Bioavailability of biosolids molybdenum to corn.
This study was part of a larger effort to generate field data appropriate to the assessment of biosolids molybdenum (Mo) risk to ruminants. Corn (Zea mays L.) is an important component of cattle diet, and is a logical crop for biosolids amendment owing to its high N requirement. Paired soil and corn stover samples archived from two unique field experiments were analyzed to quantify the relationship (uptake coefficient, UC) between stover Mo and soil Mo load. Both studies used biosolids with total Mo concentrations typical of modern materials. Data from long-term (continuous corn) plots in Fulton County, IL confirm expected low Mo accumulation by corn stover, even at very high biosolids loads and soil Mo loads estimated to be near 18 kg Mo ha(-1). Uptake slopes were actually negative, but USEPA protocol would assign UC values of 0.001. Data from plots in Minnesota also suggested essentially no correlations between stover Mo and soil Mo loads for continuous corn. However, greater Mo accumulation in corn grown following soybean [Glycine max (L.) Merr.] suggests the possibility of enhanced Mo bioavailability to corn in corn-soybean rotations. Nevertheless, molybdenosis risk to cattle consuming corn stover produced on biosolids-amended land is small as stover Mo concentrations were always low and stover Cu to Mo ratios exceeded 2:1, which avoids molybdenosis problems.


Incivility in COVID-19 Vaccine Mandate Discourse and Moral Foundations: Natural Language Processing Approach.
Vaccine hesitancy poses a substantial threat to efforts to mitigate the harmful effects of the COVID-19 pandemic. To combat vaccine hesitancy, officials in the United States issued vaccine mandates, which were met with strong antivaccine discourse on social media platforms such as Reddit. The politicized and polarized nature of COVID-19 on social media has fueled uncivil discourse related to vaccine mandates, which is known to decrease confidence in COVID-19 vaccines. This study examines the moral foundations underlying uncivil COVID-19 vaccine discourse. Moral foundations theory poses that individuals make decisions to express approval or disapproval (ie, uncivil discourse) based on innate moral values. We examine whether moral foundations are associated with dimensions of incivility. Further, we explore whether there are any differences in the presence of incivility between the r/coronaviruscirclejerk and r/lockdownskepticism subreddits. Natural language processing methodologies were leveraged to analyze the moral foundations underlying uncivil discourse in 2 prominent antivaccine subreddits, r/coronaviruscirclejerk and r/lockdownskepticism. All posts and comments from both of the subreddits were collected since their inception in March 2022. This was followed by filtering the data set for key terms associated with the COVID-19 vaccine (eg, "vaccinate" and "Pfizer") and mandates (eg, "forced" and "mandating"). These key terms were selected based on a review of existing literature and because of their salience in both of the subreddits. A 10% sample of the filtered key terms was used for the final analysis. Findings suggested that moral foundations play a role in the psychological processes underlying uncivil vaccine mandate discourse. Specifically, we found substantial associations between all moral foundations (ie, care and harm, fairness and cheating, loyalty and betrayal, authority and subversion, and sanctity and degradation) and dimensions of incivility (ie, toxicity, insults, profanity, threat, and identity attack) except for the authority foundation. We also found statistically significant differences between r/coronaviruscirclejerk and r/lockdownskepticism for the presence of the dimensions of incivility. Specifically, the mean of identity attack, insult, toxicity, profanity, and threat in the r/lockdownskepticism subreddit was significantly lower than that in the r/coronaviruscirclejerk subreddit (P<.001). This study shows that moral foundations may play a substantial role in the presence of incivility in vaccine discourse. On the basis of the findings of the study, public health practitioners should tailor messaging by addressing the moral values underlying the concerns people may have about vaccines, which could manifest as uncivil discourse. Another way to tailor public health messaging could be to direct it to parts of social media platforms with increased uncivil discourse. By integrating moral foundations, public health messaging may increase compliance and promote civil discourse surrounding COVID-19.


Idiopathic granulomatous mastitis: a great imitator?
The patient in this case was seen by numerous doctors for a long time before the diagnosis was made because, right from the start, an abscess or a cancer of the breast was suspected. She was first seen by her general practitioner (GP); thereafter, she went to two consultant physicians and a surgeon in a regional hospital and eventually an idiopathic granulomatous mastitis (IGM) diagnosis was made by a specialist in internal medicine in a university hospital. When the diagnosis IGM was made, the patient was treated with steroids and made a complete recovery. Although the incidence of IGM is not high, the GPs are likely to see these patients initially and should be aware of the existence of this disease, which may spare the patient unnecessary consultations, diagnostics tests or even mastectomy.


AGRICULTURE: Variety Spices Up Chinese Rice Yields.
The results of Chinese field trials reinforce the accepted scientific wisdom that planting different varieties of a crop in the same field holds down the spread of certain diseases and improves yields. And this time researchers seem to have convinced farmers, too.


[Microcirculation of the lungs in histamine administration after vagotomy].
Intravital microscopy was used to study the microcirculatory bed of the lungs during application of histamine after righthand vagotomy. It was discovered that responses occurring at that level during histamine application after intersection of the right vagus were not equivalent to those when the biologically active substance was used in intact animals. Application of histamine without intersection of the nerve was characterized by aggravation of microcirculatory disorders in the lungs as the drug concentration was raised. The reverse was observed in cases where histamine was applied after righthand vagotomy. In this case the most significant alterations in the microcirculatory bed were recorded after local use of low doses of histamine. Besides, the duration of their occurrence was more prolonged as compared to that seen during histamine application in intact animals.


Proof of age required--estimating age in adults without birth records.
Many adults from refugee source countries do not have documents of birth, either because they have been lost in flight, or because the civil infrastructure is too fragile to support routine recording of birth. In Western countries, date of birth is used as a basic identifier, and access to services and support tends to be age regulated. Doctors are not infrequently asked to write formal reports estimating the true age of adult refugees; however, there are no existing guidelines to assist in this task. To provide an overview of methods to estimate age in living adults, and outline recommendations for best practice. Age should be estimated through physical examination; life history, matching local or national events with personal milestones; and existing nonformal documents. Accuracy of age estimation should be subject to three tests: biological plausibility, historical plausibility, and corroboration from reputable sources.


The tropical timber trade and sustainable development.
The tropical timber trade appears to have promoted neither sustained forest management nor sustained forest-based industrialization. The boom-and-bust export pattern is often blamed on demand by developed countries, high import barriers, and low international wood prices. In fact, it is rooted in tropical countries' own policies related to timber concessions and wood-processing industries. These policies suppress timber scarcity signals and must be revised if the trade is to promote sustained economic growth. Even if this is done, the trade may not promote sustained-yield forestry in individual countries.


Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty.
In both rats and primates, including humans, serum levels of insulin-like growth factor I (IGF-I) increase during the onset of puberty, suggesting a role for IGF-I in this process. We examined the ability of IGF-I to affect the release of hypothalamic luteinizing hormone releasing hormone (LHRH) in prepubertal female rats. Our results indicate that IGF-I acts on the median eminence, which contains the highest density of type 1 IGF receptors in the brain, to elicit a dose-related increase in LHRH release. In this regard, a minimal effective dose of 10 ng/ml (p less than 0.05) and a maximal effective dose of 100 ng/ml (p less than 0.01) was observed. IGF-II and insulin were one order of magnitude less effective. The results demonstrate that IGF-I has the capability to act directly upon the median eminence to effect release of LHRH, thereby suggesting a role for IGF-I in facilitating peripubertal changes in LHRH release. Thus, IGF-I may represent one of the 'metabolic signals' thought to be involved in the initiation of puberty.


Longitudinal sensitivity to change of MRI-based muscle cross-sectional area versus isometric strength analysis in osteoarthritic knees with and without structural progression: pilot data from the Osteoarthritis Initiative.
Biomechanical measurement of muscle strength represents established technology in evaluating limb function. Yet, analysis of longitudinal change suffers from relatively large between-measurement variability. Here, we determine the sensitivity to change of magnetic resonance imaging (MRI)-based measurement of thigh muscle anatomical cross sectional areas (ACSAs) versus isometric strength in limbs with and without structural progressive knee osteoarthritis (KOA), with focus on the quadriceps. Of 625 "Osteoarthritis Initiative" participants with radiographic KOA, 20 had MRI cartilage and radiographic joint space width loss in the right knee isometric muscle strength measurement and axial T1-weighted spin-echo acquisitions of the thigh. Muscle ACSAs were determined from manual segmentation at 33% femoral length (distal to proximal). In progressor knees, the reduction in quadriceps ACSA between baseline and 2-year follow-up was -2.8 ± 7.9 % (standardized response mean [SRM] = -0.35), and it was -1.8 ± 6.8% (SRM = -0.26) in matched, non-progressive KOA controls. The decline in extensor strength was more variable than that in ACSAs, both in progressors (-3.9 ± 20%; SRM = -0.20) and in non-progressive controls (-4.5 ± 28%; SRM = -0.16). MRI-based analysis of quadriceps muscles ACSAs appears to be more sensitive to longitudinal change than isometric extensor strength and is suggestive of greater loss in limbs with structurally progressive KOA than in non-progressive controls.


