Using variable precision rough set for selection and classification of biological knowledge integrated in DNA gene expression.
DNA microarrays have contributed to the exponential growth of genomic and experimental data in the last decade. This large amount of gene expression data has been used by researchers seeking diagnosis of diseases like cancer using machine learning methods. In turn, explicit biological knowledge about gene functions has also grown tremendously over the last decade. This work integrates explicit biological knowledge, provided as gene sets, into the classication process by means of Variable Precision Rough Set Theory (VPRS). The proposed model is able to highlight which part of the provided biological knowledge has been important for classification. This paper presents a novel model for microarray data classification which is able to incorporate prior biological knowledge in the form of gene sets. Based on this knowledge, we transform the input microarray data into supergenes, and then we apply rough set theory to select the most promising supergenes and to derive a set of easy interpretable classification rules. The proposed model is evaluated over three breast cancer microarrays datasets obtaining successful results compared to classical classification techniques. The experimental results shows that there are not significant differences between our model and classical techniques but it is able to provide a biological-interpretable explanation of how it classifies new samples.


Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells.
Rat pancreatic AR42J cells possess exocrine and neuroendocrine properties. Activin A induces morphological changes and converts them into neuron-like cells. In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. About 25% of the cells were stained by anti-PP antibody. When AR42J cells were incubated with betacellulin, a small portion of the cells were stained positively with antiinsulin and anti-PP antibodies. The effect of betacellulin was dose dependent, being maximal at 2 nM. Approximately 4% of the cells became insulin positive at this concentration, and mRNAs for insulin and PP were detected. When AR42J cells were incubated with a combination of betacellulin and activin A, approximately 10% of the cells became insulin positive. Morphologically, the insulin-positive cells were composed of two types of cells: neuron-like and round-shaped cells. Immunoreactive PP was found in the latter type of cells. The mRNAs for insulin, PP, glucose transporter 2, and glucokinase, but not glucagon, were detected. Depolarizing concentration of potassium, tolbutamide, carbachol, and glucagon-like peptide-1 stimulated the release of immunoreactive insulin. These results indicate that betacellulin and activin A convert amylase-secreting AR42J cells into cells secreting insulin. AR42J cells provide a model system to study the formation of pancreatic endocrine cells.


The use of tissue-engineered skin to demonstrate the negative effect of CXCL5 on epidermal ultraviolet radiation-induced cyclobutane pyrimidine dimer repair efficiency.
Ultraviolet radiation (UVR) is responsible for keratinocyte cancers through the induction of mutagenic cyclobutane pyrimidine dimers (CPDs). Many factors influence CPD repair in epidermal keratinocytes, and a better understanding of those factors might lead to prevention strategies against skin cancer. To evaluate the impact of dermal components on epidermal CPD repair efficiency and to investigate potential factors responsible for the dermal-epidermal crosstalk modulating UVR-induced DNA damage repair in keratinocytes. A model of self-assembled tissue-engineered skin containing human primary keratinocytes and fibroblasts was used in this study. We showed that CPD repair in keratinocytes is positively influenced by the presence of a dermis. We investigated the secretome and found that the cytokine CXCL5 is virtually absent from the culture medium of reconstructed skin, compared with media from fibroblasts and keratinocytes alone. By modulating CXCL5 levels in culture media of keratinocytes, we have shown that CXCL5 is an inhibitor of CPD repair. This work outlines the impact of the secreted dermal components on epidermal UVR-induced DNA damage repair and sheds light on a novel role of CXCL5 in CPD repair.


Activation of Gαq in Cardiomyocytes Increases Vps34 Activity and Stimulates Autophagy.
Receptors that activate the heterotrimeric G protein Gαq are thought to play a role in the development of heart failure. Dysregulation of autophagy occurs in some pathological cardiac conditions including heart failure, but whether Gαq is involved in this process is unknown. We used a cardiomyocyte-specific transgenic mouse model of inducible Gαq activation (termed GαqQ209L) to address this question. After 7 days of Gαq activation, GαqQ209L hearts contained more autophagic vacuoles than wild type hearts. Increased levels of proteins involved in autophagy, especially p62 and LC3-II, were also seen. LysoTracker staining and western blotting showed that the number and size of lysosomes and lysosomal protein levels were increased in GαqQ209L hearts, indicating enhanced lysosomal degradation activity. Importantly, an autophagic flux assay measuring LC3-II turnover in isolated adult cardiomyocytes indicated that autophagic activity is enhanced in GαqQ209L hearts. GαqQ209L hearts exhibited elevated levels of the autophagy initiation complex, which contains the Class III phosphoinositide 3-kinase Vps34. As a consequence, Vps34 activity and phosphatidylinositol 3-phosphate levels were higher in GαqQ209L hearts than wild type hearts, thus accounting for the higher abundance of autophagic vacuoles. These results indicate that an increase in autophagy is an early response to Gαq activation in the heart.


Exploratory study of perceived quality of life with implanted standing neuroprostheses.
Individuals with spinal cord injury (SCI) need options for negotiating architectural barriers, completing essential transfers, and accessing items on high shelves or in cupboards that cannot be reached from the wheelchair or safely managed with reachers. Case Western Reserve University (CWRU) and the Department of Veterans Affairs (VA) have developed an assistive technology device to assist individuals with SCI to stand and transfer. The 8-channel implanted CWRU-VA system enables persons with SCI to exercise, stand, and maneuver in the vicinity of their wheelchairs. Interventions that decrease barriers to mobility and participation can have a significant effect on an individual's perceived quality of life (QOL). This study uses a qualitative research methodology comprised of a series of semi-structured interviews to determine the effects on perceived QOL of an implanted 8-channel functional electrical stimulation (FES) system for standing after SCI. The results reveal that individuals with SCI currently using an implanted FES standing system perceived significant improvements in QOL related to the neuroprosthesis. Implanted neuroprostheses for standing have the potential to improve QOL for veterans living with SCI.


A systematic review of clozapine-associated inflammation and related monitoring.
Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.


The role and benefits of accessing primary care patient records during unscheduled care: a systematic review.
The purpose of this study was to assess the impact of accessing primary care records on unscheduled care. Unscheduled care is typically delivered in hospital Emergency Departments. Studies published to December 2014 reporting on primary care record access during unscheduled care were retrieved. Twenty-two articles met inclusion criteria from a pool of 192. Many shared electronic health records (SEHRs) were large in scale, servicing many millions of patients. Reported utilization rates by clinicians was variable, with rates >20% amongst health management organizations but much lower in nation-scale systems. No study reported on clinical outcomes or patient safety, and no economic studies of SEHR access during unscheduled care were available. Design factors that may affect utilization included consent and access models, SEHR content, and system usability and reliability. Despite their size and expense, SEHRs designed to support unscheduled care have been poorly evaluated, and it is not possible to draw conclusions about any likely benefits associated with their use. Heterogeneity across the systems and the populations they serve make generalization about system design or performance difficult. None of the reviewed studies used a theoretical model to guide evaluation. Value of Information models may be a useful theoretical approach to design evaluation metrics, facilitating comparison across systems in future studies. Well-designed SEHRs should in principle be capable of improving the efficiency, quality and safety of unscheduled care, but at present the evidence for such benefits is weak, largely because it has not been sought.


Immunity debt: Hospitals need to be prepared in advance for multiple respiratory diseases that tend to co-occur.
As SARS-CoV-2 transitions from a pandemic to an endemic presence, a significant rise in respiratory diseases such as influenza and Mycoplasma pneumonia is challenging healthcare systems weakened by the impact of COVID-19. This commentary examines the global resurgence of respiratory pathogens, heightened by the post-pandemic "immunity debt", through an analysis of WHO surveillance data and national health reports. Findings reveal a substantial increase in respiratory illnesses, notably among children, compounded by a shortage of pediatricians and growing antimicrobial resistance. This underscores the need to improve hospital preparedness, optimize clinical responses, and enhance public health strategies to effectively navigate the impending peak of concurrent respiratory infections.


A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion.
Cohesin's structural maintenance of chromosome 1 (Smc1) and Smc3 are rod-shaped proteins with 50-nm long intra-molecular coiled-coil arms with a heterodimerization domain at one end and an ABC-like nucleotide-binding domain (NBD) at the other. Heterodimerization creates V-shaped molecules with a hinge at their centre. Inter-connection of NBDs by Scc1 creates a tripartite ring within which, it is proposed, sister DNAs are entrapped. To investigate whether cohesin's hinge functions as a possible DNA entry gate, we solved the crystal structure of the hinge from Mus musculus, which like its bacterial counterpart is characterized by a pseudo symmetric heterodimeric torus containing a small channel that is positively charged. Mutations in yeast Smc1 and Smc3 that together neutralize the channel's charge have little effect on dimerization or association with chromosomes, but are nevertheless lethal. Our finding that neutralization reduces acetylation of Smc3, which normally occurs during replication and is essential for cohesion, suggests that the positively charged channel is involved in a major conformational change during S phase.


Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: role of La autoantigen in XIAP translation.
X-linked inhibitor of apoptosis protein (XIAP) is a key regulator of programmed cell death triggered by various apoptotic triggers. Translation of XIAP is controlled by a 162-nucleotide (nt) internal ribosome entry site (IRES) element located in the 5' untranslated region of XIAP mRNA. XIAP IRES mediates efficient translation of XIAP under physiological stress and enhances cell protection against serum deprivation and radiation-induced apoptosis. In the present report we describe the assembly of a sequence-specific RNA-protein complex consisting of at least four cytosolic proteins on the XIAP IRES element. We determine that the core binding sequence is approximately 28 nt long and is located 34 nt upstream of the initiation site. Moreover, we identify the La autoantigen as a protein that specifically binds XIAP IRES in vivo and in vitro. The biological relevance of this interaction is further demonstrated by the inhibition of XIAP IRES-mediated translation in the absence of functional La protein. The results suggest an important role for the La protein in the regulation of XIAP expression, possibly by facilitating ribosome recruitment to the XIAP IRES.


No Effect of Acute Eccentric Resistance Exercise on Immune Responses to Influenza Vaccination in Older Adults: A Randomized Control Trial.
Older adults are at elevated risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response. Compare antibody and cell mediated immune responses to influenza vaccination in older adults who performed eccentric resistance exercise immediately prior to vaccination to those who did not exercise. Twenty nine resistance training-naive older adults (20 women, 73.9 ± 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-Op), and seated rest (No-Ex). Exercise consisted of 10 sets of 5 eccentric unilateral repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all received the 2018 quadrivalent influenza vaccine (Seqirus Afluria) in the non-dominant deltoid. Antibody titers against each influenza vaccine strain were determined by hemagglutinin inhibition assays at baseline, 6-, and 24-weeks post-vaccination. Influenza-specific T cells were quantified after stimulation with the vaccine by intracellular cytokine staining. No significant group x time effects were found in antibody responses to any strain (interaction for A/H1N1: p = 0.682; A/H3N2: p = 0.644; B/Colorado/06/2017: p = 0.262; B/Phuket/3073/2013: p = 0.851). Groups did not differ in fold-increase of antibody titers 6- and 24-weeks post-vaccination. Influenza-specific T-cells did not differ between groups at any time (comparison at baseline: p = 0.985; 6-weeks: p = 0.889; 24 weeks: p = 0.857). One subject (Ex-S) reported flu-like symptoms 18 weeks post-vaccination. Acute arm eccentric exercise did not influence antibody titers or cell mediated immune responses to the influenza vaccine delivered post-exercise in older adults. More strenuous exercise may be required for exercise to act as an adjuvant. ClinicalTrials.gov Identifier: NCT03736759.


Interferon-γ exposure of human iPSC-derived neurons alters major histocompatibility complex I and synapsin protein expression.
Human epidemiological data links maternal immune activation (MIA) during gestation with increased risk for psychiatric disorders with a putative neurodevelopmental origin, including schizophrenia and autism. Animal models of MIA provide evidence for this association and suggest that inflammatory cytokines represent one critical link between maternal infection and any potential impact on offspring brain and behavior development. However, to what extent specific cytokines are necessary and sufficient for these effects remains unclear. It is also unclear how specific cytokines may impact the development of specific cell types. Using a human cellular model, we recently demonstrated that acute exposure to interferon-γ (IFNγ) recapitulates molecular and cellular phenotypes associated with neurodevelopmental disorders. Here, we extend this work to test whether IFNγ can impact the development of immature glutamatergic neurons using an induced neuronal cellular system. We find that acute exposure to IFNγ activates a signal transducer and activator of transcription 1 (STAT1)-pathway in immature neurons, and results in significantly increased major histocompatibility complex I (MHCI) expression at the mRNA and protein level. Furthermore, acute IFNγ exposure decreased synapsin I/II protein in neurons but did not affect the expression of synaptic genes. Interestingly, complement component 4A (C4A) gene expression was significantly increased following acute IFNγ exposure. This study builds on our previous work by showing that IFNγ-mediated disruption of relevant synaptic proteins can occur at early stages of neuronal development, potentially contributing to neurodevelopmental disorder phenotypes.


Dynamic changes in amino acid concentration profiles in patients with sepsis.
The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies. Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured. The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively. Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic. ClinicalTrial.gov identifier NCT01818830.


Canakinumab for secondary prevention of atherosclerotic disease.
The widespread prevalence of cardiovascular disease (CVD) and its impact on morbidity and mortality requires effective secondary prevention measures. For years, inflammation has been advocated as a key mediator of atherosclerosis and its associated complications. Drugs for secondary prevention of CVD events include interventions aimed at risk factors control and antithrombotic management, but there is no drug currently recommended that specifically targets inflammation. Recently, the inflammatory hypothesis of atherosclerosis has been confirmed by a randomized clinical trial of canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β. Areas covered: This article reviews the pharmacology of canakinumab, its current clinical development status and upcoming regulatory perspectives. Expert opinion: In the CANTOS trial, canakinumab 150 mg met the pre-specified criteria of statistical significance, showing a reduction in combined cardiovascular events, myocardial infarction, re-hospitalization due to urgent revascularization and any coronary revascularization, but no impact on all-cause or cardiovascular death. There were more death attributed to sepsis or infection with canakinumab than placebo, but fewer reports of arthritis, gout, osteaoarthritis and cancer-related death. Because interleukin-1β is only one of the potential pro-inflammatory pathways that may serve as a target for atherothrombotic protection, other anti-inflammatory drugs may be the object of future investigations. If approved, the initial penetration of canakinumab will face hurdles in view of cost issues, but costs are likely to decrease if the drug loses its present status of orphan drug with the new indication.


Normal differentiation of cultured lens cells after inhibition of gap junction-mediated intercellular communication.
The cells of the vertebrate lens are linked to each other by gap junctions, clusters of intercellular channels that mediate the direct transfer of low-molecular-weight substances between the cytosols of adjoining cells. Although gap junctions are detectable in the unspecialized epithelial cells that comprise the anterior face of the organ, both their number and size are greatly increased in the secondary fiber cells that differentiate from them at the lens equator. In other organs, gap junctions have been shown to play an important role in tissue development and differentiation. It has been proposed, although not experimentally tested, that this may be true in the lens as well. To investigate the function of gap junctions in the development of the lens, we have examined the effect of the gap junction blocker 18beta-glycyrrhetinic acid (betaGA) on the differentiation of primary cultures (both dissociated cell-derived monolayers and central epithelium explants) of embryonic chick lens epithelial cells. We found that betaGA greatly reduced gap junction-mediated intercellular transfer of Lucifer yellow and biocytin throughout the 8-day culture period. betaGA did not, however, affect the differentiation of these cells into MP28-expressing secondary fibers. Furthermore, inhibition of gap junctions had no apparent effect on either of the two other types of intercellular (adherens and tight) junctions present in the lens. We conclude that the high level of gap junctional intercellular communication characteristic of the lens equator in vivo is not required for secondary fiber formation as assayed in culture. Up-regulation of gap junctions is therefore likely to be a consequence rather than a cause of lens fiber differentiation and may primarily play a role in lens physiology.


Hyperbaric oxygen therapy in the management of diabetic lower limb wounds.
Hyperbaric oxygen therapy (HBOT) involves the inhalation of 100 percent oxygen at pressures greater than at sea level. One of the most common indications for HBOT is to aid healing of diabetic foot wounds. All cases of diabetic foot wounds that were seen by the Hyperbaric Medicine Centre in Tan Tock Seng Hospital from May 2005 to March 2006 were analysed in terms of outcome (wound healing) after HBOT. A total of 45 cases of foot ulcers/wounds were analysed. 32 patients had a favourable outcome, giving a success rate of 71 percent. The remaining 13 (28 percent) did not have a favourable outcome to HBOT. The success rate was even more significant as a large number of these patients (34 [77 percent]) were told by their specialist that they were at high risk of a further amputation. No major complications were noted. The experience of the Hyperbaric Medicine Centre in Singapore is consistent with that reported in other centres. With proper patient selection, HBOT, together with a multidisciplinary team of vascular and orthopaedic surgeons, podiatrists, infection disease physicians and endocrinologists, can help reduce the numbers and severity of amputations as well as downtime due to increased wound healing.


Pharmacokinetics of azithromycin in foals after i.v. and oral dose and disposition into phagocytes.
The properties of azithromycin suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2-3-month-old foals. Two weeks later, azithromycin for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin p.o. absorption was variable with a mean systemic availability of 39% (+/-20%). The plasma half-life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin had a very large volume of distribution (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))]. The large V(d) can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin in PMN and alveolar cells. The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily for foals with R. equi pneumonia is recommended for further study.


