prospectively registered at PROSPERO CRD42022352528.


Classification and Visualization of Physical and Chemical Properties of Falsified Medicines with Handheld Raman Spectroscopy and X-Ray Computed Tomography.
Analytical methods for the detection of substandard and falsified medical products (SFs) are important for public health and patient safety. Research to understand how the physical and chemical properties of SFs can be most effectively applied to distinguish the SFs from authentic products has not yet been investigated enough. Here, we investigated the usefulness of two analytical methods, handheld Raman spectroscopy (handheld Raman) and X-ray computed tomography (X-ray CT), for detecting SFs among oral solid antihypertensive pharmaceutical products containing candesartan cilexetil as an active pharmaceutical ingredient (API). X-ray CT visualized at least two different types of falsified tablets, one containing many cracks and voids and the other containing aggregates with high electron density, such as from the presence of the heavy elements. Generic products that purported to contain equivalent amounts of API to the authentic products were discriminated from the authentic products by the handheld Raman and the different physical structure on X-ray CT. Approach to investigate both the chemical and physical properties with handheld Raman and X-ray CT, respectively, promise the accurate discrimination of the SFs, even if their visual appearance is similar with authentic products. We present a decision tree for investigating the authenticity of samples purporting to be authentic commercial tablets. Our results indicate that the combination approach of visual observation, handheld Raman and X-ray CT is a powerful strategy for nondestructive discrimination of suspect samples.


Characterization of the chicken serotonin N-acetyltransferase gene. Activation via clock gene heterodimer/E box interaction.
The abundance of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) mRNA in the chicken pineal gland exhibits a circadian rhythm, which is translated into a circadian rhythm in melatonin production. Here we have started to elucidate the molecular basis of the circadian rhythm in chicken AANAT (cAANAT). The 5'-flanking region of the cAANAT gene was isolated and found to contain an E box DNA element that confers strong luciferase reporter activity. In transfection experiments using chicken pineal cells, an E box mutation dramatically decreased reporter activity. Northern blot analysis indicated that several putative clock genes (bmal1, Clock, and MOP4) are co-expressed in the chicken pineal gland. bmal1 mRNA is expressed in a rhythmic manner in the chicken pineal gland, with peak levels at early subjective night, coincident with the increase in cAANAT expression. Co-transfection experiments in COS cells demonstrated that chicken BMAL1/CLOCK and human BMAL1/MOP4 heterodimers bound the AANAT E box element and enhanced transcription. These observations suggest that binding of clock gene heterodimers to the cAANAT E box is a critical element in the expression of the cAANAT gene in vitro.


Speciation, phylogeography and evolution of life history and morphology in plethodontid salamanders of the Eurycea multiplicata complex.
Understanding the complex interactions among environment, genotype and ontogeny in determining organismal phenotypes is cental to many biological disciplines. The Eurycea multiplicata complex, endemic to the Interior Highlands (Ozark Plateau and Ouachita Mountains) of eastern North America, comprises a diverse radiation of paedomorphic surface-dwelling (E. tynerensis), metamorphic surface-dwelling (E. multiplicata multiplicata and E. m. griseogaster) and metamorphic subterranean (Typhlotriton spelaeus) hemidactyliine plethodontid salamanders. Portions of two mitochondrial genes, cytochrome-b and NADH dehydrogenase-4, totalling 1818 base pairs (bp) were sequenced for 70 ingroup individuals plus numerous outgroup taxa, to examine the biogeography and relationships among these morphologically disparate species. Results show the E. multiplicata complex to be monophyletic, with its two most divergent clades corresponding to geography, not morphology or life history. Transforming surface-dwelling populations from the Ouachitas (E. m. multiplicata) are sister to the Ozark taxa, including paedomorphic surface-dwelling (E. tynerensis), subterranean (T. spelaeus) and transforming surface-dwelling salamanders assigned to the 'subspecies'E. m. griseogaster. Among Ozark taxa T. spelaeus (deeply nested within Eurycea) is sister to a clade that includes E. m. griseogaster and E. tynerensis. Current taxonomy suggests that paedomorphic populations (E. tynerensis) from the western Ozarks are distinct from nearby transforming populations (E. m. griseogaster). However, paedomorphic and transforming salamanders do not form reciprocally monophyletic groups and many populations share almost identical haplotypes. Ancestral state reconstruction of life history traits shows that paedomorphosis arose independently from three to nine times. Most populations are either completely paedomorphic or completely transforming. This suggests that local habitat parameters strongly influence life history mode in this complex, either facultatively or by selection for particular genotypes.


Life at the academic coalface: validation of a holistic academic workload estimation tool.
This paper reports on research exploring the academic workload and performance practices of Australian universities. This research has identified a suite of activities associated with teaching, research and service, each with an associated time value (allocation). This led to the development of the academic workload estimation tool (AWET). In 2020, to validate the findings, we contacted academics willing to participate further and conducted interviews. We used the AWET to estimate workload for each individual for the previous year and compared it to the workload allocated according to their institutional workload model. Discrepancies were then discussed to ascertain to what extent the AWET was able to capture their work. In general, the participants thought the AWET provided a more realistic estimate of their actual work and highlighted how much is underestimated or unaccounted for by the workload models used within their institutions. It also showed how academic performance policies, focussed primarily on research output, disadvantaged many individuals because they ignored or minimised many scholarly, teaching and service-related tasks inherent in the academic role. Overall, the findings showed the AWET was a useful tool to discuss academic work and assisted them to better capture the complexity and extent of what they did. We offer the AWET as a validated approach for academics to estimate their workload in a holistic and transparent manner. We suggest its implementation institution-wide, along with an aligned performance policy, will facilitate negotiation of reasonable performance expectations. This will rebuild trust in the processes and improve a university's effectiveness.