Hydrogen bonding of dimethylpyridine clusters in water: Correlation between the lower consolute solution temperature and electron interaction energy.
We examine the ordering of the Lower Consolute Solution Temperatures (LCSTs) for a set of dimethylpyridines. Density functional theory (DFT) is used. The equilibrium geometries and binding energies of dimers, each comprised of a pair of dimethylpyridines in a sandwich conformation and one H2O molecule at a pivotal site between the nitrogens (the 2:1 dimer), are calculated. It was shown previously that dimer formation in the water-rich zone of the phase diagram has a crucial role in dimethylpyridine demixing. In the resulting dimer diffusion, large hydrophobic clusters of mostly organic content, which expel water and promote phase separation, are assembled. In this description, phase separation requires the formation of 2:1 dimers, but it is the cleavage of hydrogen bonds of the neighboring H2O molecules, which stimulates the diffusion and the subsequent separation dynamics at the LCST. In the present study, we investigate this model and calculate the interaction strength of the external hydrogen bonds. This is obtained as the difference in electronic energy between the 2:1 dimer and the dimer augmented by one or two H2O molecules. The results are compared to the known LCST hierarchy in five dimethylpyridines (DMP): 2,6-DMP > 2,4-DMP > 2,5-DMP > 3,4-DMP > 3,5-DMP. The complexes are derived using high level Kohn-Sham DFT including dispersion terms. The hydrophobic-hydrophilic properties are accounted for by the solvation model, employed for the mixed medium of 60%-water and 40%-organic content. This is simulated by combination of model descriptors of water and DMP in the parameterization scheme of the polarizable continuum model. The calculation results agree with the experimental evidence.


Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala.
A number of experimental results has pointed to a cholinergic involvement in the stress response. Recently, analytical techniques have become available to measure acetylcholine release in vivo during exposure to various stressors. In these experiments, microdialysis was used to monitor acetylcholine output every 15 min in the dorsal hippocampus, amygdala, nucleus accumbens and prefrontal cortex before, during and after 1 h of restraint, including a 15-min session of intermittent tail-shock (1/min, 1 mA, 1-s duration) in rats. In response to the stressful event, acetylcholine release was significantly increased in the prefrontal cortex (186%; p < 0.01) and hippocampus (168%; P < 0.01) but not in the amygdala or nucleus accumbens. The sole effects observed in the amygdala and nucleus accumbens occurred upon release from the restrainer, at which point acetylcholine levels were significantly elevated in both areas (amygdala: 150%; P < 0.05; nucleus accumbens: 13%; P < 0.05). An enhanced acetylcholine release was also evident during this sample period in the hippocampus and prefrontal cortex. These data demonstrate an enhancement of cholinergic activity in response to stress in two acetylcholine projection systems (hippocampus and prefrontal cortex) but not in the intrinsic acetylcholine system of the nucleus accumbens or the extrinsic innervation of the amygdala. Moreover, the data showed that relief from stress was accompanied by a more ubiquitous acetylcholine response that extended to each site tested.


Treatment of advanced urothelial carcinoma with M-VECA (methotrexate, vinblastine, epirubicin and carboplatin).
Transitional cell carcinoma of the urinary tract is actually considered very sensitive to cisplatin-containing regimens. Nevertheless, the generally impaired renal function and poor performance status of these patients are responsible for the severe toxicity usually occurring when cisplatin, either alone or in combination with other agents, is administered to these patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin, and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance. Thirty-five patients with advanced urothelial tract carcinoma were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/m2 iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epirubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every 4 weeks (M-VECA). All patients had bidimensionally measurable disease. Of the 32 evaluable patients, 5 (16%) obtained a complete response and 10 (31%) a partial response (response rate: 47% C.I. = 30%-64%). Grade III-IV leuko-thrombocytopenia was observed in 25%, and mucositis in 19% of cases. Nevertheless, recovery was prompt and opportune dosage reductions avoided severe toxicity in subsequent cycles in most patients. In conclusion, M-VECA is a safe and effective regimen for the treatment of patients with metastatic urothelial tumors.


[Creatine kinase and intramuscular application of drugs (author's transl)].
The diagnosis of infarcts has been improved by inclusion of serum enzyme determinations, among other things. The determination of creatine phosphokinase (CPK) plays a particular role in hospital routine. In the present paper, the effect of intramuscular application of drugs on the serum CPK values is investigated. It is shown that an intramuscular injection is followed by a rise of serum CPK to pathological levels, so that CPK determination loses its significance in differential diagnosis.


Risk factors for relapse or persistence of bacteraemia caused by Enterobacter spp.: a case-control study.
Enterobacter spp. possess chromosomal AmpC beta-lactamases that may be expressed at high levels. Previous studies have demonstrated a risk of relapsed bacteraemia following therapy with third generation cephalosporins (3GCs). What additional factors predict microbiological failure in Enterobacter bacteraemia is unclear. We aimed to determine factors associated with microbiological failure in Enterobacter bacteraemia. We retrospectively identified cases of bacteraemia caused by Enterobacter spp. occurring in four hospitals. Using a case-control design, we determined clinical risk factors for persistence or relapse defined as repeated positive blood cultures collected between 72 hours and up to 28 days post initial positive blood culture. During the study period a total of 922 bacteraemia events caused by Enterobacter spp. in adults were identified. The overall risk of relapsed or persisting bacteraemia at 28 days was low (31 of 922, 3.4%), with only 2 patients experiencing emergent resistance to 3GCs. A total of 159 patients were included in the case-control study. Using multivariate logistic regression, independent predictors for relapse were a line-associated source of infection (OR 3.87; 95% CI 1.56-9.60, p = 0.004) and the presence of immunosuppression (OR 2.70; 95% CI 1.14-6.44, p = 0.02). On univariate analysis definitive therapy with a broad-spectrum beta-lactam-beta-lactamase inhibitor (BLBLI, e.g. piperacillin-tazobactam) was not associated with relapse (OR 1.83; 95% CI 0.64-5.21, p = 0.26) although the proportion of patients receiving a BLBLI as definitive therapy was relatively small (21/159, 13.2%). The risk of relapsed or persistent Enterobacter bacteraemia appears to be low in Australia. A line-associated source of infection and immunocompromise were significant independent predictors for relapse. Larger, preferably randomized, studies are needed to address whether BLBLIs represent an effective carbapenem-sparing option for Enterobacter bacteraemia.


The appearance of carbohydrate-rich material in the developing Golgi apparatus of amoebae.
The silver proteinate reaction was used to stain carbohydrate-rich substances in normal Amoeba proteus and in the developing Golgi apparatus of renucleated amoebae. Normal cells contained stained material, which probably is glycoprotein, in the cell surface, cisternae at the concave pole of the Golgi apparatus, and cytoplasmic vesicles and vacuoles. Previous radioautographic studies had shown tht glycosylation occurs in the Golgi apparatus, and that material in the Golgi apparatus is precursor to the cell surface. Amoebae were enucleated for 5 d, which results in a decline of the Golgi apparatus, the disappearance of the glycoprotein-containing cisternae preceding that of the rest of the organelle. A new nucleus was then transplanted into the enucleate amoebae, bringing about the regeneration of the Golgi apparatus. small curved cisternae that appeared 30 min after renucleation lacked staining with silver proteinate. By 1 h after renucleation, however, the content of cisternae toward the concave poles of Golgi bodies stained with silver proteinate. The Golgi apparatus in cells fixed 6 h and 1 d after operation resembled that of normal amoebae in both morphology and staining pattern. The results suggest that the developing Golgi apparatus acquired the capacity to participate in assembly of cell-surface material within 1 h after renucleation. This occurred before development of the normal enzymic activity of the Golgi apparatus was completed.


Regulation of the unfolded protein response by microRNAs.
The unfolded protein response (UPR) is an adaptive response to the stress that is caused by an accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER). It is an important component of cellular homeostasis. During ER stress, the UPR increases the protein-folding capacity of the endoplasmic reticulum to relieve the stress. Failure to recover leads to apoptosis. Specific cellular mechanisms are required for the cellular recovery phase after UPR activation. Using bioinformatics tools, we identified a number of microRNAs that are predicted to decrease the mRNA expression levels for a number of critical components of the UPR. In this review, we discuss the potential role of microRNAs as key regulators of this pathway and describe how microRNAs may play an essential role in turning off the UPR after the stress has subsided.


Multixenobiotic response of Collembola to soil contamination, the phisiological basis for bioindicative environmental monitoring.
Collembola are well-established models in ecotoxicological research, extensively employed to investigate the effects of various contaminants, including heavy metals. The Multixenobiotic Resistance Mechanism (MXR) is a physiological response based on transmembrane efflux proteins that play a pivotal role in pumping xenobiotics and conferring resistance. This mechanism is firmly established as a biomarker of aquatic contamination and has recently shown promise as a soil biomonitoring tool. In this study, we aimed to assess the feasibility of utilizing the MXR mechanism as a biomonitoring tool, specifically by investigating the response of two Collembola species exposed to soil contaminated in a real-life situation. Soil samples were obtained from the site of Brazil's largest mine disaster, a dam rupture in Brumadinho-MG. We explored MXR activity in the model species Folsomia candida and a tropical native species, Cyphoderus sp. Our findings reveal efflux activity in both species, confirmed by model MXR protein inhibitors. Moreover, we observed distinct MXR activity levels corresponding to the degree of heavy metal contamination in the soil samples. Consequently, our results underscore the potential of combining an established soil bioindicator, such as Collembola, with the physiological response of a molecular biomarker like MXR. This approach may represent a valuable strategy for biomonitoring terrestrial ecosystems.


Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome.
The virion-associated protein of human immunodeficiency virus, type 1 (HIV-1), Vpr, is a small protein with 96 amino acid residues that has the ability to modulate transcription of HIV-1 long terminal repeat (LTR) promoter activity and affects several cellular functions. In this study we have employed molecular approaches to further investigate the mechanism by which Vpr exerts its regulatory effect upon the LTR. We show that by structural and functional interaction with Tat, a potent viral regulatory protein, Vpr synergistically enhances the transcriptional activity of the HIV-1 LTR. Because Tat utilizes cyclin T1 and its partner, CDK9 to elevate the level of transcription from the LTR, we examined the cooperativity between Vpr, Tat, and cyclin T1/CDK9 on viral gene transcription. Results from co-transfection studies indicated superactivation of LTR by Tat and cyclin T1/CDK9 in the presence of wild type Vpr. This activation was not observed with the R73S mutant of Vpr, which contains arginine to serine transition at residue 73. Interestingly, expression of R73S mutant in cells exerts a negative effect on the observed superactivation of the LTR by Tat, cyclin T1/CDK9, and wild type Vpr. Results from protein-protein interaction studies indicated that Vpr is associated with both Tat and cyclin T1 in cells expressing these proteins. Use of deletion mutant proteins in binding studies revealed that the binding sites for Tat and Vpr within cyclin T1 are distinct and that association of these two viral proteins with cyclin T1 is independent from each other. These observations suggest a working model on the cooperative interaction of Vpr with viral and cellular proteins and its involvement in control of viral gene transcription and replication. Moreover identification of R73S mutant of Vpr provides a new therapeutic avenue for controlling HIV-1 gene transcription and replication in the infected cells.


Improvement of the dermal epidermal junction in human reconstructed skin by a new c-xylopyranoside derivative.
Skin aging entails drastic changes in the extracellular dermal matrix (ECM) and dermal-epidermal junction (DEJ). These biological alterations are reflected in the clinical signs of aged skin. A new C-xylopyranoside derivative, C-beta-D-xylopyranoside-2-hydroxy-propane (C-Xyloside) has been shown to induce neo-synthesis of matrix proteins such as glycosaminoglycans and heparan sulfate proteoglycans. The aim of this study was to assess the effects of C-Xyloside on markers of the dermal epidermal junction. Basement membrane components, collagen IV, collagen VII and laminin 5 as well as sub-epidermal dermal markers, pro-collagen I and fibrillin 1 were analysed using immunohistochemistry in a reconstructed skin model, including a dermal equivalent populated with living fibroblasts. Levels of mRNA of collagen VII alpha1 and collagen IV alpha1 were evaluated in dermal fibroblasts using RT-PCR. The results showed that C-Xyloside significantly induced a higher deposition of basement membrane and DEJ proteins in the reconstructed skin model and increased collagen VII gene expression. These findings indicate that, in addition to stimulating glycosaminoglycan and heparan sulfate proteoglycan expression, C-Xyloside improves the morphogenesis of the whole DEJ, and strongly suggests beneficial effects in aged skin from restoring DEJ integrity.


Skp2 is oncogenic and overexpressed in human cancers.
Skp2 is a member of the F-box family of substrate-recognition subunits of SCF ubiquitin-protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G(1) progression, including the cyclin-dependent kinase inhibitor p27, a dosage-dependent tumor suppressor protein. In this study, we examined Skp2 and p27 protein expression by immunohistochemistry in normal oral epithelium and in different stages of malignant oral cancer progression, including dysplasia and oral squamous cell carcinoma. We found that increased levels of Skp2 protein are associated with reduced p27 in a subset of oral epithelial dysplasias and carcinomas compared with normal epithelial controls. Tumors with high Skp2 (>20% positive cells) expression invariably showed reduced or absent p27 and tumors with high p27 (>20% positive cells) expression rarely showed Skp2 positivity. Increased Skp2 protein levels were not always correlated with increased cell proliferation (assayed by Ki-67 staining), suggesting that alterations of Skp2 may contribute to the malignant phenotype without affecting proliferation. Skp2 protein overexpression may lead to accelerated p27 proteolysis and contribute to malignant progression from dysplasia to oral epithelial carcinoma. Moreover, we also demonstrate that Skp2 has oncogenic potential by showing that Skp2 cooperates with H-Ras(G12V) to malignantly transform primary rodent fibroblasts as scored by colony formation in soft agar and tumor formation in nude mice. The observations that Skp2 can mediate transformation and is up-regulated during oral epithelial carcinogenesis support a role for Skp2 as a protooncogene in human tumors.


The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Global population increases and climate change underscore the need for better comprehension of how plants acquire and process nutrients such as iron. Using cell type-specific transcriptional profiling, we identified a pericycle-specific iron deficiency response and a bHLH transcription factor, POPEYE (PYE), that may play an important role in this response. Functional analysis of PYE suggests that it positively regulates growth and development under iron-deficient conditions. Chromatin immunoprecipitation-on-chip analysis and transcriptional profiling reveal that PYE helps maintain iron homeostasis by regulating the expression of known iron homeostasis genes and other genes involved in transcription, development, and stress response. PYE interacts with PYE homologs, including IAA-Leu Resistant3 (ILR3), another bHLH transcription factor that is involved in metal ion homeostasis. Moreover, ILR3 interacts with a third protein, BRUTUS (BTS), a putative E3 ligase protein, with metal ion binding and DNA binding domains, which negatively regulates the response to iron deficiency. PYE and BTS expression is also tightly coregulated. We propose that interactions among PYE, PYE homologs, and BTS are important for maintaining iron homeostasis under low iron conditions.


Evolutionary Musicology Meets Embodied Cognition: Biocultural Coevolution and the Enactive Origins of Human Musicality.
Despite evolutionary musicology's interdisciplinary nature, and the diverse methods it employs, the field has nevertheless tended to divide into two main positions. Some argue that music should be understood as a naturally selected adaptation, while others claim that music is a product of culture with little or no relevance for the survival of the species. We review these arguments, suggesting that while interesting and well-reasoned positions have been offered on both sides of the debate, the nature-or-culture (or adaptation vs. non-adaptation) assumptions that have traditionally driven the discussion have resulted in a problematic either/or dichotomy. We then consider an alternative "biocultural" proposal that appears to offer a way forward. As we discuss, this approach draws on a range of research in theoretical biology, archeology, neuroscience, embodied and ecological cognition, and dynamical systems theory (DST), positing a more integrated model that sees biological and cultural dimensions as aspects of the same evolving system. Following this, we outline the enactive approach to cognition, discussing the ways it aligns with the biocultural perspective. Put simply, the enactive approach posits a deep continuity between mind and life, where cognitive processes are explored in terms of how self-organizing living systems enact relationships with the environment that are relevant to their survival and well-being. It highlights the embodied and ecologically situated nature of living agents, as well as the active role they play in their own developmental processes. Importantly, the enactive approach sees cognitive and evolutionary processes as driven by a range of interacting factors, including the socio-cultural forms of activity that characterize the lives of more complex creatures such as ourselves. We offer some suggestions for how this approach might enhance and extend the biocultural model. To conclude we briefly consider the implications of this approach for practical areas such as music education.


Association Between PD-L1 and Histatin1, 3 Expression in Advanced Head and Neck Squamous Cell Carcinoma.
The prognosis of advanced stage head and neck squamous cell carcinoma (HNSCC) has remained unimproved for the past decades. Therefore, novel diagnostic markers and treatment options are required. Recently, an inhibitor for immune checkpoint program death ligand-1 (PD-L1), was approved by the FDA, and used in HNSCC patients. Histatins (HTNs), one of the common antimicrobial peptides in saliva, have demonstrated wound healing and antifungal capabilities and other functions on the oral epithelium. Dysregulation of HTN1 and HTN3 has also been reported in HNSCC through genomic and proteomic studies. This study aimed to investigate the association between histatins (HTN1 and HTN3) and PD-L1 in advanced HNSCC. Data of gene expression in HNSCC were collected from TCGA and analyzed using a data-mining platform website (https://ualcan.path.uab.edu/). Tissue microarrays containing 98 samples of HNSCC patients and non-neoplastic controls were immunolabeled against PD-L1, HTN1, and HTN3. The immunohistochemistry results were quantified using ImageJ. The expression of PD-L1 and HTN1 was significantly higher in tumors than normal tissues (p<0.001), but no significant difference was found regarding HTN3. Metastatic HNSCC samples exhibited significantly higher expression of PD-L1 (p<0.018), compared to the non-metastatic group. Association between HTN1 and HTN3 was found using Pearson correlation coefficient (r=0.603, p<0.001). No overall survival difference was evident among our samples. PD-L1 and HTN1 are associated with the progression of HNSCC. PD-L1 expression correlated with that of HTN3.


P50, N100, and P200 sensory gating: relationships with behavioral inhibition, attention, and working memory.
P50, N100, and P200 auditory sensory gating could reflect mechanisms involved in protecting higher-order cognitive functions, suggesting relationships between sensory gating and cognition. This hypothesis was tested in 56 healthy adults who were administered the paired-click paradigm and two adaptations of the continuous performance test (Immediate/Delayed Memory Task, IMT/DMT). Stronger P50 gating correlated with fewer commission errors and prolonged reaction times on the DMT. Stronger N100 and P200 gating correlated with better discriminability on the DMT. Finally, prolonged P200 latency related to better discriminability on the IMT. These findings suggest that P50, N100, and P200 gating could be involved in protecting cognition by affecting response bias, behavioral inhibition, working memory, or attention.