Neurons with dendrites can perform linearly separable computations with low resolution synaptic weights.
In theory, neurons modelled as single layer perceptrons can implement all linearly separable computations. In practice, however, these computations may require arbitrarily precise synaptic weights. This is a strong constraint since both biological neurons and their artificial counterparts have to cope with limited precision. Here, we explore how non-linear processing in dendrites helps overcome this constraint. We start by finding a class of computations which requires increasing precision with the number of inputs in a perceptron and show that it can be implemented without this constraint in a neuron with sub-linear dendritic subunits. Then, we complement this analytical study by a simulation of a biophysical neuron model with two passive dendrites and a soma, and show that it can implement this computation. This work demonstrates a new role of dendrites in neural computation: by distributing the computation across independent subunits, the same computation can be performed more efficiently with less precise tuning of the synaptic weights. This work not only offers new insight into the importance of dendrites for biological neurons, but also paves the way for new, more efficient architectures of artificial neuromorphic chips.


State dependence, personality, and plants: light-foraging decisions in Mimosa pudica (L.).
Plants make foraging decisions that are dependent on ecological conditions, such as resource availability and distribution. Despite the field of plant behavioral ecology gaining momentum, ecologists still know little about what factors impact plant behavior, especially light-foraging behavior. We made use of the behavioral reaction norm approach to investigate light foraging in a plant species that exhibits rapid movement: Mimosa pudica. We explored how herbivore avoidance behavior in M. pudica (which closes its leaflets temporarily when disturbed) is affected by an individual's energy state and the quality of the current environment and also repeatedly tested the behavior of individuals from two seed sources to determine whether individuals exhibit a "personality" (i.e., behavioral syndrome). We found that when individuals are in a low-energy state, they adopt a riskier light-foraging strategy, opening leaflets faster, and not closing leaflets as often in response to a disturbance. However, when plants are in a high-energy state, they exhibit a plastic light-foraging strategy dependent on environment quality. Although we found no evidence that individuals exhibit behavioral syndromes, we found that individuals from different seed sources consistently behave differently from each other. Our results suggest that plants are capable of making state-dependent decisions and that plant decision making is complex, depending on the interplay between internal and external factors.


T cells facilitate recovery from Venezuelan equine encephalitis virus-induced encephalomyelitis in the absence of antibody.
Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus of the genus Alphavirus that is responsible for a significant disease burden in Central and South America through sporadic outbreaks into human and equid populations. For humans, 2 to 4% of cases are associated with encephalitis, and there is an overall case mortality rate of approximately 1%. In mice, replication of the virus within neurons of the central nervous system (CNS) leads to paralyzing, invariably lethal encephalomyelitis. However, mice infected with certain attenuated mutants of the virus are able to control the infection within the CNS and recover. To better define what role T cell responses might be playing in this process, we infected B cell-deficient microMT mice with a VEEV mutant that induces mild, sublethal illness in immune competent mice. Infected microMT mice rapidly developed the clinical signs of severe paralyzing encephalomyelitis but were eventually able to control the infection and recover fully from clinical illness. Recovery in this system was T cell dependent and associated with a dramatic reduction in viral titers within the CNS, followed by viral persistence in the brain. Further comparison of the relative roles of T cell subpopulations within this system revealed that CD4(+) T cells were better producers of gamma interferon (IFN-gamma) than CD8(+) T cells and were more effective at controlling VEEV within the CNS. Overall, these results suggest that T cells, especially CD4(+) T cells, can successfully control VEEV infection within the CNS and facilitate recovery from a severe viral encephalomyelitis.


The discovery of phenylbenzamide derivatives as Grb7-based antitumor agents.
Grb7 is a non-catalytic protein, the overexpression of which has been associated with the proliferative and migratory potentials of cancer cells. Virtual screening strategies involving a shape-based similarity search, molecular docking, and 2D-similarity searches complemented by experimental binding studies (Thermofluor and isothermal titration calorimetry) resulted in the identification of nine novel phenylbenzamide-based antagonists of the Grb7 SH2 domain. Moderate binding affinities were observed, ranging from K(d)=32.3 μM for lead phenylbenzamide NSC 104999 (1) to K(d)=1.1 μM for a structurally related compound, NSC 57148 (2). Deconvolution of the affinity data into its components revealed differences in lead binding, from being entropy based (lead 1) to enthalpically driven (NSC 100874 (3), NSC 55158 (4), and compound 2). Finally, the lead compound 1 was found to decrease the growth of MDA-MB-468 breast cancer cells, with an IC(50) value of 39.9 μM. It is expected that these structures will serve as novel leads in the development of Grb7-based anticancer therapeutics.


Clinical Correlates of Surveillance Events Detected by National Healthcare Safety Network Pneumonia and Lower Respiratory Infection Definitions-Pennsylvania, 2011-2012.
OBJECTIVE To determine the clinical diagnoses associated with the National Healthcare Safety Network (NHSN) pneumonia (PNEU) or lower respiratory infection (LRI) surveillance events DESIGN Retrospective chart review SETTING A convenience sample of 8 acute-care hospitals in Pennsylvania PATIENTS All patients hospitalized during 2011-2012 METHODS Medical records were reviewed from a random sample of patients reported to the NHSN to have PNEU or LRI, excluding adults with ventilator-associated PNEU. Documented clinical diagnoses corresponding temporally to the PNEU and LRI events were recorded. RESULTS We reviewed 250 (30%) of 838 eligible PNEU and LRI events reported to the NHSN; 29 reported events (12%) fulfilled neither PNEU nor LRI case criteria. Differences interpreting radiology reports accounted for most misclassifications. Of 81 PNEU events in adults not on mechanical ventilation, 84% had clinician-diagnosed pneumonia; of these, 25% were attributed to aspiration. Of 43 adult LRI, 88% were in mechanically ventilated patients and 35% had no corresponding clinical diagnosis (infectious or noninfectious) documented at the time of LRI. Of 36 pediatric PNEU events, 72% were ventilator associated, and 70% corresponded to a clinical pneumonia diagnosis. Of 61 pediatric LRI patients, 84% were mechanically ventilated and 21% had no corresponding clinical diagnosis documented. CONCLUSIONS In adults not on mechanical ventilation and in children, most NHSN-defined PNEU events corresponded with compatible clinical conditions documented in the medical record. In contrast, NHSN LRI events often did not. As a result, substantial modifications to the LRI definitions were implemented in 2015. Infect Control Hosp Epidemiol 2016;37:818-824.


Note on the S-matrix propagation algorithm.
A set of full-matrix recursion formulas for the W --> S variant of the S-matrix algorithm is derived, which includes the recent results of some other authors as a subset. In addition, a special type of symmetry that is often found in the structure of coefficient matrices (W matrices) that appear in boundary-matching conditions is identified and fully exploited for the purpose of increasing computation efficiency. Two tables of floating-point operation (flop) counts for both the new W --> S variant and the old W --> t --> S variant of the S-matrix algorithm are given. Comparisons of flop counts show that in performing S-matrix recursions in the absence of the symmetry, it is more efficient to go directly from W matrices to S matrices. In the presence of the symmetry, however, using t matrices is equally and sometimes more advantageous, provided that the symmetry is utilized.


Exploring Cancer Worry in Adolescent and Young Adult Survivors of Childhood Cancers.
Adolescent and young adult (AYA) survivors of cancers in childhood experience cancer worry, defined as concerns about cancer-related issues such as relapse and late effects of treatment. Cancer worry is an important determinant of successful transition to long-term follow-up care. The primary aim of this study was to identify patient-, cancer-, and treatment-related factors associated with cancer worry in AYA survivors. A secondary aim was to explore and understand inappropriate cancer worry (e.g., worry of developing a late effect when not at risk) in this population. Two hundred and fifty AYA survivors, aged 15–26 years, completed a 6-item Cancer Worry Scale. Selection of factors potentially associated with cancer worry was guided by literature and expert opinion for inclusion in univariable and multivariable regression analyses. Female survivors reported significantly more cancer worry than males did (b=-9.4; 95% CI -14.4 to -4.5; p < 0.001). Survivors treated with the most intensive therapies reported more cancer worry compared with those who received the least intensive therapies (b=-18.5; 95% CI -31.2 to -5.9; p = 0.004). Thirty-one percent of participants had inappropriate worry regarding infertility and/or secondary malignancy. In AYA survivors, female sex and higher treatment intensity were associated with increased cancer worry. Inappropriate worry was prevalent among survivors and may contribute to unnecessary distress. These findings can help identify survivors who are more likely to worry and support the development of appropriate services to reduce the effect of cancer worry on survivor well-being.


Frequency Comb Generation via Cascaded Second-Order Nonlinearities in Microresonators.
Optical frequency combs are revolutionizing modern time and frequency metrology. In the past years, their range of applications has increased substantially, driven by their miniaturization through microresonator-based solutions. The combs in such devices are typically generated using the third-order χ^{(3)} nonlinearity of the resonator material. An alternative approach is making use of second-order χ^{(2)} nonlinearities. While the idea of generating combs this way has been around for almost two decades, so far only few demonstrations are known, based either on bulky bow-tie cavities or on relatively low-Q waveguide resonators. Here, we present the first such comb that is based on a millimeter-sized microresonator made of lithium niobate, that allows for cascaded second-order nonlinearities. This proof-of-concept device comes already with pump powers as low as 2 mW, generating repetition-rate-locked combs around 1064 and 532 nm. From the nonlinear dynamics point of view, the observed combs correspond to Turing roll patterns.


