The Geriatric Feelings of Burdensomeness Scale (GFBS).
The present article describes the development and psychometric evaluation of the Geriatric Feelings of Burdensomeness Scale using two samples of older adults collected through Amazon Mechanical Turk. The scale is a 25-item measure of general subjective feeling of being a burden on or problem for others. The goal of the measure is to capture a broad conceptualization of burdensomeness that is relevant to a variety of important psychological variables. Two studies are described, including item development and selection, and the examination of reliability and validity evidence in a sample of 192 older adults. The estimates of reliability (coefficient alpha and average interitem correlations) were strong. Preliminary examination of convergent validity evidence found significant moderate correlations between the Geriatric Feelings of Burdensomeness Scale and measures of conceptually related constructs (hopelessness, suicidality, perceived burdensomeness, thwarted belongingness). Small, non-significant correlations were found between three indices of religiosity, providing preliminary discriminant validity evidence. Our results provide initial psychometric support for a more general and inclusive assessment tool for measuring older adults' feelings of burdensomeness. With further research on clinical significance of feelings of burdensomeness and predictive validity, this measure may be used to identify concerns and beliefs about burdensomeness among distressed older adults.


Information Technology-Based Management of Clinically Healthy COVID-19 Patients: Lessons From a Living and Treatment Support Center Operated by Seoul National University Hospital.
South Korea took preemptive action against coronavirus disease (COVID-19) by implementing extensive testing, thorough epidemiological investigation, strict social distancing, and rapid treatment of patients according to disease severity. The Korean government entrusted large-scale hospitals with the operation of living and treatment support centers (LTSCs) for the management for clinically healthy COVID-19 patients. The aim of this paper is to introduce our experience implementing information and communications technology (ICT)-based remote patient management systems at a COVID-19 LTSC. We adopted new electronic health record templates, hospital information system (HIS) dashboards, cloud-based medical image sharing, a mobile app, and smart vital sign monitoring devices. Enhancements were made to the HIS to assist in the workflow and care of patients in the LTSC. A dashboard was created for the medical staff to view the vital signs and symptoms of all patients. Patients used a mobile app to consult with their physician or nurse, answer questionnaires, and input self-measured vital signs; the results were uploaded to the hospital information system in real time. Cloud-based image sharing enabled interoperability between medical institutions. Korea's strategy of aggressive mitigation has "flattened the curve" of the rate of infection. A multidisciplinary approach was integral to develop systems supporting patient care and management at the living and treatment support center as quickly as possible. Faced with a novel infectious disease, we describe the implementation and experience of applying an ICT-based patient management system in the LTSC affiliated with Seoul National University Hospital. ICT-based tools and applications are increasingly important in health care, and we hope that our experience will provide insight into future technology-based infectious disease responses.


Anti-inflammatory steroids without pituitary-adrenal suppression.
When two new steroids, methyl prednisolonate and methyl 20-dihydroprednisolonate, were applied locally their anti-inflammatory activities were nearly equivalent to those of the parent compound prednisolone in the cotton pellet granuloma bioassay. However, when these two derivatives were administered systemically, their anti-inflammatory activities were weaker than those of the parent compound. Furthermore, unlike the parent compound, these new anti-inflammatory steroids did not suppress pituitary-adrenal function or cause liver glycogen depletion in rats.


A Comparison of Pavlik Harness Treatment Regimens for Dislocated But Reducible (Ortolani+) Hips in Infantile Developmental Dysplasia of the Hip.
Variation exists in the Pavlik harness (PH) treatment regimen for infantile developmental dysplasia of the hip (DDH). The purpose of this study was to determine if the daily PH wear duration (23 vs. 24 h) and frequency of follow-up visits affect the clinical and radiographic outcomes of infants with dislocated but reducible (Ortolani+) hips. This study reviewed prospectively enrolled patients with DDH in a single center who presented at age <6 months with Ortolani+ hips and were treated with PH. Recommended daily PH wear duration (23 vs. 24 h) and the frequency of clinic visits in first 4 weeks after the initiation of PH treatment were analyzed. The clinical success (stable hip that did not require closed or open reduction or the use of an abduction orthosis) and radiographic success based on the acetabular index at 2-year follow-up were compared between different PH regimen groups. Sixty-two patients (74 hips, 53 females) with Ortolani+ hips had a mean age of presentation of 23±28 days (range, 4 to 128 d) and mean follow-up of 33.2±18.4 months (range, 8 to 85 mo). Overall clinical success rate of PH for Ortolani+ hips was 93% (69/74 hips) and radiographic success rate at 2 years was 84% (48/57 hips). There was no difference in clinical or radiographic success rate between the 23- and 24-hour wear groups (P>0.99, 0.73) or between hips assessed almost weekly compared with once or twice during the first 4 weeks of PH treatment (P>0.99 for both). The 23- versus 24-hour PH regimen and frequency of clinic visits in the first 4 weeks of PH treatment did not affect the clinical or radiographic success rate of Ortolani+ hips in infantile DDH. A strict weekly clinic visit and 24-hour PH regimen may not be necessary to obtain stable reduced hips in infants presenting <6 months of age with Ortolani+ hips. Level III-therapeutic.