Staphylococcus aureus biofilms decrease osteoblast viability, inhibits osteogenic differentiation, and increases bone resorption in vitro.
Osteomyelitis is a severe and often debilitating disease characterized by inflammatory destruction of bone. Despite treatment, chronic infection often develops which is associated with increased rates of treatment failure, delayed osseous-union, and extremity amputation. Within affected bone, bacteria exist as biofilms, however the impact of biofilms on osteoblasts during disease are unknown. Herein, we evaluated the effect of S. aureus biofilms on osteoblast viability, osteogenic potential, and the expression of the pro-osteoclast factor, receptor activator of NF-kB ligand (RANK-L). Osteoblasts were exposed to biofilm conditioned media (BCM) from clinical wound isolates of Staphylococcus aureus under normal growth and osteogenic conditions to assess cellular viability and osteoblast differentiation, respectively. Cell viability was evaluated using a live/dead assay and by quantifying total cellular DNA at days 0, 1, 3, 5, and 7. Apoptosis following treatment with BCM was measured by flow-cytometry using the annexin V-FITC/PI apoptosis kit. Osteogenic differentiation was assessed by measuring alkaline phosphatase activity and intracellular accumulation of calcium and osteocalcin for up to 21 days following exposure to BCM. Expression of genes involved in osteogenic differentiation and osteoclast regulation, were also evaluated by quantitative real-time PCR. BCM from clinical strains of S. aureus reduced osteoblast viability which was accompanied by an increase in apoptosis. Osteogenic differentiation was significantly inhibited following treatment with BCM as indicated by decreased alkaline phosphatase activity, decreased intracellular accumulation of calcium and inorganic phosphate, as well as reduced expression of transcription factors and genes involved in bone mineralization in viable cells. Importantly, exposure of osteoblasts to BCM resulted in up-regulated expression of RANK-L and increase in the RANK-L/OPG ratio compared to the untreated controls. Together these studies suggest that soluble factors produced by S. aureus biofilms may contribute to bone loss during chronic osteomyelitis simultaneously by: (1) reducing osteoblast viability and osteogenic potential thereby limiting new bone growth and (2) promoting bone resorption through increased expression of RANK-L by osteoblasts. To our knowledge these are the first studies to demonstrate the impact of staphylococcal biofilms on osteoblast function, and provide an enhanced understanding of the pathogenic role of staphylococcal biofilms during osteomyelitis.


Taurine and the renal system.
Taurine participates in a number of different physiologic and biologic processes in the kidney, often reflected by urinary excretion patterns. The kidney is key to aspects of taurine body pool size and homeostasis. This review will examine the renal-taurine interactions relative to ion reabsorption; renal blood flow and renal vascular endothelial function; antioxidant properties, especially in the glomerulus; and the role of taurine in ischemia and reperfusion injury. In addition, taurine plays a role in the renal cell cycle and apoptosis, and functions as an osmolyte during the stress response. The role of the kidney in adaptation to variations in dietary taurine intake and the regulation of taurine body pool size are described. Finally, the protective function of taurine against several kidney diseases is reviewed.


Getting in synch: Unpacking the role of parent-child synchrony in the development of internalizing and externalizing behaviors.
While substantial research supports the role of parent-child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent-child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent-child dyads first came to the laboratory when the child was 4-5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child's internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent-child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent-child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent-child dyad's ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors.


Automatic Diagnosis of High-Resolution Esophageal Manometry Using Artificial Intelligence.
High-resolution esophageal manometry (HREM) is the gold standard procedure used for the diagnosis of esophageal motility disorders (EMD). Artificial intelligence (AI) might provide an efficient solution for the automatic diagnosis of EMD by improving the subjective interpretation of HREM images. The aim of our study was to develop an AI-based system, using neural networks, for the automatic diagnosis of HREM images, based on one wet swallow raw image. In the first phase of the study, the manometry recordings of our patients were retrospectively analyzed by three experienced gastroenterologists, to verify and confirm the correct diagnosis. In the second phase of the study raw images were used to train an artificial neural network. We selected only those tracings with ten test swallows that were available for analysis, including a total of 1570 images. We had 10 diagnosis categories, as follows: normal, type I achalasia, type II achalasia, type III achalasia, esophago-gastric junction outflow obstruction, jackhammer oesophagus, absent contractility, distal esophageal spasm, ineffective esophageal motility, and fragmented peristalsis, based on Chicago classification v3.0 for EMDs. The raw images were cropped, binarized, and automatically divided in 3 parts: training, testing, validation. We used Inception V3 CNN model, pre-trained on ImageNet. We developed a custom classification layer, that allowed the CNN to classify each wet swallow image from the HREM system into one of the diagnosis categories mentioned above. Our algorithm was highly accurate, with an overall precision of more than 93%. Our neural network approach using HREM images resulted in a high accuracy automatic diagnosis of EMDs.


Genetic validation of the protein arginine methyltransferase PRMT5 as a candidate therapeutic target in glioblastoma.
Glioblastoma is the most common and aggressive histologic subtype of brain cancer with poor outcomes and limited treatment options. Here, we report the selective overexpression of the protein arginine methyltransferase PRMT5 as a novel candidate theranostic target in this disease. PRMT5 silences the transcription of regulatory genes by catalyzing symmetric dimethylation of arginine residues on histone tails. PRMT5 overexpression in patient-derived primary tumors and cell lines correlated with cell line growth rate and inversely with overall patient survival. Genetic attenuation of PRMT5 led to cell-cycle arrest, apoptosis, and loss of cell migratory activity. Cell death was p53-independent but caspase-dependent and enhanced with temozolomide, a chemotherapeutic agent used as a present standard of care. Global gene profiling and chromatin immunoprecipitation identified the tumor suppressor ST7 as a key gene silenced by PRMT5. Diminished ST7 expression was associated with reduced patient survival. PRMT5 attenuation limited PRMT5 recruitment to the ST7 promoter, led to restored expression of ST7 and cell growth inhibition. Finally, PRMT5 attenuation enhanced glioblastoma cell survival in a mouse xenograft model of aggressive glioblastoma. Together, our findings defined PRMT5 as a candidate prognostic factor and therapeutic target in glioblastoma, offering a preclinical justification for targeting PRMT5-driven oncogenic pathways in this deadly disease.


Jejunum free flap in hypopharynx reconstruction: case series.
Surgical treatment of hypopharyngeal cancers with extension to the retrocricoid region generally requires a circumferential pharyngolaryngectomy followed by a reconstruction of the removed segment of the upper digestive tract. Historically, many techniques have been used in order to achieve a safe and functional reconstruction. Jejunum interposition is generally considered the best reconstructive technique. This study examines the details of the surgical technique, the complications, the oncological and the functional results in a series of 29 consecutive patients submitted to circumferential pharyngoesophageal resection for advanced hypopharyngeal cancer followed by reconstruction with a free flap of jejunum. Three of the transplants failed because of venous thrombosis. The overall success rate was 90%. There were no general complications. A good swallowing has been preserved in all our patients. All our patients where a phonatory prosthesis was positioned (20/29) were able to achieve speech following speech therapy and all were satisfied with their own capacity to communicate. The prognosis of hypopharyngeal tumours (18-40% at 5 years) remains poor, but jejunum autografts are being shown to be an excellent choice for the reconstruction of the cervical hypopharyngo-oesophagus offering the patient fast rehabilitation and a reasonable quality of survival. Our experience confirm that this kind of reconstruction is safe with a good results in improving oncologic controls and restoring a good quality of life.


Progress in centralised ethics review processes: Implications for multi-site health evaluations.
Increasingly, public sector programmes respond to complex social problems that intersect specific fields and individual disciplines. Such responses result in multi-site initiatives that can span nations, jurisdictions, sectors and organisations. The rigorous evaluation of public sector programmes is now a baseline expectation. For evaluations of large and complex multi-site programme initiatives, the processes of ethics review can present a significant challenge. However in recent years, there have been new developments in centralised ethics review processes in many nations. This paper provides the case study of an evaluation of a national, inter-jurisdictional, cross-sector, aged care health initiative and its encounters with Australian centralised ethics review processes. Specifically, the paper considers progress against the key themes of a previous five-year, five nation study (Fitzgerald and Phillips, 2006), which found that centralised ethics review processes would save time, money and effort, as well as contribute to more equitable workloads for researchers and evaluators. The paper concludes with insights for those charged with refining centralised ethics review processes, as well as recommendations for future evaluators of complex multi-site programme initiatives.


The impact of mass media interventions on tuberculosis awareness, health-seeking behaviour and health service utilisation: a systematic review protocol.
Tuberculosis (TB) is a serious public health problem in many parts of the world. Strategies to curb the spread of TB must match the multifaceted nature of the epidemic. The use of mass media is one of the important strategies in communicating behavioural change in relation to TB prevention and the treatment. However, the benefits of this intervention are unclear. We, therefore, plan to conduct a systematic review on the effects of mass media interventions on TB awareness, health-seeking behaviour and health service utilisation. We will preferably include randomised controlled trials (RCTs) in this systematic review. However, non-randomised studies will be included if there is an inadequate number of RCTs. We will perform electronic searches in PubMed, Scopus and other databases, along with manual searches. Articles written (or translated) in English and French and published between 1 January 1980 and 31 October 2013 will be eligible for inclusion in this review. The primary outcomes will be TB knowledge, attitudes and awareness, healthcare-seeking behaviour and service utilisation. The secondary outcomes will include stigma and discrimination against people with TB and the costs of the interventions. We will investigate clinical and statistical heterogeneity and pool studies judged to be clinically and statistically homogeneous. Relative risks will be calculated for dichotomous outcomes and mean differences for continuous outcomes, both with their corresponding 95% CIs. The systematic review will use data that is not linked to individuals. The review findings may have implications for clinical practice and future research, and will be disseminated electronically and in print through peer-reviewed publications. PROSPERO CRD42013005867.


Is minimally invasive surgery less invasive in total hip replacement? A pilot study.
It has been suggested that minimally invasive surgery (MIS) in total hip replacement (THR) is less traumatic than standard techniques. This study was designed to address the question of whether an anterior MIS approach generates less inflammation and muscle damage than the standard posterolateral (PL) approach. Inflammation parameters such as interleukin-6 (IL-6), muscle damage parameters like heart type fatty acid binding protein (H-FABP), and haemoglobin (Hb) levels were determined pre-operatively and at five consecutive points post-operatively in 10 patients operated through a MIS anterior approach and in 10 patients operated through a PL approach. The mean IL-6 concentration increased from 3 pg/ml in both groups pre-operatively to 78.5 pg/ml (PL group) vs 74.8 pg/ml (MIS group) at 6 hours post-operatively and reached a maximum of 100 pg/ml (PL group) vs 90.5 pg/ml pg/ml (MIS group) after 24 hours. Up to this time point, there was a decrease in both groups. The post-operative mean H-FABP concentration increased to 10.7 microg/l in the PL group vs 15.8 microg/l in the MIS group. It formed a plateau and decreased after 24 hours post-operatively. The Hb levels were 14.5 g/dl before surgery and decreased to 10.7 g/dl (PL group) and 10.0 g/dl (MIS group) at 72 hours post-operatively. No significant differences were found between the two approaches either in inflammation and muscle damage or blood loss. Although the absence of a learning curve may explain the lack of a difference between both techniques, we speculate that the term MIS is at least doubtful in terms of being less traumatic.