High-Resolution Pharyngeal Manometry and Impedance: Protocols and Metrics-Recommendations of a High-Resolution Pharyngeal Manometry International Working Group.
High-resolution manometry has traditionally been utilized in gastroenterology diagnostic clinical and research applications. Recently, it is also finding new and important applications in speech pathology and laryngology practices. A High-Resolution Pharyngeal Manometry International Working Group was formed as a grass roots effort to establish a consensus on methodology, protocol, and outcome metrics for high-resolution pharyngeal manometry (HRPM) with consideration of impedance as an adjunct modality. The Working Group undertook three tasks (1) survey what experts were currently doing in their clinical and/or research practice; (2) perform a review of the literature underpinning the value of particular HRPM metrics for understanding swallowing physiology and pathophysiology; and (3) establish a core outcomes set of HRPM metrics via a Delphi consensus process. Expert survey results were used to create a recommended HRPM protocol addressing system configuration, catheter insertion, and bolus administration. Ninety two articles were included in the final literature review resulting in categorization of 22 HRPM-impedance metrics into three classes: pharyngeal lumen occlusive pressures, hypopharyngeal intrabolus pressures, and upper esophageal sphincter (UES) function. A stable Delphi consensus was achieved for 8 HRPM-Impedance metrics: pharyngeal contractile integral (CI), velopharyngeal CI, hypopharyngeal CI, hypopharyngeal pressure at nadir impedance, UES integrated relaxation pressure, relaxation time, and maximum admittance. While some important unanswered questions remain, our work represents the first step in standardization of high-resolution pharyngeal manometry acquisition, measurement, and reporting. This could potentially inform future proposals for an HRPM-based classification system specifically for pharyngeal swallowing disorders.


Vamorolone treatment improves skeletal muscle outcome in a critical illness myopathy rat model.
Critical illness myopathy (CIM) is a consequence of modern critical care, leading to skeletal muscle atrophy/paralysis with negative consequences for mortality/morbidity and health care costs. Glucocorticoids (GCs) have been proposed to trigger CIM. Here, we compare outcomes of two GCs, the commonly used prednisolone and the newly developed dissociative vamorolone in response to the intensive care unit (ICU) condition for 5 days, ie, sedation, immobilization, and mechanical ventilation. Rats were divided into a 0-day sham-operated control group, and three groups exposed to 5 days ICU condition during treatment with prednisolone (PRED) or vamorolone (VAM) or none of these GCs (ICU-group). Survival, body and muscle weights, cytokine concentrations, regulation of muscle contraction in single fast- and slow-twitch muscle fibres, myofibrillar protein expression and protein degradation pathways were studied. Critical illness myopathy geno- and pheno-types were confirmed in the ICU group. However, VAM and PRED groups showed reduced atrophy/weakness than the ICU group, and muscle specific differences with more severe negative effects on fast-twitch muscle fibres in the PRED than the other groups. These results show that vamorolone provides a GC intervention superior to typical GCs in improving CIM outcomes. Further, the findings do not support the notion that moderate-dose GC treatment represents a factor triggering CIM.


Inheritance of DDT resistance in species A and B of the Anopheles gambiae complex.
It has been reported that Anopheles gambiae species A is resistant to DDT in Upper Volta and Togo, and DDT resistance has been found in a Sudan strain of species B. The species A strain from Upper Volta was more resistant to DDT than the Togo strain, while the Sudan strain of species B was the least resistant. The expression of resistance is genetically determined, and studies on the mode of inheritance have shown that resistance is inherited as a single dominant gene in the Togo strain of species A and the Sudan strain of species B, but that it is inherited as a single incompletely dominant gene in the Upper Volta strain of species A.


Ultrasound Features of the First Metatarsophalangeal Joint in Gout and Asymptomatic Hyperuricemia: Comparison With Normouricemic Individuals.
The first metatarsophalangeal (MTP1) joint is frequently affected in gout. The aim of this study was to identify ultrasound features of the MTP1 joint in people with gout and people with asymptomatic hyperuricemia compared with normouricemic controls. Participants with gout (n = 23) and asymptomatic hyperuricemia (n = 29), and age- and sex-matched normouricemic control participants (n = 34), underwent a gray-scale and power Doppler ultrasound assessment of bilateral MTP1 joints by a single musculoskeletal radiologist. No participants had clinical evidence of joint inflammation at the time of scanning. The static images were later read by 2 musculoskeletal radiologists for the presence of the double contour sign, tophus, erosion, effusion, synovial hypertrophy, synovitis, and cartilage thickness. Compared to normouricemic control participants, participants with gout and participants with asymptomatic hyperuricemia had more frequent double contour sign (odds ratio [OR] 3.91, P = 0.011 and OR 3.81, P = 0.009, respectively). Participants with gout also had more erosion (OR 10.13, P = 0.001) and synovitis (OR 9.00, P < 0.001) and had greater tophus and erosion diameters (P = 0.035 and P < 0.001, respectively). More severe erosion and synovitis grades and a less severe effusion grade were independently associated with gout compared with asymptomatic hyperuricemia (R2 = 0.65, P < 0.001). Urate deposition, synovitis, and bone erosion are common at the MTP1 joint in people with gout, even in the absence of flare. Although individuals with asymptomatic hyperuricemia lack ultrasound features of inflammation or structural joint changes, they demonstrate a similar frequency of urate deposition.


[Implantation of iliosacral screws. Simulation of optimal placement by 3-dimensional X-ray computed tomography].
Percutaneous iliosacral screws are used advantageously to fix unstable pelvic girdle avoiding the morbidity of open access for conventional screw fixation. The insertion technique must be precise due to the risk of injury to the lumbosacral nerve trunk, the cauda equina roots, and the first sacral nerve. We undertook a study of the implantation site of iliosacral screws looking for a means of standardizing the drilling procedure on the basis of 3D computed tomography (CT) data. A CT series with 3D reconstruction was performed on 11 pelvis bones. We retained pelvis parameters and characterized the axis and narrow zone of the sacral wing. The insertion routes of 6.5 mm cancelous bone screws were simulated: two iliosacral routes fixing S1, and two iliosacroiliac routes fixing S1 and S2. The values of the pelvic parameters and the positions of the screws were compared with the Spearman correlation test and graphic regression. The pelvic incidence was a mean 47 degrees. The length of the sacral wing was a mean 73 mm. The narrow zone of the wing was 47 mm from the lateral iliac fossa. In the narrow zone, the wing section showed an oval shape: 22 mm largest diameter, 11 mm smallest diameter. The wing was oriented 84 degrees in the paracoronal plane perpendicular to the plane of the sacral plate, 67 degrees in the para-axial plane parallel to the sacral plate, and 37 degrees in the sagittal plane of the subject. The length of the upper S1 screw was a mean 80 mm. This upper screw was inclined 89 degrees in the para-coronal plant, 61 degrees in the para-axial plane and 28 degrees in the sagittal plane. The length of the lower S1 screw as a mean 80 mm. This lower screw was inclined 74 degrees in the para-coronal plane, 91 degrees in the para-axial plane and 110 degrees in the sagittal plane. The fixation screws could be inserted in 12 out of 22 cases. Correlations were found with height of the subject, length of the wing and the screw, and screw inclination. The inclination of the upper S1 screw in the para-coronal plane was correlated with the larger diameter of the sacral wing. The pelvis parameters measured were comparable with data in the literature. The very small dimensions of the narrow zone dictate a very precise drilling for the narrow zone. This narrow zone determines the inclination of the screw insertion. In the sagittal plane the standard deviation was very large making it impossible to interpret the data. The route of the upper screw runs obliquely forward in the plane parallel to the sacral plate. The lower screw runs upwardly in the plane perpendicular to the sacral plate. It does not appear possible to insert fixation screws in a routine procedure. Preoperative assessment would be necessary before percutaneous insertion. The 3D CT reconstructions of the sacral wing can be used to determine the precise optimal position of the two iliosacral screws. The principle orientations can be deducted from the plane of the sacral plate. Approximate indications can help reduce operative time and exposure to irradiation (patient and surgeon). Percutaneous iliosacroiliac screw fixation cannot be proposed for all patients.


[Proton irradiation of spontaneous arterio-sinus anastomoses in the cavernous sinus region].
Altogether 10 patients with spontaneous arteriosinusal anastomoses in the cavernous sinus area have been irradiated at the N. N. Burdenko Institute of Neurosurgery, USSR AMS. since 1983 using the synchrotron of the Institute of Theoretical and Experimental Physics. A "piercing" method with a proton beam of 12 mm in diameter (in one case 10 mm) was employed. Nine patients had unilateral anastomoses with the blood supply from branches of the internal and/or external carotid arteries, and one patient had a bilateral anastomosis. Irradiation was given in 2 fractions, in 2-3 days, the maximum total dose was 50-60 Gy. Regression of ophthalmological symptoms was noted 2-3 months after irradiation. Convalescence was noted in 8 patients, a follow-up period in 2 patients was insufficient. Of 7 patients examined by angiography complete thrombosis of the anastomosis was noted in 4, considerable reduction of the blood flow was noted in 3.