[What do diabetic patients and what should they do to avoid errors in the course of treatment?].
To report the precautions taken by diabetic patients to avoid treatment errors and to provide advice to increase their safety. A descriptive study of patients' behaviors to minimize errors and tips by professionals to improve safety. Ninety-nine insulin-treated patients were randomly recruited from 3 primary healthcare centers and 2 hospitals. An opportunity sample of 33 doctors and nurses was also surveyed. Information of all prescriptions (p = 0.005), review of doubts before the visit (p = 0,009), and diet adherence (p = 0.02) were the only precautions reported by patients that related to a lower number of patient errors. Female patients better follow at home instructions for blood glucose monitoring (odds ratio 0.07; 95% confidence interval (CI) 0.1-0.6) and use pillboxes to avoid errors (odds ratio 0.23; 95% CI 0.1-0.6) more frequently than male patients. Male patients more commonly carry with them a card with information about allergies (odds ratio 5.03; 95% CI 1.4-17.5). Patients with a longer course of disease tend to withhold information about other treatments from their doctors (β -15.8; 95% CI -23.2-8.4). For healthcare professionals, safety may increase if patients: play a more active role in their treatment (91%), and inform their doctors about their different treatments (88%). Promotion of patient autonomy, improved communication to patients, and systematic information about the most common medication errors may contribute to patient safety.


Transgenic plants expressing the AaIT/GNA fusion protein show increased resistance and toxicity to both chewing and sucking pests.
The adoption of pest-resistant transgenic plants to reduce yield losses and decrease pesticide use has been successful. To achieve the goal of controlling both chewing and sucking pests in a given transgenic plant, we generated transgenic tobacco, Arabidopsis, and rice plants expressing the fusion protein, AaIT/GNA, in which an insecticidal scorpion venom neurotoxin (Androctonus australis toxin, AaIT) is fused to snowdrop lectin (Galanthus nivalis agglutinin, GNA). Compared with transgenic tobacco and Arabidopsis plants expressing AaIT or GNA, transgenic plants expressing AaIT/GNA exhibited increased resistance and toxicity to one chewing pest, the cotton bollworm, Helicoverpa armigera. Transgenic tobacco and rice plants expressing AaIT/GNA showed increased resistance and toxicity to two sucking pests, the whitefly, Bemisia tabaci, and the rice brown planthopper, Nilaparvata lugens, respectively. Moreover, in the field, transgenic rice plants expressing AaIT/GNA exhibited a significant improvement in grain yield when infested with N. lugens. This study shows that expressing the AaIT/GNA fusion protein in transgenic plants can be a useful approach for controlling pests, particularly sucking pests which are not susceptible to the toxin in Bt crops.


Niosomal gel of lornoxicam for topical delivery: in vitro assessment and pharmacodynamic activity.
Lornoxicam is a potent oxicam class of non steroidal anti-inflammatory agent, prescribed for mild to moderate pain and inflammation. Niosomal gel of lornoxicam was developed for topical application. Lornoxicam niosomes (Lor-Nio) were fabricated by thin film hydration technique. Bilayer composition of niosomal vesicles was optimized. Lor-Nio dispersion was characterized by DSC, XRD, and FT-IR. Morphological evaluation was performed by scanning electron microscopy (SEM). Lor-Nio dispersion was incorporated into a gel using 2% w/w Carbopol 980 NF. Rheological and texture properties of Lor-Nio gel formulation showed suitability of the gel for topical application. The developed formulation was evaluated for in vitro skin permeation and skin deposition studies, occlusivity test and skin irritation studies. Pharmacodynamic activity of the Lor-Nio gel was performed by carragenan-induced rat paw model. Optimized Lor-Nio comprised of Span 60 and cholesterol in a molar ratio of 3:1 with 30 μM dicetyl palmitate as a stabilizer. It had particle size of 1.125 ± 0.212 μm (d 90), with entrapment efficiency of 52.38 ± 2.1%. DSC, XRD, and IR studies showed inclusion of Lor into niosomal vesicles. SEM studies showed spherical closed vesicular structure with particles in nanometer range. The in vitro skin permeation studies showed significant improvement in skin permeation and skin deposition for Lor-Nio gel (31.41 ± 2.24 μg/cm(2), 30.079 ± 1.2 μg/cm(2)) over plain lornoxicam gel (7.37 ± 1.27 μg/cm(2), 6.6 ± 2.52 μg/cm(2)). The Lor-Nio gel formulation showed enhanced anti-inflammatory activity by exhibiting mean edema inhibition (87.69 ± 1.43%) which was significantly more than the plain lornoxicam gel (53.84 ± 2.21%).