Strategies to improve antibiotic access and a way forward for lower middle-income countries.
Antibiotics have substantially improved life expectancy in past decades through direct control or prevention of infections. However, emerging antibiotic resistance and lack of access to effective antibiotics have significantly increased the death toll from infectious diseases, making it one of the biggest threats to global health. Addressing the antibiotic crisis to meet future needs require considerable investment in both research and development along with ensuring a viable marketplace to encourage innovation. Fortunately, there has been some improvement in the number of antibiotics approved or in different phases of development through collective global efforts. However, the universal access to these essential novel and generic antibiotics, especially in low- and middle-income countries (LMICs), is challenged by poor economic incentives, regulatory hurdles and poor health infrastructure. Recently, the agenda of securing and expanding access has gained global attention. Several mechanisms are now being proposed and implemented to improve access to essential antibiotics. This review provides an insight into the major barriers to antibiotic access as well as the models proposed and implemented to mitigate accessibility issues. These models include but are not limited to market entry rewards, subscription models and transferable exclusivity vouchers. Further, global access programmes including, Global Antibiotic Research and Development Partnership, Antimicrobial Resistance Action Fund and SECURE Platform are discussed. We also propose the way forward for improving access in LMICs with suggested measures to improve access to generic and novel antibiotics.


Withdrawn: Supramolecular Evolution of Protein Organization.
Ahead of Print article withheld by publisher: It has come to the publisher's attention that some key concepts reviewed in the manuscript entitled "Supramolecular Evolution of Protein Organization" by Ariel Fernández (scheduled to appear in Volume 47 of the Annual Review of Genetics) derive from at least one article in the primary research literature currently under dispute due to unsettled anomalies in the data and/or interpretation. Annual Reviews, with concurrence of the review's author, has decided to withhold final publication pending satisfactory resolution.


Development of a ReaxFF reactive force field for tetrabutylphosphonium glycinate/CO2 mixtures.
Carbon dioxide interacts with the ionic liquid tetrabutylphosphonium glycinate, [P(C4)4][Gly], through both physical and chemical absorption. We present a parametrization of the ReaxFF force field for this system that accounts for both chemical and physical interactions. The parametrization was developed from an extensive training set including periodic density functional theory (DFT) calculations of reaction pathways between CO2 and the anion [Gly](-) in the condensed phase, condensed-phase molecular dynamics (MD) configurations, gas-phase CO2-anion and CO2-cation interactions, and gas-phase cluster calculations for intra-ion interactions. The optimized ReaxFF parameters capture the essential features of both physical and chemical interactions between CO2 and [P(C4)4][Gly] as compared with experiments, van der Waals-corrected DFT calculations, or, in the case of physical interactions, classical force field calculations. The probability distributions of the distance between C (from CO2) and N (from the anion) and the CO2 bend angles calculated from MD simulations with the optimized ReaxFF force field are in good general agreement with those from DFT-based MD simulations. We predict that the density of CO2/[P(C4)4][Gly] mixtures increases with increasing CO2 concentration up to at least 50 mol % CO2. We attribute the significant increase in density to the small effective volume occupied by chemically bound CO2 in the mixture. The predicted increase in density may be tested experimentally.


Colicins--exocellular lethal proteins of Escherichia coli.
Colicins are toxic exoproteins produced by bacteria of colicinogenic strains of Escherichia coli and some related species of Enterobacteriaceae, during the growth of their cultures. They inhibit sensitive bacteria of the same family. About 35% E. coli strains appearing in human intestinal tract are colicinogenic. Synthesis of colicins is coded by genes located on Col plasmids. Until now more than 34 types of colicins have been described, 21 of them in greater detail, viz. colicins A, B, D, E1-E9, Ia, Ib, JS, K, M, N, U, 5, 10. In general, their interaction with sensitive bacteria includes three steps: (1) binding of the colicin molecule to a specific receptor in the bacterial outer membrane; (2) its translocation through the cell envelope; and (3) its lethal interaction with the specific molecular target in the cell. The classification of colicins is based on differences in the molecular events of these three steps.


Relapse rate and outcome of ANCA-associated small vessel vasculitis after transplantation.
Anti-neutrophil cytoplasm antibody-associated systemic vasculitis (AASV) is a rare disease and frequently leads to end-stage renal disease (ESRD). Potentially fatal disease activity can develop after the onset of ESRD or in transplanted patients despite the immunosuppressive effects of uraemia and rejection prophylaxis, respectively, leading to concern that such patients may have greater morbidity and mortality. To assess the outcome of patients with AASV following kidney transplantation, a retrospective analysis was performed of nine patients with AASV at our unit who received renal transplants between 1987 and 2000. The renal survival of the patients was compared with a control population who received kidney transplants over the same period for causes other than AASV and diabetes mellitus. Nine patients with the diagnosis of AASV (five patients with Wegener's granulomatosis and four with microscopic polyangiitis) received eight cadaveric grafts and one live-related graft after a mean of 44 months from the start of dialysis. These patients had a mean age of 49.2 years at time of transplantation and they were followed up for a mean of 62 months post-transplantation. Two patients with Wegener's granulomatosis suffered a vasculitic relapse affecting the upper respiratory tract at 40 and 50 months post-transplantation, corresponding to a relapse rate of 0.04 per patient per year. The renal transplant function of vasculitis patients compared with 18 non-diabetic control patients who were transplanted at the same time was better in the vasculitis patients at some time points (P=0.054 at 6 months). There is a substantial relapse rate in the AASV population, especially affecting the upper respiratory tract and with increasing duration of follow-up. Nonetheless, renal transplantation is a good option for the treatment of vasculitis patients and their outcome compares favourably with that of other non-diabetic patients following transplantation.


[Leeching in the treatment of chronic inflammatory and dystrophic diseases of the salivary glands].
Twenty patients with chronic inflammatory and dystrophic diseases of the salivary glands (sialadenitis, sialadenosis) were examined and treated using hirudotherapy. Positive clinical shifts were observed in 50% patients; the most pronounced therapeutic effect was observed in patients with sialadenosis. Hirudotherapy was ineffective in patients with chronic parenchymatous parotitis paralleled by Sjogren's syndrome.


Extracellular Vesicles as Therapeutics for Brain Injury and Disease.
Extracellular vesicles (EVs) are gaining tremendous importance in comprehending central nervous system (CNS) function and treating neurological disorders because of their role in intercellular communication and reparative processes, and suitability as drug delivery vehicles. Since EVs have lipid membranes, they cross the blood-brain barrier easily and communicate with target neurons and glia even deep inside the brain. EVs from various sources have been isolated, characterized, and tailored for promoting beneficial effects in conditions, such as brain injury and disease. Particularly, EVs isolated from mesenchymal stem cells and neural stem cells have shown promise for alleviating brain dysfunction after injury or disease. Such properties of stem cell-derived EVs have great importance for clinical applications, as EV therapy can avoid several concerns typically associated with cell therapy. This minireview confers the competence of EVs for improving brain function by modulating CNS injury and disease.


Simulation, situated conceptualization, and prediction.
Based on accumulating evidence, simulation appears to be a basic computational mechanism in the brain that supports a broad spectrum of processes from perception to social cognition. Further evidence suggests that simulation is typically situated, with the situated character of experience in the environment being reflected in the situated character of the representations that underlie simulation. A basic architecture is sketched of how the brain implements situated simulation. Within this framework, simulators implement the concepts that underlie knowledge, and situated conceptualizations capture patterns of multi-modal simulation associated with frequently experienced situations. A pattern completion inference mechanism uses current perception to activate situated conceptualizations that produce predictions via simulations on relevant modalities. Empirical findings from perception, action, working memory, conceptual processing, language and social cognition illustrate how this framework produces the extensive prediction that characterizes natural intelligence.


Thioredoxin is required for vacuole inheritance in Saccharomyces cerevisiae.
The vacuole of Saccharomyces cerevisiae projects a stream of tubules a and vesicles (a "segregation structure") into the bud in early S phase. We have described an in vitro reaction, requiring physiological temperature, ATP, and cytosol, in which isolated vacuoles form segregation structures and fuse. This in vitro reaction is defective when reaction components are prepared from vac mutants that are defective in this process in vivo, Fractionation of the cytosol reveals at least three components, each of which can support the vacuole fusion reaction, and two stimulatory fractions. Purification of one "low molecular weight activity" (LMA1) yields a heterodimeric protein with a thioredoxin subunit. Most of the thioredoxin of yeast is in this complex rather than the well-studied monomer. A deletion of both S. cerevisiae thioredoxin genes causes a striking vacuole inheritance defect in vivo, establishing a role for thioredoxin as a novel factor in this trafficking reaction.