Smoking and vulnerability for schizophrenia.
In several countries, the prevalence of smoking among schizophrenia patients is extraordinarily high (70% or greater). A State hospital survey demonstrated that after correcting for other factors, inpatients who have schizophrenia are more likely to be smokers than are persons in the normal population or even other chronic psychiatric inpatients. These findings suggest that neuroleptic treatment and the hospital environment cannot completely explain the high prevalence of smoking. The relationship between smoking and schizophrenia may be explained by a combination of three factors. One factor is the great difficulty for schizophrenia patients to quit smoking. Another is late onset: some schizophrenia patients start to smoke after the onset of psychosis. A third is increased early onset: schizophrenia patients may start daily smoking in greater numbers during adolescence (before the onset of their psychosis) than do persons in the normal U.S. population. Daily smoking is usually considered a sign of nicotine addiction and is used by epidemiological surveys to define the prevalence of smokers (most smokers smoke daily and very few smokers do not smoke every day). The increased early onset suggests that familial factors may increase the prevalence of smoking even among patients who have not yet shown psychotic symptoms. It is hypothesized that smoking among family members in families with genetic loading for schizophrenia may be a marker for those at risk of developing schizophrenia.


The effect of sympathetic stimulation on proximal brachial artery mechanics in humans--differential behaviour within the length of the brachial artery?
The mechanical properties of arteries play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the proximal brachial artery was analysed in 18 healthy volunteers, nine young (25 +/- 2 years) and nine elderly (69 +/- 2 years). A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of the proximal brachial artery diameter in combination with intra-arterial pressure measurements was used to determine wall mechanics. The pressure-diameter (P-D) relationship, distensibility coefficient (DC), compliance coefficient (CC) and stiffness(beta) were obtained at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP). The peripheral vascular resistance increased by 100 and 72%, respectively in the young and elderly during LBNP (P < 0.001). Simultaneously, the mechanical properties of the proximal brachial artery remained unaltered, as estimated from both P-D relationship and stiffness in young (beta-index rest: 5.2 +/- 0.9, LBNP: 5.5 +/- 1.3, NS) as well as elderly (beta-index rest: 13.6 +/- 4.6, LBNP: 16.1 +/- 4.7, NS). LBNP-induced sympathetic activation does not change proximal brachial artery mechanics, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behaviour is within the length of the brachial artery, where the site of transition from elastic to muscular wall structure needs to be specified in future studies.


Human mitochondrial DNA and endogenous bacterial surrogates for risk assessment of graywater reuse.
Previous graywater risk assessment studies have focused on fecal contamination, yet the low density of fecal indicators may not provide the most useful approach to assess pathogen removal during graywater treatment. In this study, we employed high throughput bacterial sequencing and qPCR to elucidate potential microbial surrogates in wastewater sourced from an industrial laundry. In addition, we explored human mitochondrial DNA (HmtDNA) as a new, potentially more reliable molecular marker, because it can be unambiguously sourced, has a high copy number per cell, and is persistent when released from cells with no self-replication in graywater. Pyrosequencing and qPCR revealed that laundry water microbiota was dominated by the skin-associated bacteria Staphylococcus, Corynebacterium, and Propionibacterium (6.5, 5.7, 5.4 log10 copies/100 mL, respectively). While HmtDNA was less abundant (2.8 log10 copies/100 mL), it showed a strong positive correlation with the opportunistic pathogen Staphylococcus aureus (r=0.54, P=3.2×10(-4)) and closely followed a first-order exponential decay model (R2=0.98), remaining detectable in stored laundry graywater for up to 6 days at 20 °C. Based on abundance and persistence, we propose HmtDNA and total Staphylococcus as future laundry graywater treatment surrogates to potentially assess a wide dynamic range of pathogen removal.


Distance to high-voltage power lines and risk of childhood leukemia--an analysis of confounding by and interaction with other potential risk factors.
We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73). We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance.


Invasive Cutaneous Melanoma: Evaluating the Prognostic Significance of Some Parameters Associated with Lymph Node Metastases.
Background and Objectives: This study aimed to assess the clinical-pathological profile of patients with invasive cutaneous melanomas and to identify the parameters with a prognostic role in the lymph nodal spread of this malignant tumor. Materials and Methods: We performed a retrospective study on patients with invasive cutaneous melanomas who underwent surgery in the "Pius Brînzeu" County Clinical Emergency Hospital from Timișoara, Romania, and were evaluated for the status of loco-regional lymph nodes. We selected and analyzed some parameters searching for their relationship with lymph node metastases. Results: We identified 79 patients with invasive cutaneous melanomas (29 men and 50 women, mean age 59.36 years). A percentage of 58.3% of melanomas had Breslow tumor thickness >2 mm; 69.6% of melanomas showed a Clark level IV-V. Tumor ulceration was present in 59.5% of melanomas. A mitotic rate of ≥5 mitoses/mm2 was observed in 48.1% of melanomas. Tumor-infiltrating lymphocytes (TILs), non-brisk, were present in 59.5% of cases and 22.8% of patients had satellite/in-transit metastasis (SINTM). Tumor regression was identified in 44.3% of cases. Lymph nodes metastases were found in 43.1% of patients. Statistical analysis showed that lymph node metastases were more frequent in melanomas with Breslow thickness >2 mm (p = 0.0002), high Clark level (p = 0.0026), mitotic rate >5 mitoses/mm2 (p = 0.0044), ulceration (p = 0.0107), lymphovascular invasion (p = 0.0182), SINTM (p = 0.0302), and non-brisk TILs (p = 0.0302). Conclusions: The Breslow thickness >2 mm, high Clark level, high mitotic rate and ulceration are the most important prognostic factors for lymph nodal spread in cutaneous melanomas. However, some melanomas without these clinical-pathological features can have an unexpected, aggressive evolution, which entails the necessity of close and prolonged clinical follow-up of patients, including those with lesions considered without risk.


Outcome of Reduction of Subcondylar Fracture in Retromandibular Transparotid Approach.
Among all mandibular fracture 25.0 to 40.0% fractures are regarded as condylar and subcondylar fracture. Commonly, reduction of subcondylar fracture is done under general anaesthesia. Different approaches were found for the surgical treatment of condylar fractures besides intraoral approaches such as the pre-auricular, submandibular, rhytidectomy, retromandibular. This is a prospective observational study which was performed to find out the outcome of retromandibular approach for subcondylar fracture treatment of mandible i.e. to find out correction of occlusion and establishment of jaw function, infection, hematoma, salivary fistula, facial nerve damage, haematoma etc complication. Surgical treatment of subcondylar fractures of 15 patients was done in Dhaka Dental College and Hospital and different private centres in Dhaka and Mymensingh, Bangladesh from January 2019 to December 2021 in retromandibular transparortid approach. The patients were evaluated for hematoma, infection, Frey's syndrome, salivary fistula, facial nerve damage, occlusion, fracture site stability, chronic pain in the fracture site and temporomandibular joint movements in the post operative period. Facial nerve injury was not observed. Postoperative swelling of parotid region developed in first two patients. Single patient developed paresis in zygomatic branch of facial nerve causing left upper eyelid muscle weak and after two weeks of physiotherapy it became normal. Salivary fistula developed in three patients which resolved spontaneously. Outcome of this approach like good anatomy and function was found in all cases. Good articular function was obtained in all the cases. By this retromandibular approach condylar fracture reduction; fixation and healing were managed comfortably. However, direct vision of facial nerve fibres has limited the risk of facial nerve injury.


Aortic dissection-induced acute flaccid paraplegia treated with cerebrospinal fluid drainage.
Acute aortic dissection is a life-threatening event in which prompt and correct diagnosis is associated with better outcomes. In most cases, there is chest or back pain. However, in rare cases, patients have little or no pain and other symptoms are more conspicuous at presentation. The autors reports the case of a 47-year-old female patient who sought medical attention for sudden-onset paraplegia. The physical examination was normal except for bilateral lower limb flaccid paralysis, with abolition of deep tendon reflexes and paraesthesia in both feet. Computed tomography showed aortic dissection, with partial thrombosis of the false lumen, starting after the emergence of the left subclavian artery and extending, toward the bifurcation of the aorta, to the left iliac artery. After cerebrospinal fluid drainage, the evolution was favorable.