Ag3SnCuP10: [Ag3Sn] tetrahedra embedded between adamantane-type [P10] cages.
Ag3SnCuP10 was synthesized from a stoichiometric mixture of copper, silver, tin, and red phosphorus, with SnI4 added as a mineralization agent. Cubic Ag3SnCuP10, space group F3m (No. 216) with lattice parameter a = 10.503(1) A and Z = 4, consisting of orientationally disordered [Ag3Sn] heteroclusters and adamantane-type [P10] cages, is one example in which structure determination was possible only by the combined use of diffraction and spectroscopic methods. An ideal 4-fold domain twin structure that results for a R3m model, featuring an ordered arrangement of the heteroclusters, cannot be differentiated from the F3m model by diffraction methods alone. After a detailed NMR spectroscopic examination using state of the art solid-state NMR techniques, we found the local environment around the [P10] cages of the F3m model to be the correct description of the Ag3SnCuP10 structure. A possible Cu/Ag or Ag/Sn disorder in the [Ag3Sn] heterocluster and within the copper substructure was excluded by Mössbauer spectroscopic investigations and NMR measurements.


Repair of ventricular septal defect in a child with severe pulmonary hypertension--response to inhaled nitric oxide.
Nitric oxide (NO), was administered successfully, to a child with severe pulmonary hypertension, following surgical repair of a large ventricular septal defect. Inhalation of NO, 20-25 parts per million (ppm) was continued for 24 h, resulting in mean pulmonary artery pressure (PAP) of 25 mmHg and permitting a reduction in both ventilatory and inotropic support. Weaning of NO was commenced. At 5 ppm, administration was discontinued. An immediate and dramatic increase in PAP occurred. A similar pattern resulted on further attempts, demonstrating the extreme sensitivity of the pulmonary vasculature to the effects of inhaled low dose NO and the selectivity of the response.


Statins' dosage in patients with renal failure and cyclosporine drug-drug interactions in transplant recipient patients.
Dyslipidemia is frequent in patients with renal failure and in transplant recipient patients. This lead to a wide use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with impaired renal function or in patients treated with cyclosporine as post-transplantation immunosuppressive therapy. As a result, it is crucial for those patients' physicians to be aware of how to handle these drugs when renal function is impaired and/or when cyclosporine is co-administered. Most statins have an extensive hepatic elimination and the renal route is usually a minor elimination pathway. However, pharmacokinetic alterations have been described for some of these drugs in patients with renal insufficiency. Cyclosporine is a widely used immunosuppresive therapy in solid organ transplant patients and drug-drug interactions are likely to occur when statins and cyclosporine are administered together. Those interactions may theoretically result in increased statins and/or cyclosporine serum levels with potential muscle and/or renal toxicity. As a result, caution is warranted if concurrent administration is performed. In this review, we synthesized the data from the literature on (1) the pharmacokinetics and dosage adjustment of atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin in patients with renal failure and (2) the potential drug-drug interactions between these drugs and cyclosporine in transplant recipient patients.


Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads.
A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation. Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction? Lead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings. There are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an "inching" evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear. This case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.