Use of a Bayesian algorithm in the computer-assisted diagnosis of appendicitis.
One hundred consecutive patients with acute right lower quadrant abdominal pain were prospectively evaluated with a computerized Bayesian diagnostic algorithm. An accuracy rate of 92 per cent was obtained. Computer recommendations would have resulted in a negative exploration rate of 9 per cent, as compared with the rate of 19 per cent which was actually obtained. Even though our clinical management of these patients was in keeping with accepted standards, the Bayesian program would have avoided eight unnecessary operations. In all instances in which the patient presented with appendicitis, the computer correctly predicted that appendicitis was present. Computer-assisted diagnostic programs using a Bayesian approach may have some role in the evaluation of right lower quadrant abdominal pain. The technique presented herein describes a means of developing a database of conditional probabilities without reliance on large patient surveys. Even with this refinement, the Bayesian approach to diagnosis remains complex. The development of this type of program requires close interaction between computer scientists and surgeons. Nevertheless, the approach does appear promising and it may well be worth the considerable effort required to initiate such a system. The exact role for Bayesian diagnostic analysis cannot be predicted at this point. Certainly it should have no greater importance than a routine laboratory test. Perhaps the results of Bayesian analysis in this setting might assume a diagnostic significance similar to that of the white blood cell count. The work of DeDombal has done much to eliminate the physician reluctance seen with earlier programs. It has become increasingly apparent that computers may perform many clinically useful functions without infringing upon the art of medicine. The computer assisted diagnosis of acute abdominal pain may well constitute one such function.


Robust Iris-Localization Algorithm in Non-Cooperative Environments Based on the Improved YOLO v4 Model.
Iris localization in non-cooperative environments is challenging and essential for accurate iris recognition. Motivated by the traditional iris-localization algorithm and the robustness of the YOLO model, we propose a novel iris-localization algorithm. First, we design a novel iris detector with a modified you only look once v4 (YOLO v4) model. We can approximate the position of the pupil center. Then, we use a modified integro-differential operator to precisely locate the iris inner and outer boundaries. Experiment results show that iris-detection accuracy can reach 99.83% with this modified YOLO v4 model, which is higher than that of a traditional YOLO v4 model. The accuracy in locating the inner and outer boundary of the iris without glasses can reach 97.72% at a short distance and 98.32% at a long distance. The locating accuracy with glasses can obtained at 93.91% and 84%, respectively. It is much higher than the traditional Daugman's algorithm. Extensive experiments conducted on multiple datasets demonstrate the effectiveness and robustness of our method for iris localization in non-cooperative environments.


Hemostatic changes in thyroid diseases: haemostasis and thrombosis.
Several studies have reported hemostatic abnormalities, both in terms of bleeding or thrombosis, in patients with various thyroid dysfunctions. The aim of this review is to briefly discuss the relationship between thyroid disorders and hemostasis (i.e. primary hemostasis, coagulation factors and fibrinolytic system). From the analysis of the more recent literature data, it appears evident that most of the coagulation abnormalities associated with thyroid disorders are a consequence of a direct action of thyroid hormones on the synthesis of various hemostatic factors or a derangement of immune function. On the whole, these data suggest that a hypercoagulable state is present in hyperthyroid patients, while patients suffering from moderate hypothyroidism are at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism.


[Intraocular fibrosis after perforating injury of the posterior segment. Experimental study].
Double perforating injuries and linear wounds were produced in the posterior segment of the rabbit eye in order to study post-traumatic intraocular proliferation. After observation for one month, the animals were sacrificed and the eyes treated for histologic examination. Transvitreous strands and preretinal membranes slowly developed, sometimes inducing traction retinal detachment. Histologic studies demonstrated the new-formed tissue to be fibrovascular, mainly containing collagenous fibers and fibroblast-like cells. This fibroblastic proliferation closed the wound through the ocular membranes and invaded the vitreous using vitreous fibers as a scaffold. The authors discuss the signification of this results comparing them to literature data on different animals and on man.


Tunable Li-ion diffusion properties in MoSSe bilayer anodes by strain gradient.
Layered MoSSe nanostructures have been shown as potential candidates for the anode of lithium ion (Li-ion) batteries. The diffusion properties are generally critical to the performance of ionic batteries. The possible migration paths and associated diffusion energy barriers of Li-ions are systematically explored in MoSSe bilayer anodes with different stacking patterns by means of first-principles simulations. It is found that the diffusion properties strongly depend on interfaces and stacking patterns. Furthermore, the simulation results show that the diffusion energy barrier (and thus the diffusion coefficient) can be significantly reduced (enlarged) by applying a positive strain gradient, while increased (reduced) by applying a negative one. For example, the diffusion coefficient is increased roughly by 100 times relative to that of the pristine one when subjected to a strain gradient of 0.02 Å-1. In particular, it is found that less maximum strain is required in the strain-gradient than the uniform strain in order to achieve the same diffusion energy barrier. By careful analysis, the underlying mechanism can be attributed to the flexo-diffusion coupling effect. The coupling strength is characterized by the so-called flexo-diffusion coupling constant which is also calculated for each simulation model. The results of this work may provide valuable insights into the design and optimization of the anodes of ionic batteries.


Flow time through esophagogastric junction derived during high-resolution impedance-manometry studies: a novel parameter for assessing esophageal bolus transit.
This study aimed to develop and validate a method to measure bolus flow time (BFT) through the esophagogastric junction (EGJ) using a high-resolution impedance-manometry (HRIM) sleeve. Ten healthy subjects were studied with concurrent HRIM and videofluoroscopy; another 15 controls were studied with HRIM alone. HRIM studies were performed using a 4.2-mm-outer diameter assembly with 36 pressure sensors at 1-cm intervals and 18 impedance segments at 2-cm intervals (Given Imaging, Los Angeles, CA). HRIM and fluoroscopic data from four barium swallows, two in the supine and two in the upright position, were analyzed to create a customized MATLAB program to calculate BFT using a HRIM sleeve comprising three sensors positioned at the crural diaphragm. Bolus transit through the EGJ measured during blinded review of fluoroscopy was almost identical to BFT calculated with the HRIM sleeve, with the nadir impedance deflection point used as the signature of bolus presence. Good correlation existed between videofluoroscopy for measurement of upper sphincter relaxation to beginning of flow [R = 0.97, P < 0.001 (supine) and R = 0.77, P < 0.01 (upright)] and time to end of flow [R = 0.95, P < 0.001 (supine) and R = 0.82, P < 0.01 (upright)]. The medians and interquartile ranges (IQR) of flow time though the EGJ in 15 healthy subjects calculated using the virtual sleeve were 3.5 s (IQR 2.3-3.9 s) in the supine position and 3.2 s (IQR 2.3-3.6 s) in the upright position. BFT is a new metric that provides important information about bolus transit through the EGJ. An assessment of BFT will determine when the EGJ is open and will also provide a useful method to accurately assess trans-EGJ pressure gradients during flow.


Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine.
The randomized, placebo-controlled, phase 3 QUAZAR AML-001 trial (ClinicalTrials.gov identifier: NCT01757535) evaluated oral azacitidine (Oral-AZA) in patients with acute myeloid leukemia (AML) in first remission after intensive chemotherapy (IC) who were not candidates for hematopoietic stem cell transplantation. Eligible patients were randomized 1:1 to Oral-AZA 300 mg or placebo for 14 days per 28-day cycle. We evaluated relapse-free survival (RFS) and overall survival (OS) in patient subgroups defined by NPM1 and FLT3 mutational status at AML diagnosis and whether survival outcomes in these subgroups were influenced by presence of post-IC measurable residual disease (MRD). Gene mutations at diagnosis were collected from patient case report forms; MRD was determined centrally by multiparameter flow cytometry. Overall, 469 of 472 randomized patients (99.4%) had available mutational data; 137 patients (29.2%) had NPM1 mutations (NPM1mut), 66 patients (14.1%) had FLT3 mutations (FLT3mut; with internal tandem duplications [ITD], tyrosine kinase domain mutations [TKDmut], or both), and 30 patients (6.4%) had NPM1mut and FLT3-ITD at diagnosis. Among patients with NPM1mut, OS and RFS were improved with Oral-AZA by 37% (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.98) and 45% (HR, 0.55; 95% CI, 0.35-0.84), respectively, vs placebo. Median OS was improved numerically with Oral-AZA among patients with NPM1mut whether without MRD (48.6 months vs 31.4 months with placebo) or with MRD (46.1 months vs 10.0 months with placebo) post-IC. Among patients with FLT3mut, Oral-AZA improved OS and RFS by 37% (HR, 0.63; 95% CI, 0.35-1.12) and 49% (HR, 0.51; 95% CI, 0.27-0.95), respectively, vs placebo. Median OS with Oral-AZA vs placebo was 28.2 months vs 16.2 months, respectively, for patients with FLT3mut and without MRD and 24.0 months vs 8.0 months for patients with FLT3mut and MRD. In multivariate analyses, Oral-AZA significantly improved survival independent of NPM1 or FLT3 mutational status, cytogenetic risk, or post-IC MRD status.


What is the value and impact of quality and safety teams? A scoping review.
The purpose of this study was to conduct a scoping review of the literature about the establishment and impact of quality and safety team initiatives in acute care. Studies were identified through electronic searches of Medline, Embase, CINAHL, PsycINFO, ABI Inform, Cochrane databases. Grey literature and bibliographies were also searched. Qualitative or quantitative studies that occurred in acute care, describing how quality and safety teams were established or implemented, the impact of teams, or the barriers and/or facilitators of teams were included. Two reviewers independently extracted data on study design, sample, interventions, and outcomes. Quality assessment of full text articles was done independently by two reviewers. Studies were categorized according to dimensions of quality. Of 6,674 articles identified, 99 were included in the study. The heterogeneity of studies and results reported precluded quantitative data analyses. Findings revealed limited information about attributes of successful and unsuccessful team initiatives, barriers and facilitators to team initiatives, unique or combined contribution of selected interventions, or how to effectively establish these teams. Not unlike systematic reviews of quality improvement collaboratives, this broad review revealed that while teams reported a number of positive results, there are many methodological issues. This study is unique in utilizing traditional quality assessment and more novel methods of quality assessment and reporting of results (SQUIRE) to appraise studies. Rigorous design, evaluation, and reporting of quality and safety team initiatives are required.