Demonstration and mapping of highly carbohydrate-dependent epitopes in the herpes simplex virus type 1-specified glycoprotein C.
The carbohydrate dependence of epitopes in the herpes simplex virus type 1-specified glycoprotein C (gC) was studied using a new solid-phase assay procedure. Glycoprotein C, coated on 96-well microtitre plates, was treated with sialidase and increasing concentrations of periodate. A sequential removal of peripheral monosaccharides from the oligosaccharides of gC was ascertained by an enzyme-linked lectin assay. By using a panel of gC-specific monoclonal antibodies in ELISA, it was found that gC contained two types of epitopes differing in their dependence on terminal galactose and sialic acid for expression. Control experiments indicated that the carbohydrate-dependent epitopes were peptide structures and that the carbohydrates did not directly participate in the antibody-binding reaction. The carbohydrate-dependent epitopes were mapped to antigenic site II, according to the proposed nomenclature, whereas those expressed also in the absence of peripheral sugars were located mainly in antigenic site I. These results were compatible with the relative distribution of oligosaccharides in the gC molecule.


The genomic architecture of resistance to Campylobacter jejuni intestinal colonisation in chickens.
Campylobacter is the leading cause of foodborne diarrhoeal illness in humans and is mostly acquired from consumption or handling of contaminated poultry meat. In the absence of effective licensed vaccines and inhibitors, selection for chickens with increased resistance to Campylobacter could potentially reduce its subsequent entry into the food chain. Campylobacter intestinal colonisation levels are influenced by the host genetics of the chicken. In the present study, two chicken populations were used to investigate the genetic architecture of avian resistance to colonisation: (i) a back-cross of two White Leghorn derived inbred lines [(61 x N) x N] known to differ in resistance to Campylobacter colonisation and (ii) a 9(th) generation advanced intercross (61 x N) line. The level of colonisation with Campylobacter jejuni following experimental infection was found to be a quantitative trait. A back-cross experiment using 1,243 fully informative single nucleotide polymorphism (SNP) markers revealed quantitative trait loci (QTL) on chromosomes 7, 11 and 14. In the advanced intercross line study, the location of the QTL on chromosome 14 was confirmed and refined and two new QTLs were identified located on chromosomes 4 and 16. Pathway and re-sequencing data analysis of the genes located in the QTL candidate regions identified potential pathways, networks and candidate resistance genes. Finally, gene expression analyses were performed for some of the candidate resistance genes to support the results. Campylobacter resistance in chickens is a complex trait, possibly involving the Major Histocompatibility Complex, innate and adaptive immune responses, cadherins and other factors. Two of the QTLs for Campylobacter resistance are co-located with Salmonella resistance loci, indicating that it may be possible to breed simultaneously for enhanced resistance to both zoonoses.


Using item response theory with health system data to identify latent groups of patients with multiple health conditions.
A critical step toward tailoring effective interventions for heterogeneous and medically complex patients is to identify clinically meaningful subgroups on the basis of their comorbid conditions. We applied Item Response Theory (IRT), a potentially useful tool to identify clinically meaningful subgroups, to characterize phenotypes within a cohort of high-risk patients. This was a retrospective cohort study using 68,400 high-risk Veteran's Health Administration (VHA) patients. Thirty-one physical and mental health diagnosis indicators based on ICD-9 codes from patients' inpatient, outpatient VHA and VA-paid community care claims. Results revealed 6 distinct subgroups of high-risk patients were identified: substance use, complex mental health, complex diabetes, liver disease, cancer with cardiovascular disease, and cancer with mental health. Multinomial analyses showed that subgroups significantly differed on demographic and utilization variables which underscored the uniqueness of the groups. Using IRT models with clinical diagnoses from electronic health records permitted identification of diagnostic constellations among otherwise undifferentiated high-risk patients. Recognizing distinct patient profiles provides a framework from which insights into medical complexity of high-risk patients can be explored and effective interventions can be tailored.


Cryptic female choice: frogs reduce clutch size when amplexed by undesired males.
In species with internal fertilization, females can 'cryptically' choose (e.g. through sperm selection) which individuals sire their offspring, even when their overt preferences for copulatory partners are overrun by male-male competition and sexual coercion. The experiment presented here reveals that control of paternity after copulation has begun is also possible in species with external fertilization. Females of the hybridogenetic Rana essonae-Rana esculenta (LL-LR) waterfrog complex adjust their clutch size in response to mate type: they release fewer eggs when amplexed by hybrid LR males who--jeopardize successful reproduction--than when amplexed by parental LL males. This reduction in the number of eggs laid can increase a female's residual reproductive value through a second mating in the same breeding season or a larger clutch size in the next year. We argue that cryptic female choice through clutch size adjustment (i) may have evolved more often than previously assumed, and (ii) can arise even where females mate only once during a reproductive period.


Pathology of plaque haemorrhage and neovascularization of coronary artery.
Intraplaque haemorrhage (IPH) is thought to play crucial roles in plaque progression and plaque rupture, resulting in acute coronary syndromes, which are the leading causes of morbidity and mortality in the developed countries. IPH is a common finding in atherosclerotic plaques. In the past decade, the use of anti-Glycophorin A antibodies that specifically and uniquely label membranes of the red cells triggered a cascade of pathologic and experimental studies concordantly documenting not only the presence but also the major role of IPH in plaque progression and complications. Moreover, recent studies have shown that plaque neovascularization is essential to IPH as a source of blood content. Although the mechanisms by which IPH impacts plaque progression and plaque rupture gradually become clear, several questions such as causes of angioneogenesis, identification and treatment of plaques with angioneogenesis are still unanswered. Further studies are needed to resolve these issues; however, the investigation of IPH without a histopathological approach is unconceivable. This review will focus on the pathology of IPH and plaque neovascularization, pathophysiology and potential clinical impact.


The global challenges of surgical congenital anomalies: Evidence, models, and lessons.
The treatment of congenital anomalies (structural birth defects) is common to all the surgical sub-specialties dealing with children. Globally more than 90 % of all babies born with a congenital anomaly are born in middle-and-low-income countries where there is often limited access to needed surgical care. Challenges include lacks of early identification, registry and surveillance systems, missing referral pathways, shortage of trained surgical expertise and insufficient surgical infrastructure. Poverty, transportation logistics, financial constraints and social stigma are also serious barriers for families. There is, however, growing recognition of the priority to expand services, encouraged by the World Health Organization and other global players, and examples of successful models of care. Registry programs are growing, especially in Latin America. The Ponseti method of clubfoot care has been revolutionary on a global scale. The role of not-for-profit non-governmental-organizations has been instrumental in fundraising, training and logistical support as exemplified in the care of oro-facial clefts. Specialized "niche" hospitals are providing needed sub-specialist expertise. The way forward includes the need for effective partnerships, innovative methods to distribute care out from referral hospitals into the districts and the development of national plans embedded in national health policy.


Phase-resolved terahertz self-detection near-field microscopy.
At terahertz (THz) frequencies, scattering-type scanning near-field optical microscopy (s-SNOM) based on continuous wave sources mostly relies on cryogenic and bulky detectors, which represents a major constraint for its practical application. Here, we devise a THz s-SNOM system that provides both amplitude and phase contrast and achieves nanoscale (60-70nm) in-plane spatial resolution. It features a quantum cascade laser that simultaneously emits THz frequency light and senses the backscattered optical field through a voltage modulation induced inherently through the self-mixing technique. We demonstrate its performance by probing a phonon-polariton-resonant CsBr crystal and doped black phosphorus flakes.


Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology.
Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.


Uptake of intraperitoneally administrated triple helical β-glucan for antitumor activity in murine tumor models.
According to the principles of green chemistry and co-efficiency, natural polysaccharides with biological activities, particularly immunoregulation and antitumor activities, have attracted increasing attention. However, the lack of information concerning the pharmacokinetics of polysaccharides is one of the major obstacles limiting their rational clinical use. In this study, triple helical β-glucan (THG), a β-1,6-branched β-1,3-glucan isolated from Lentinus edodes, was studied to clarify its cellular uptake after parenteral (e.g. intraperitoneal) administration and to determine its effect on immune cells in murine tumor models. The results obtained from size exclusion chromatography with static light scattering, differential refractometry and viscometry (SEC-LLS-RI-Vis) and atomic force microscopy (AFM) confirmed that all three THG samples displayed an extended stiff chain conformation with apparent average contour lengths of 598 nm, 510 nm and 117 nm, respectively. The ex vivo results indicated that THG directly promoted cell proliferation of peritoneal macrophages, whole spleen cells and lymphocytes, and activated peritoneal macrophages with TNF-α production. In our findings, the intraperitoneally (i.p.) administrated THG was initially ingested by peritoneal resident macrophages, which transported it to lymph nodes, thymus and even tumor. Simultaneously, THG in macrophages was biodegraded into fragments with granular shapes and small size, which were sufficiently active to be easily ingested by neutrophils. Furthermore, THG fragments could promote the infiltration of macrophages, neutrophils and DCs into tumors, and also activate these cells to enhance their cytotoxicity toward tumor cells, leading to their apoptosis. This study provides important information concerning the ingestion and processing in vivo of triple helical β-glucan from natural products, leading to a better understanding of its antitumor mechanism through activating immune cells in murine tumor models.