Immunization strategies against pulmonary tuberculosis: considerations of T cell geography.
Pulmonary tuberculosis (TB) remains a global health concern with an astounding 9 million new cases and 2 million deaths per year. This leading infectious cause of death remains highly prevalent with one third of the world's population latently infected with Mycobacterium tuberculosis (M.tb) despite routine vaccination against TB in endemic areas. The only approved TB vaccine is the Bacille Calmette-Guerin (BCG), which provides protection against childhood miliary tuberculosis and has been administered intradermally in humans for almost a century. While effective in preventing disseminated forms of TB, the BCG has variable efficacy in providing protection against pulmonary TB. Therefore, the BCG has been unable to control the instance of adult pulmonary TB which constitutes the global disease burden. Despite the fact that mechanisms underlying the lack of pulmonary protection provided by the BCG remain poorly understood, it remains the "Gold Standard" for vaccine-mediated protection against M.tb and will continue to be used for the foreseeable future. Therefore, continued effort has been placed on understanding the mechanisms behind the failure of BCG to provide sufficient protection against M.tb in the lung and to design new vaccines to be used in conjunction with the BCG as boost strategies to install protective immunity at the site of infection. Growing evidence supports that the route of immunization dictates the geographical location of TB-reactive T cells, and it is this distribution which predicts the protective outcome of such vaccine-elicited immunity. Such vaccines that are able to localize TB-reactive T cells to the lung and airway mucosa are thought to fill the "immunological gap" in the lung that is required for enhanced protection against M.tb infection. This chapter focuses on the critical importance of T cell geography when designing new immunization strategies against pulmonary TB.


Early growth response transcriptional regulators are dispensable for macrophage differentiation.
Early growth response (Egr) proteins comprise a family of transcriptional regulators (Egr1-4) that modulate gene expression involved in the growth and differentiation of many cell types. In particular, Egr1 is widely believed to have an essential role in regulating monocyte/macrophage differentiation. However, Egr1-deficient mice have normal numbers of functional macrophages, an observation that has led to the hypothesis that other Egr proteins may compensate for Egr1 function in vivo. We examined whether other Egr transcription factors have a functionally redundant role in monocyte/macrophage differentiation. Egr1 and Egr3 expression was found to be induced in myeloid cells when they were differentiated into macrophages by treatment with M-CSF, whereas Egr2 was minimally induced and Egr4 was not detected. In either Egr1/Egr3 or Egr1/Egr2 double homozygous mutant mice, macrophage differentiation and function remained unimpaired. Additionally, the expression of molecules that broadly inhibit Egr function failed to block commitment to the monocytic lineage or inhibit the maturation of monocyte precursors. Finally, several hemopoietic growth factors were found to induce Egr gene expression, indicating that Egr gene expression is not cell lineage specific. Taken together, these results demonstrate that Egr transcription factors are neither essential for nor specific to monocyte/macrophage differentiation.


A Novel Approach to Oropharyngeal Foreign Body Removal.
Grill wire brush bristle foreign bodies most commonly embed in the oropharynx. Often these bristles can be removed in the clinic; however, on occasion, the patient requires general anesthesia for retrieval because of the gag reflex and difficulty with access and visualization. We report here on 2 cases of patients who underwent successful transoral robotic surgical retrieval of wire bristles from the base of tongue after unsuccessful direct laryngoscopy. Otolaryngologists should be aware of the use of robotic assistance for oropharyngeal foreign body retrieval.


Educating early childhood care and education providers to improve knowledge and attitudes about reporting child maltreatment: A randomized controlled trial.
Early childhood care and education providers (CCPs) work with over 7 million young children. These children are vulnerable to physical, sexual and emotional abuse, and neglect. However, CCPs make less than 1% of all reports of suspected child abuse and neglect that are made to child protective services. CCPs are therefore an untapped resource in the public health response to child maltreatment. However, their knowledge and attitudes about duties to report child maltreatment are poorly understood. Moreover, no rigorous research has tested whether their knowledge and attitudes about reporting child maltreatment can be improved. These gaps in knowledge are important because knowledge of the duty and positive attitudes towards it produce more effective reporting, and little evidence exists about how to enhance cognitive and affective attributes. Using the CONSORT approach, we report a single-blind test-retest randomized controlled trial evaluating iLook Out for Child Abuse, a customized online educational intervention for CCPs to increase knowledge and attitudes towards the reporting duty. 762 participants were randomized with results analyzed for 741 participants (372 in the intervention group; 369 in the control). Knowledge of the reporting duty increased in the intervention group from 13.54 to 16.19 out of 21 (2.65 increase, 95% CI: (2.37, 2.93); large effect size 0.95, p < 0.001); the control group remained stable, moving from 13.54 to 13.59 (0.05 increase, 95% CI: (-0.12, 0.22); negligible effect size 0.03, p = 0.684). Attitudes were enhanced on all 13 items for the intervention group, remaining stable in the control, with significant differences between groups on all items (p < 0.05). Gains were largely sustained at four month follow-up. Findings support education for CCPs and other professions. Future research should also explore effects of education on reporting behavior. US National Institutes of Health NCT02225301.