Response Time as an Implicit Self-Schema Indicator for Depression Among Undergraduate Students: Preliminary Findings From a Mobile App-Based Depression Assessment.
Response times to depressive symptom items in a mobile-based depression screening instrument has potential as an implicit self-schema indicator for depression but has yet to be determined; the instrument was designed to readily record depressive symptoms experienced on a daily basis. In this study, the well-validated Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (K-CESD-R) was adopted. The purpose of this study was to investigate the relationship between depression severity (ie, explicit measure: total K-CESD-R Mobile scores) and the latent trait of interest in schematic self-referent processing of depressive symptom items (ie, implicit measure: response times to items in the K-CESD-R Mobile scale). The purpose was to investigate this relationship among undergraduate students who had never been diagnosed with, but were at risk for, major depressive disorder (MDD) or comorbid MDD with other neurological or psychiatric disorders. A total of 70 participants-36 males (51%) and 34 females (49%)-aged 19-29 years (mean 22.66, SD 2.11), were asked to complete both mobile and standard K-CESD-R assessments via their own mobile phones. The mobile K-CESD-R sessions (binary scale: yes or no) were administered on a daily basis for 2 weeks. The standard K-CESD-R assessment (5-point scale) was administered on the final day of the 2-week study period; the assessment was delivered via text message, including a link to the survey, directly to participants' mobile phones. A total of 5 participants were excluded from data analysis. The result of polynomial regression analysis showed that the relationship between total K-CESD-R Mobile scores and the reaction times to the depressive symptom items was better explained by a quadratic trend-F (2, 62)=21.16, P<.001, R2=.41-than by a linear trend-F (1, 63)=25.43, P<.001, R2=.29. It was further revealed that the K-CESD-R Mobile app had excellent internal consistency (Cronbach alpha=.94); at least moderate concurrent validity with other depression scales, such as the Korean version of the Quick Inventory for Depressive Symptomatology-Self Report (ρ=.38, P=.002) and the Patient Health Questionnaire-9 (ρ=.48, P<.001); a high adherence rate for all participants (65/70, 93%); and a high follow-up rate for 10 participants whose mobile or standard K-CESD-R score was 13 or greater (8/10, 80%). As hypothesized, based on a self-schema model for depression that represented both item and person characteristics, the inverted U-shaped relationship between the explicit and implicit self-schema measures for depression showed the potential of an organizational breakdown; this also showed the potential for a subsequent return to efficient processing of schema-consistent information along a continuum, ranging from nondepression through mild depression to severe depression. Further, it is expected that the updated K-CESD-R Mobile app can play an important role in encouraging people at risk for depression to seek professional follow-up for mental health care.


Influence of fatness, intelligence, education and sociodemographic factors on response rate in a health survey.
The aim was to investigate the characteristics of non-responders to an invitation to attend a health examination. Taking advantage of an ongoing study of obesity, this was a survey of a cohort of severely obese men, with a randomly selected control group. The participants were draftees to the compulsory Danish military draft board examination between 1943 and 1977. Among 362,200 draftees, 1940 were identified as severely obese (body mass index greater than or equal to 31 kg/m2). A comparison group of 1801 subjects was randomly drawn from the remaining population. During the period 1981-3 those still alive and living in the same region (1651 obese, 1504 control) were invited to a health examination. The examination was attended by 964 obese (58%) and 1134 controls (75%). In both groups an increasing response rate was associated with decreasing body mass index, and increasing intelligence test score, educational level, current social class, age (up to 50 years) and proximity of residence. Logistic regression analysis showed that all these variables had independent effects on response rate. Frequency and duration of hospital admissions during the period 1977-82 did not differ among responders and non-responders in either group. Response rates in health surveys are strongly influenced by degree of fatness, intelligence, educational level, social class, age, and proximity of residence.


Mechanism of Hepatitis B Virus cccDNA Formation.
Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.


Tailoring the plasmon-induced transparency resonances in terahertz metamaterials.
We experimentally demonstrate that a coupled metamaterial composed of sub-wavelength split-ring-resonators (SRRs) and closed-ring-resonators (CRRs) can tailor the plasmon-induced-transparency (PIT) resonances when the external electric field is parallel to the gaps of SRRs. Rotating or moving SRRs in vertical direction plays a critical role in the EIT functionality, while an excellent robust performance can be acquired via moving SRRs in the horizontal direction. Based on the results, a polarization-independent and polarization-dependent planar metamaterial are designed, fabricated and measured. In contrast to the spectral property of the polarization-independent medium, the polarization-dependent one is featured by isolated PIT phenomena in the frequency-domain, with respect to the horizontal and vertical polarized incident beam. Transmission responses of the PIT metamaterial are characterized with terahertz time-domain spectroscopy, showing a good agreement with the rigorous numerical simulation results. The presented work delivers a unique way to excite and modulate the PIT response, toward developing polarization-independent and polarization-dependent slow-light building blocks, ultrasensitive sensors and narrow-band filters functioning in the THz regime.


Determinants of neonatal mortality in the largest international border of Brazil: a case-control study.
Foz do Iguassu is a Brazilian municipality located in the most populous international border of the country and provides medical care to foreigners. Neonatal mortality in the city is higher than Brazil's average and corresponds to 61% of all deaths in children under five. The current study aimed to identify the determinants of neonatal mortality in Foz do Iguassu. In this case-control study, we analyzed all neonatal deaths occurred in Foz do Iguassu from 2012 to 2016. Birth and mortality data were extracted from two national governmental databases (SINASC and SIM). We extracted data on (i) maternal sociodemographic characteristics, (ii) pregnancy care, and (iii) newborn characteristics. Multiple logistic regression with the conceptual framework was applied to examine the factors associated with neonatal mortality. Most of the deaths occurred in the early neonatal period (65.9%). The factors associated with neonatal death were fetal congenital anomaly (OR 22.49; CI 95% 7.44-67.95; p = < 0.001); low birth weight (OR 17.15; CI 95% 8.56-34.37; p = < 0.001), first minute Apgar score under 7 (OR 15.60; CI 95% 8.23-29.67; p = < 0.001); zero to 3 prenatal appointments (OR 3.34; CI 95% 1.28-8.73; p = 0.014) and prematurity (OR 3.60; CI 95% 1.87-7.11; p = < 0.001). The high rate of neonatal death in Foz do Iguassu is strongly associated with newborn characteristics and not associated with maternal sociodemographic characteristics. Thus, the health services in the Brazilian side of this international borders should be aware of the quality of the prenatal care and childbirth attention provided.


Neck computed tomography in pediatric neck mass as initial evaluation in ED: is it malpractice?
Although ultrasound is regarded as the first choice imaging modality for evaluating a pediatric neck mass, neck computed tomography (CT) is necessary for urgent surgical conditions such as deep neck infections. Our aim was to evaluate the diagnostic effectiveness of and proper patient selection for neck CT as a method for the initial evaluation of pediatric neck masses in the emergency department. We analyzed the medical records of 105 pediatric patients who visited the emergency department with neck mass whose initial imaging work-up was a neck CT and who visited the emergency department with a neck mass. The parameters investigated included the patient's age, sex, symptom duration, clinical impression, CT interpretation, final diagnosis, and treatment. The positive predictive value (PPV) for CT was calculated, and the parameters that correlated with an urgent surgical condition post-CT were evaluated. The median age was 6.5 years (1 month to 12 years), and the male-to-female ratio was 2:1. The most common initial impression was acute cervical lymphadenopathy. A comparison of the final diagnosis and CT scan demonstrated that the overall PPV was 96.2%. If the initial impression was a deep neck infection, a salivary gland infection, or tonsillitis, the PPV for CT was 100%. Fever (>38.0°C) and severe tenderness were significant between patients with and without urgent surgical conditions on CT. Computed tomography could be considered as the first diagnostic modality when an urgent surgical condition such as a deep neck infection is highly suspected.