Intrinsic Evolution of Analog Circuits Using Field Programmable Gate Arrays.
Evolvable hardware is a field of study exploring the application of evolutionary algorithms to hardware systems during design, operation, or both. The work presented here focuses on the use of field programmable gate arrays (FPGAs), a type of dynamically reconfigurable hardware device typically used for electronic prototyping in conjunction with a newly created open-source platform for performing intrinsic analog evolvable hardware experiments. This work targets the reproduction of seminal field experiments that generated complex analog dynamics of unclocked FPGAs evolved through genetic manipulation of their binary circuit representation: the bitstream. Further, it demonstrates the intrinsic evolution of two nontrivial analog circuits with intriguing properties, amplitude maximization and pulse oscillation, as well as the robustness of evolved circuits to temperature variation and across-chip circuit translation.


Effects of surface interactions on heterogeneous ice nucleation for a monatomic water model.
Despite its importance in atmospheric science, much remains unknown about the microscopic mechanism of heterogeneous ice nucleation. In this work, we perform hybrid Monte Carlo simulations of the heterogeneous nucleation of ice on a range of generic surfaces, both flat and structured, in order to probe the underlying factors affecting the nucleation process. The structured surfaces we study comprise one basal plane bilayer of ice with varying lattice parameters and interaction strengths. We show that what determines the propensity for nucleation is not just the surface attraction, but also the orientational ordering imposed on liquid water near a surface. In particular, varying the ratio of the surface's attraction and orientational ordering can change the mechanism by which nucleation occurs: ice can nucleate on the structured surface even when the orientational ordering imposed by the surface is weak, as the water molecules that interact strongly with the surface are themselves a good template for further growth. We also show that lattice matching is important for heterogeneous nucleation on the structured surface we study. We rationalise these brute-force simulation results by explicitly calculating the interfacial free energies of ice and liquid water in contact with the nucleating surface and their variation with surface interaction parameters.


[Effectiveness of the treatment of chemical burns of the esophagus by local endoscopic laser therapy].
Overall 240 patients with chemical burns of the esophagus were examined. Local endoscopic treatment with the aid of lasers was applied in 180 victims. The efficacy of different types of laser radiation was compared in terms of the times of the healing of the esophageal wall. It is concluded that further studies should be carried out in the given area.


Ericaceous dwarf shrubs affect ectomycorrhizal fungal community of the invasive Pinus strobus and native Pinus sylvestris in a pot experiment.
This study aimed to elucidate the relationship between ericaceous understorey shrubs and the diversity and abundance of ectomycorrhizal fungi (EcMF) associated with the invasive Pinus strobus and native Pinus sylvestris. Seedlings of both pines were grown in mesocosms and subjected to three treatments simulating different forest microhabitats: (a) grown in isolation and grown with (b) Vaccinium myrtillus or (c) Vaccinium vitis-idaea. Ericaceous plants did not act as a species pool of pine mycobionts and inhibited the ability of the potentially shared species Meliniomyces bicolor to form ectomycorrhizae. Similarly, Ericaceae significantly reduced the formation of Thelephora terrestris ectomycorrhizae in P. sylvestris. EcMF species composition in the mesocosms was strongly affected by both the host species and the presence of an ericaceous neighbour. When grown in isolation, P. strobus root tips were predominantly colonised by Wilcoxina mikolae, whereas those of P. sylvestris were more commonly colonised by Suillus and Rhizopogon spp. Interestingly, these differences were less evident (Suillus + Rhizopogon spp.) or absent (W. mikolae) when the pines were grown with Ericaceae. P. strobus exclusively associated with Rhizopogon salebrosus s.l., suggesting the presence of host specificity at the intrageneric level. Ericaceous plants had a positive effect on colonisation of P. strobus root tips by R. salebrosus s.l. This study demonstrates that the interaction of selective factors such as host species and presence of ericaceous plants may affect the realised niche of the ectomycorrhizal fungi.


Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial.
Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs - 0.06 ± 0.14 ng/ml, p < 0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FENa, u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FEK decreased slightly during 3% saline infusion, but simultaneously furosemide increased FEK. U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaCγ decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. (EU Clinical trials register number: 2015-002585-23 , registered on 5th November 2015).


An object cue is more effective than a word in ERP-based detection of deception.
Recent studies of deception have used a form of the guilty knowledge test along with the oddball P300 event-related potential (ERP) to uncover hidden memories. These studies typically have used words as the cuing stimuli. In the present study, a mock crime was enacted by participants to prime their episodic memory and different memory cue types (Words, Pictures of Objects and Faces) were created to investigate their relative efficacy in identifying guilt. A peak-to peak (p-p) P300 response was computed for rare known non-guilty item (target), rare guilty knowledge item (probe) and frequently presented unknown items (irrelevant). Difference in this P300 measure between the probe and irrelevant was the key dependent variable. Object cues were found to be the most effective, particularly at the parietal site. A bootstrap procedure commonly used to detect deception in individual participants by comparing their probe and irrelevant P300 p-p showed the object cues to provide the best discrimination. Furthermore, using all three of the cue types together provided high detection accuracy (94%). These results confirm prior findings on the utility of ERPs for detecting deception. More importantly, they provide support for the hypothesis that direct cueing with a picture of the crime object may be more effective than using a word (consistent with the picture superiority effect reported in the literature). Finally, a face cue (e.g., crime victim) may also provide a useful probe for detection of guilty knowledge but this stimulus form needs to be chosen with due caution.


Clinical and neurobiological factors in the management of treatment refractory attention-deficit hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often continues into adolescence and adulthood. Stimulants such as methylphenidate (MPH) and non-stimulants such as atomoxetine are effective medications for the treatment of ADHD. However, about 30% of patients do not respond to these medications. Pharmacological treatment for ADHD, although highly effective, is associated with marked variabilities in clinical response, optimal dosage needed and tolerability. This article provides an overview of up-to-date knowledge regarding the clinical and neurobiological factors which contribute to and help predict treatment-refractory ADHD. Pharmacogenetic, pharmacogenomics and neuroimaging studies are still controversial with respect to determining the associations between response to medication and genetic factors, thereby resulting in hypotheses that differences in the genetic factors and neuroimaging findings contribute to treatment outcome. Much research on the potential role of genotype in pharmacological effects has focused on the catecholaminergic gene related to executive functions. Many neuroimaging studies have also reported a relationship between treatment response and common patterns of brain structure or activity according to various genetic polymorphisms. When children, adolescents and adults with ADHD do not respond to MPH, we should consider additional pharmacological options, including other classes of psychostimulants, the nonstimulant atomoxetine, bupropion, tricyclic antidepressant, clonidine, guanfacine and lisdexamphetamine. Prudent choice of an appropriate medication and active engagement of children, parents, and teachers in daily management may help to ensure long-term adherence. Therefore, additional research might help to optimize the treatment of children, adolescents and adults with ADHD and to find new options for the treatment of patients who do not respond to stimulants and the other medications. Because these findings should be interpreted cautiously, further studies are needed to elucidate these issues more clearly.


Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcgamma receptors.
The generation of autoantibodies and deposition of immune complexes (ICs) in tissue play a primary role in autoimmune diseases. However, the IC-triggered response consists of complex mechanisms that make it difficult to identify the pathogenesis and develop specific therapy. We clarified here a sequential mechanism for the induction of hypersensitivity angiitis by analyzing the responsible Fc receptor (FcR), effector cells, and mediators in an animal model using FcR-deficient mice. In this model, rheumatoid factor-mediated skin vasculitis was induced in wild-type mice, whereas FcRgamma-deficient mice did not develop the vasculitis. Adoptive transfer of various FcR(+) cells into FcRgamma-deficient mice showed that mast cells but not macrophages derived from wild-type mice triggered skin vasculitis. Mast cells derived from either FcgammaRIII-deficient or tumor necrosis factor (TNF)-deficient mice did not possess the inducibility of skin vasculitis. These results indicate that triggering of vascular inflammation was induced by mast cells through IC binding on FcgammaRIII. TNF produced by such activated mast cells was mainly responsible for the pathogenesis of autoantibody-mediated vasculitis. These findings illustrate the clinical significance of mast cells, Fcgamma receptors, and TNF in IC-induced vasculitis syndrome.


Fuel prices, emission standards, and generation costs for coal vs natural gas power plants.
Low natural gas prices and stricter, federal emission regulations are promoting a shift away from coal power plants and toward natural gas plants as the lowest-cost means of generating electricity in the United States. By estimating the cost of electricity generation (COE) for 304 coal and 358 natural gas plants, we show that the economic viability of 9% of current coal capacity is challenged by low natural gas prices, while another 56% would be challenged by the stricter emission regulations. Under the current regulations, coal plants would again become the dominant least-cost generation option should the ratio of average natural gas to coal prices (NG2CP) rise to 1.8 (it was 1.42 in February 2012). If the more stringent emission standards are enforced, however, natural gas plants would remain cost competitive with a majority of coal plants for NG2CPs up to 4.3.