Response of the left ventricle in coronary artery disease to postextrasystolic potentiation.
Left ventricular volumes and contractile patterns were evaluated during the first sinus beat after a compensatory pause resulting from ventricular arrhythmia and were compared to the second sinus beat (control beat) in order to evaluate the effect of postextrasystolic potentiation. Twelve patients had no evidence of heart disease (group I). Fifty patients had coronary artery disease and included 14 patients (group IIa) with no prior myocardial infarction and a normal left ventricular contractile pattern and 19 pateints (group IIb) with an abnormal contractile pattern. Seventeen pateints (group IIc) had a documented transmural myocardial infarction as well as an abnormal left ventricular contractile pattern. In all patients the first postextrasystolic sinus beat, when compared to the second sinus beat, demonstrated increases in stroke volume and ejection fraction and decrease in end-systolic volume. There were no qualitative changes in the contractile pattern in the immediate postextrasystolic beat in the patients with normal left ventricular function. In both group IIb and group IIc the changes in end-systolic volume, stroke volume and ejection fraction were significantly greater than observed in groups I and IIa. Abnormal wall segments present in the control beat in groups IIb and IIc demonstrated after postextrasystolic potentiation a normal contractile pattern, improved pattern or no change when compared to the control beat. Abnormal wall segments were more likely to revert to normal as a result of postextrasystolic potentiation in group IIb than group IIc. Akinesia was less likely to revert completely to normal than hyposinesia. In 20 of 24 patients the changes in contractile pattern after aortocoronary bypass surgery corresponded to those observed as a result of postextrasystolic potentiation.


Survival of herpes simplex virus in water specimens collected from hot tubs in spa facilities and on plastic surfaces.
Several health spas were closed temporarily because of possible nonvenereal spread of herpes simplex virus (HSV) in spa water at these facilities. We collected water specimens from two health spas and studied them for (1) the presence of HSV; (2) bromine (Br2), chlorine (Cl2), and pH levels; and (3) the ability of HSV to survive in water. No HSV could be isolated from the spa water specimens. Spa water had high levels of Cl2 and Br2, tap water specimens had low levels of Cl2, and distilled water had no detectable Cl2 or Br2. The addition of spa water to laboratory stock virus immediately inactivated the virus. The HSV survived four hours in the tap water and 24 hours in distilled water. The survival of HSV appeared to be related to the free halogen content of water. To approximate the conditions of survival of HSV on plastic-coated benches and seats in spa facilities, HSV was placed on plastic surfaces in a humid atmosphere at 37 to 40 degrees C. The virus was found to survive up to 4.5 hours under these conditions. The survival of HSV from human lesions may be different due to the presence of tissue secretions and proteins. Furthermore, transmission may require other factors, such as rubbing of skin or penetration through abrasions. However, survival of significant amounts of virus for 4.5 hours on plastic surfaces suggests that fomites such as these may be nonvenereal routes of HSV transmission.


Identification of a 160-kD molecule as a component of the basement membrane zone and as a minor bullous pemphigoid antigen.
The antigens in normal human skin defined by antibodies in patients with bullous pemphigoid (BP) were studied by Western immunoblots. Eighteen (90%) of 20 BP sera reacted to a 230-kD antigen. Seven (35%) of the sera reacted to a 160-kD antigen. Two of these reacted only to the 160-kD antigen and five also reacted to the 230-kD antigen. Antibodies to the 160-kD antigen were not present in 25 control sera obtained from normal individuals or patients with other bullous diseases. The 160-kD antigen was present in epidermal extracts of four different specimens of normal human skin but not in dermal extracts or extracts of control cells including melanoma, fibroblasts, lung carcinoma, and colon carcinoma. Monospecific sera with antibodies to either the 230-kD or to the 160-kD antigen reacted solely to their respective target antigens, but not to both, in extracts of epidermis that contained both antigens. The 160-kD antigen broke down to a 140-kD fragment, while the 230-kD antigen was unchanged in the absence of protease inhibitors. Western blot affinity purified antibody to the 160-kD antigen bound only to the basement membrane zone on the epidermal side of 1M NaCl split skin. These results indicate that a 160-kD antigen is a normal component of the basement membrane zone of human skin. The antigen is located on the epidermal side of skin split with 1M NaCl. It is a minor BP antigen, antibodies to which are present in some patients with BP.


Kinetic factors determining conducting filament formation in solid polymer electrolyte based planar devices.
Resistive switching characteristics and conducting filament formation dynamics in solid polymer electrolyte (SPE) based planar-type atomic switches, with opposing active Ag and inert Pt electrodes, have been investigated by optimizing the device configuration and experimental parameters such as the gap distance between the electrodes, the salt inclusion in the polymer matrix, and the compliance current applied in current-voltage measurements. The high ionic conductivities of SPE enabled us to make scanning electron microscopy observations of the filament formation processes in the sub-micrometer to micrometer ranges. It was found that switching behaviour and filament growth morphology depend strongly on several kinetic factors, such as the redox reaction rate at the electrode-polymer interfaces, ion mobility in the polymer matrix, electric field strength, and the reduction sites for precipitation. Different filament formations, resulting from unidirectional and dendritic growth behaviours, can be controlled by tuning specified parameters, which in turn improves the stability and performance of SPE-based devices.