Exercise for dysmenorrhoea.
Exercise has a number of health benefits and has been recommended as a treatment for primary dysmenorrhoea (period pain), but the evidence for its effectiveness on primary dysmenorrhoea is unclear. This review examined the available evidence supporting the use of exercise to treat primary dysmenorrhoea. To evaluate the effectiveness and safety of exercise for women with primary dysmenorrhoea. We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED and CINAHL (from inception to July 2019). We searched two clinical trial databases (inception to March 2019) and handsearched reference lists and previous systematic reviews. We included studies if they randomised women with moderate-to-severe primary dysmenorrhoea to receive exercise versus no treatment, attention control, non-steroidal anti-inflammatory drugs (NSAIDs) or the oral contraceptive pill. Cross-over studies and cluster-randomised trials were not eligible for inclusion. Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. We contacted study authors for missing information. We assessed the quality of the evidence using GRADE. Our primary outcomes were menstrual pain intensity and adverse events. Secondary outcomes included overall menstrual symptoms, usage of rescue analgesic medication, restriction of daily life activities, absence from work or school and quality of life. We included a total of 12 trials with 854 women in the review, with 10 trials and 754 women in the meta-analysis. Nine of the 10 studies compared exercise with no treatment, and one study compared exercise with NSAIDs. No studies compared exercise with attention control or with the oral contraceptive pill. Studies used low-intensity exercise (stretching, core strengthening or yoga) or high-intensity exercise (Zumba or aerobic training); none of the included studies used resistance training.Exercise versus no treatmentExercise may have a large effect on reducing menstrual pain intensity compared to no exercise (standard mean difference (SMD) -1.86, 95% confidence interval (CI) -2.06 to -1.66; 9 randomised controlled trials (RCTs), n = 632; I2= 91%; low-quality evidence). This SMD corresponds to a 25 mm reduction on a 100 mm visual analogue scale (VAS) and is likely to be clinically significant. We are uncertain if there is any difference in adverse event rates between exercise and no treatment.We are uncertain if exercise reduces overall menstrual symptoms (as measured by the Moos Menstrual Distress Questionnaire (MMDQ)), such as back pain or fatigue compared to no treatment (mean difference (MD) -33.16, 95% CI -40.45 to -25.87; 1 RCT, n = 120; very low-quality evidence), or improves mental quality of life (MD 4.40, 95% CI 1.59 to 7.21; 1 RCT, n = 55; very low-quality evidence) or physical quality of life (as measured by the 12-Item Short Form Health Survey (SF-12)) compared to no exercise (MD 3.40, 95% CI -1.68 to 8.48; 1 RCT, n = 55; very low-quality evidence) when compared to no treatment. No studies reported on any changes in restriction of daily life activities or on absence from work or school.Exercise versus NSAIDsWe are uncertain if exercise, when compared with mefenamic acid, reduced menstrual pain intensity (MD -7.40, 95% CI -8.36 to -6.44; 1 RCT, n = 122; very low-quality evidence), use of rescue analgesic medication (risk ratio (RR) 1.77, 95% CI 1.21 to 2.60; 1 RCT, n = 122; very low-quality evidence) or absence from work or school (RR 1.00, 95% CI 0.49 to 2.03; 1 RCT, n = 122; very low-quality evidence). None of the included studies reported on adverse events, overall menstrual symptoms, restriction of daily life activities or quality of life. The current low-quality evidence suggests that exercise, performed for about 45 to 60 minutes each time, three times per week or more, regardless of intensity, may provide a clinically significant reduction in menstrual pain intensity of around 25 mm on a 100 mm VAS. All studies used exercise regularly throughout the month, with some studies asking women not to exercise during menstruation. Given the overall health benefits of exercise, and the relatively low risk of side effects reported in the general population, women may consider using exercise, either alone or in conjunction with other modalities, such as NSAIDs, to manage menstrual pain. It is unclear if the benefits of exercise persist after regular exercise has stopped or if they are similar in women over the age of 25. Further research is required, using validated outcome measures, adequate blinding and suitable comparator groups reflecting current best practice or accounting for the extra attention given during exercise.


Risk analysis of colorectal cancer in women with endometrial carcinoma.
Endometrial carcinoma (EC) and colorectal cancer (CRC) are closely linked in a well-documented, predominantly inherited cancer syndrome known as hereditary non-polyposis colorectal cancer (HNPCC). Epidemiological studies report that women with EC have a 1.5- to 3-fold increased risk of developing CRC. However, this elevated risk could be the consequence of genetic confounding. In order to plan a proper CRC prevention program, we sought to verify and quantify this risk, first estimating it in 697 women with EC who received treatment and follow-up in one health care district between 1986 and 2000. The standardised incidence ratio (SIR), which compares observed with expected cases of CRC in the general population, was calculated. Multiple logistic regression analysis was used to estimate the odds ratio and 95% confidence interval of a dependent variable, second primary CRC, as a function of clinical and pathological features. Multiple primary tumours were observed in 6.7% of the patients, with CRC being the second most frequently occurring type of cancer. The estimated overall risk for CRC was slightly higher than that observed in the general population, but was nonetheless not statistically significant. Multivariate analysis revealed a family history of CRC to be a risk factor for developing the disease as a second primary cancer. A BMI ≤25 and the pathological spectrum of EC were clinical and pathological features associated with CRC development, but were without statistical significance. MSH2 and MLH1 mutational screening confirmed genetic involvement in most of the CRCs observed in the cohort. Overall, the data show that women with EC have a CRC risk similar to that of the general population, and should therefore be screened on the basis of risk factors for CRC.


Practices and pitfalls in immunologic methodology.
RIA is used in thousands of laboratories around the world to measure multiple classes of substances of biologic interest, both peptidal and non-peptidal in nature. It is now evident that if there is a need to measure an organic substance of biologic interest and there is no simple method to do so, some imaginative investigator will develop the appropriate RIA procedure. Although new assays are continuously being described and their usefulness documented, these reports generally do not describe how or whether the assay has been optimized for the particular antiserum. Some of the practices and problems described in this report should serve as a guide in optimizing RIA procedures.


[Variants of the stabilization process in the late stages of malignant schizophrenia].
Of 800 patients suffering from malignant schizophrenia for 20 years and longer a group of 94 patients showing signs of the process stabilization was selected. In a part of them (76 patients), residual positive disturbances (isolated, gradually subsiding hallucinatory manifestations not accompanied with any delusional interpretations) were noted. In the rest 18 patients, the clinical picture was characterized by personality changes according to the type of a monotonous activity or apathetic debility. Prolonged absence of positive disturbances and exacerbations in these patients suggests that the morbid process in them got stabilized (residual state). This type of the schizophrenia outcome is not an indispensable stage of the psychosis termination, and is observed rather infrequently-according to the author's data, in 2% of cases only.


Accurate measurement of out-of-plane particle displacement from the cross correlation of sequential digital in-line holograms.
A new method to quantify three-dimensional particle fields using digital in-line holography is presented. From sequentially recorded holograms, the maximum cross correlation of edge sharpness within local particle windows yields an accurate measurement of particle displacements. Experiments demonstrate out-of-plane displacement uncertainty of approximately 0.15 mean particle diameters, which is roughly an order-of-magnitude improvement compared with alternative methods. Application to shotgun pellets demonstrates robustness despite experimental noise.


Evaluation of a self-help intervention to promote the health and wellbeing of marginalised people including those living with leprosy in Nepal: a prospective, observational, cluster-based, cohort study with controls.
People affected by leprosy are at increased risk of ulcers from peripheral nerve damage. This in turn can lead to visible impairments, stigmatisation and economic marginalisation. Health care providers suggest that patients should be empowered to self-manage their condition to improve outcomes and reduce reliance on services. Self-care involves carrying out personal care tasks with the aim of preventing disabilities or preventing further deterioration. Self-help, on the other hand, addresses the wider psychological, social and economic implications of leprosy and incorporates, for example, skills training and microfinance schemes. The aim of this study, known as SHERPA (Self-Help Evaluation for lepRosy and other conditions in NePAl) is to evaluate a service intervention called Integrated Mobilization of People for Active Community Transformation (IMPACT) designed to encourage both self-care and self-help in marginalised people including those affected by leprosy. A mixed-method evaluation study in Province 5, Nepal comprising two parts. First, a prospective, cluster-based, non-randomised controlled study to evaluate the effectiveness of self-help groups on ulcer metrics (people affected by leprosy only) and on four generic outcome measures (all participants) - generic health status, wellbeing, social integration and household economic performance. Second, a qualitative study to examine the implementation and fidelity of the intervention. This research will provide information on the effectiveness of combined self-help and self-care groups, on quality of life, social integration and economic wellbeing for people living with leprosy, disability or who are socially and economically marginalised in low- and middle- income countries.


MnO2-Based nanosystems for cancer therapy.
Cancer is one of the most dangerous diseases worldwide, the treatment of which is still a great problem. The increasing demand of clinical biomedicine and fast development of nanotechnology have quickly promoted the generation of diverse nanosystems for various cancer therapies. As one kind of redox active transition-metal dioxide nanomaterials, manganese dioxide (MnO2) and its nanocomposites have emerged as a novel class of nanomaterials that show superior advantages and unprecedented performances in cancer therapy due to their large surface area, good absorption and degradation ability, strong fluorescence quenching ability, high oxidation and catalytic activity, etc. According to different morphologies of MnO2, MnO2 can be divided into MnO2 nanosheets, MnO2 quantum dots (QDs), MnO2 nanocrystals, MnO2 nanowires, etc. In this review, the synthesis of MnO2, especially MnO2 nanosheets, is first introduced, followed by an introduction of the classification of MnO2 nanomaterials. Then, recent cancer therapeutic applications of MnO2 and its nanocomposites are comprehensively overviewed, which are categorized into three parts: chemotherapy, phototherapy and synergistic therapy. In addition, treatment of other diseases based on MnO2 and its nanocomposites is also discussed. Finally, some crucial unresolved problems, probable challenges and future perspectives about the rational design and construction of MnO2-based nanosystems for further biomedical applications are also discussed.


Image quality in low-dose coronary computed tomography angiography with a new high-definition CT scanner.
A new generation of high definition computed tomography (HDCT) 64-slice devices complemented by a new iterative image reconstruction algorithm-adaptive statistical iterative reconstruction, offer substantially higher resolution compared to standard definition CT (SDCT) scanners. As high resolution confers higher noise we have compared image quality and radiation dose of coronary computed tomography angiography (CCTA) from HDCT versus SDCT. Consecutive patients (n = 93) underwent HDCT, and were compared to 93 patients who had previously undergone CCTA with SDCT matched for heart rate (HR), HR variability and body mass index (BMI). Tube voltage and current were adapted to the patient's BMI, using identical protocols in both groups. The image quality of all CCTA scans was evaluated by two independent readers in all coronary segments using a 4-point scale (1, excellent image quality; 2, blurring of the vessel wall; 3, image with artefacts but evaluative; 4, non-evaluative). Effective radiation dose was calculated from DLP multiplied by a conversion factor (0.014 mSv/mGy × cm). The mean image quality score from HDCT versus SDCT was comparable (2.02 ± 0.68 vs. 2.00 ± 0.76). Mean effective radiation dose did not significantly differ between HDCT (1.7 ± 0.6 mSv, range 1.0-3.7 mSv) and SDCT (1.9 ± 0.8 mSv, range 0.8-5.5 mSv; P = n.s.). HDCT scanners allow low-dose 64-slice CCTA scanning with higher resolution than SDCT but maintained image quality and equally low radiation dose. Whether this will translate into higher accuracy of HDCT for CAD detection remains to be evaluated.