A three-dimensional model for ciliary motion based on the internal 9+2 structure.
Here we present, to our knowledge, the first modelling platform that enables simulations of three-dimensional (3D) motion of multicilia arrays at a detailed level. It consists of three building blocks: (i) geometric equations for tracking the 3D motion of the cilia, (ii) a hydrodynamic description of the ciliary system, and (iii) model equations for the internal bend generating based on the 9 + 2 structure. The model generates seemingly realistic 3D beat patterns and demonstrates metachronal coordination that evolves autonomously as a result of the hydrodynamic coupling between the cilia. We study the effect of the twisting motion within the cilia and propose a conjecture on a possible role of the radial spokes system.


Whither prometheus' liver? Greek myth and the science of regeneration.
Stem-cell biologists and those involved in regenerative medicine are fascinated by the story of Prometheus, the Greek god whose immortal liver was feasted on day after day by Zeus' eagle. This myth invariably provokes the question: Did the ancient Greeks know about the liver's amazing capacity for self-repair? The authors address this question by exploring the origins of Greek myth and medicine, adopting a 2-fold strategy. First, the authors consider what opportunities the ancient Greeks had to learn about the liver's structure and function. This involves a discussion of early battlefield surgery, the beginnings of anatomical research, and the ancient art of liver augury. In addition, the authors consider how the Greeks understood Prometheus' immortal liver. Not only do the authors examine the general theme of regeneration in Greek mythology, they survey several scholarly interpretations of Prometheus' torture.


An emerging cyberinfrastructure for biodefense pathogen and pathogen-host data.
The NIAID-funded Biodefense Proteomics Resource Center (RC) provides storage, dissemination, visualization and analysis capabilities for the experimental data deposited by seven Proteomics Research Centers (PRCs). The data and its publication is to support researchers working to discover candidates for the next generation of vaccines, therapeutics and diagnostics against NIAID's Category A, B and C priority pathogens. The data includes transcriptional profiles, protein profiles, protein structural data and host-pathogen protein interactions, in the context of the pathogen life cycle in vivo and in vitro. The database has stored and supported host or pathogen data derived from Bacillus, Brucella, Cryptosporidium, Salmonella, SARS, Toxoplasma, Vibrio and Yersinia, human tissue libraries, and mouse macrophages. These publicly available data cover diverse data types such as mass spectrometry, yeast two-hybrid (Y2H), gene expression profiles, X-ray and NMR determined protein structures and protein expression clones. The growing database covers over 23 000 unique genes/proteins from different experiments and organisms. All of the genes/proteins are annotated and integrated across experiments using UniProt Knowledgebase (UniProtKB) accession numbers. The web-interface for the database enables searching, querying and downloading at the level of experiment, group and individual gene(s)/protein(s) via UniProtKB accession numbers or protein function keywords. The system is accessible at http://www.proteomicsresource.org/.


Implications of Agile Values in Software Engineering for Agility in Breast Cancer Treatment: Protocol for a Comparative Study.
Breast cancer treatment has been described as a dynamic and patient-centered approach that emphasizes adaptability and flexibility throughout the treatment process. Breast cancer is complex, with varying subtypes and stages, making it important to tailor treatment plans to each patient's unique circumstances. Breast cancer treatment delivery relies on a multidisciplinary team of health care professionals who collaborate to provide personalized care and quick adaptation to changing conditions to optimize outcomes while minimizing side effects and maintaining the patient's quality of life. However, agility in breast cancer treatment has not been defined according to common agile values and described in language comprehensible to breast cancer professionals. In the rapidly evolving landscape of breast cancer treatment, the incorporation of agile values from software engineering promises to enhance patient care. Our objective is to propose agile values for breast cancer treatment adopted and adapted from software engineering. We also aim to validate how these values conform to the concept of agility in the breast cancer context through referencing past work. We applied a structured research methodology to identify and validate 4 agile values for breast cancer treatment. In the elicitation phase, through 2 interviews, we identified 4 agile values and described them in language that resonates with breast cancer treatment professionals. The values were then validated by a domain expert and discussed in the context of supporting work from the literature. Final validation entailed a domain expert conducting a walkthrough of the 4 identified agile values to adjust them as per the reported literature. Four agile values were identified for breast cancer treatment, and among them, we validated 3 that conformed to the concept of agility. The fourth value, documentation and the quality of documentation, is vital for breast cancer treatment planning and management. This does not conform to agility. However, its nonagility is vital for the agility of the other values. None of the identified agile values were validated as partially conforming to the concept of agility. This work makes a novel contribution to knowledge in identifying the first set of agile values in breast cancer treatment through multidisciplinary research. Three of these values were evaluated as conforming to the concept of agility, and although 1 value did not meet the concept of agility, it enhanced the agility of the other values. It is anticipated that these 4 agile values can drive oncology practice, strategies, policies, protocols, and procedures to enhance delivery of care. Moreover, the identified values contribute to identifying quality assurance and control practices to assess the concept of agility in oncology practice and breast cancer treatment and adjust corresponding actions. We conclude that breast cancer treatment agile values are not limited to 4. RR1-10.2196/53124.


Gibberella konza (Fusarium konzum) sp. nov. from prairie grasses, a new species in the Gibberella fujikuroi species complex.
The Gibberella fujikuroi species complex (Fusarium section Liseola and allied taxa) is composed of an increasingly large number of morphological, biological and phylogenetic species. Most of the known species in this group have been isolated from agricultural ecosystems or have been described from a small number of isolates. We sampled Fusarium communities from native prairie grasses in Kansas and recovered a large number of isolates that superficially resemble F. anthophilum. We used a combination of morphological, biological and molecular characters to describe a new species, Gibberella konza (Gibberella fujikuroi mating population I [MP-I]), from native prairie grasses in Kansas. Although female fertility for field isolates of this species appears to be low, G. konza is heterothallic, and we developed reliably female fertile mating population tester strains for this species. The F. konzum anamorph is differentiated from F. anthophilum and from other Fusarium species in section Liseola by mating compatibility, morphology, AFLP fingerprint profile and differences in β-tubulin DNA sequence.


Survey for hydatidosis in cattle bred in the northern region of the Northern Territory of Australia.
To determine whether hydatidosis occurs in cattle bred in the northern region of the Northern Territory. A survey utilising two stage sampling was designed to provide 95% confidence of detecting hydatids in cattle with a herd prevalence of 10% and animal prevalence of 10%. For a 1 year abattoir killing season, lesions from the liver and/or lung were collected from 4348 cattle being slaughtered at a Northern Territory abattoir and examined for hydatid cysts. The origin of cattle was established through identification of the brand. Sample sizes of 41 or more Northern Territory bred cattle were achieved for each of 29 properties. No hydatid cysts were found in cattle bred in the northern region of the Northern Territory. This study provides evidence that a cycle of hydatid transmission does not occur in the northern region of the Northern Territory.


Phenotypic and Genotypic Traits of Vancomycin-Resistant Enterococci from Healthy Food-Producing Animals.
Food-producing animals may be a reservoir of vancomycin-resistant enterococci (VRE), potentially posing a threat to animal and public health. The aims of this study were to estimate the faecal carriage of VRE among healthy cattle (n = 362), pigs (n = 350), sheep (n = 218), and poultry (n = 102 flocks) in Switzerland, and to characterise phenotypic and genotypic traits of the isolates. VRE were isolated from caecum content of six bovine, and 12 porcine samples respectively, and from pooled faecal matter collected from 16 poultry flock samples. All isolates harboured vanA. Three different types of Tn1546-like elements carrying the vanA operon were identified. Conjugal transfer of vanA to human Enterococcus faecalis strain JH2-2 was observed for porcine isolates only. Resistance to tetracycline and erythromycin was frequent among the isolates. Our data show that VRE harbouring vanA are present in healthy food-producing animals. The vanA gene from porcine isolates was transferable to other enterococci and these isolates might play a role in the dissemination of VRE in the food production chain.


Gas chromatography/ion trap mass spectrometry applied for the determination of polybrominated diphenyl ethers in soil.
A gas chromatography/ion trap mass spectrometry (GC/ITMS) method was developed for the determination of polybrominated diphenyl ethers (PBDEs). ITMS parameters were optimized in order to achieve the best sensitivity for the PBDE analysis. Tandem mass spectrometry, along with an isotope dilution internal standard method, was used for the quantitation. Chromatographic windows were developed for mono- to hepta-BDEs, depending on the retention times when a 30-m GC column was used. A different 15-m column was used to analyze deca-BDE. Environmental soil samples collected from an electronic waste recycling site were prepared by using Soxhlet extraction and column chromatographic cleanup. Average recoveries of 61-118% were obtained for the 13C-labeled PBDE internal standards spiked in the samples prior to sample preparation. The accuracy represented by relative analytical errors was -24% to 18%, and the precision (relative standard deviation) was 11-26% (n=8). The method detection limits ranged from 0.013-0.25 ng/g for the PBDEs in soil.