Biovectoring of plastic by white storks from a landfill to a complex of salt ponds and marshes.
Research into plastic pollution has extensively focused on abiotic vectors, overlooking transport by animals. Opportunistic birds, such as white storks (Ciconia ciconia) often forage on landfills, where plastic abounds. We assess plastic loading by ingestion and regurgitation of landfill plastic in Cadiz Bay, a major stopover area for migratory white storks in south-west Spain. On average, we counted 599 storks per day moving between a landfill and a complex of salt ponds and marshes, where they regurgitated pellets that each contained a mean of 0.47 g of plastic debris, dominated by polyethylene. Modelling reliant on GPS tracking estimated that 99 kg and >2 million particles of plastic were biovectored into the wetland during 2022, with seasonal peaks that followed migration patterns. GPS data enabled the correction of field censuses and the identification of plastic deposition hotspots. This study highlights the important role that biovectoring plays in plastic transport into coastal wetlands.


Behavior segmentation by boys as a function of aggressiveness and prior information.
Previous research documents a hostile attribution bias by aggressive boys when considering a social situation with ambiguous cues as to the intention of the participants. The present research evaluated whether this bias extends to the manner in which boys process incoming information. Aggressiveness of boys in grades 3-6 was assessed with peer behavior nominations. In a separate session, each child viewed a videotape of 2 boys playing tag on a playground and segmented the actions using a standard behavior segmentation procedure. A critical event occurred when one of the boys fell down after being tagged, slowly got up, then resumed the game. Prior to viewing the videotape each child received one of three information conditions: benign (the boys were friends), hostile (the boys did not like one another), or neutral (no specific information about the relationship between the boys). Aggressiveness predicted change in segmentation after the critical event only in the neutral prior information condition. Thus aggressiveness, found in other research to be associated with a hostile attribution bias, also was found to be related to differences in the organization of incoming information.


Assembling the spindle midzone in the right place at the right time.
During anaphase the mitotic spindle extends dramatically, promoting the segregation of the chromosomes into the two daughter cells. The spindle midzone, assembled at the onset of anaphase, is critical for this extension. How this assembly is linked to progression through the cell cycle is not fully understood. Our data show that in budding yeast the conserved phosphatase Cdc14, activated in early anaphase, regulates the formation of the spindle midzone. Cdc14 dephosphorylates residues of a core midzone component, the conserved microtubule bundling factor Ase1, that were previously phosphorylated by the cyclin-dependent kinase complex. In addition, Cdc14 activation is also indirectly responsible for midzone localization of the separase-Slk19 complex. This dual control of midzone assembly by Cdc14 is necessary for the formation of the focused and centered spindle midzone that drives the continuous and full elongation of the anaphase spindle. The identification of Ase1 as a key Cdc14 substrate elucidates how spindle midzone assembly is coordinated with the metaphase to anaphase transition.


A Case of Cerebral Large-Vessel Vasculitis Concomitant Fahr Syndrome in Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus. We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome. The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis.


A Bystander Effect of Lung Cancer Chemotherapy on Chronic Echinococcal Disease.
Hydatid cystic disease is a parasitic infestation caused by Echinococcus granulosus and commonly manifests as hepatic and pulmonary cysts. When feasible, based on cyst size and location, surgical resection is potentially curative. Post-surgical recurrence of disease is encountered in up to 25% of patients. Secondary peritoneal contamination is a recognized complication in 5-10% of cases. Disseminated disease is usually palliated using systemic anti-parasitic agents such as benzimidazoles, albendazole and mebendazole but worsening of disease post-systemic treatment is frequent in 14-25% of patients. In this report, we share our experience of a patient with long-standing, chronic disseminated hydatidosis and subsequent diagnosis of non-small cell lung cancer who manifested evidence of reduced activity of the echinococcal disease following institution of chemotherapy for his new diagnosis of lung cancer. There was significant reduction in the serum level of anti-echinococcal antibody titers in tandem with chemotherapy administration. There was also minimal but notable decrease in the size of the cysts on serial cross-sectional imaging obtained for monitoring cancer response to chemotherapy. This intriguing observation of a possible benefit of anticancer chemotherapy against echinococcal disease in this index case may provide new insights for therapeutic exploration in disseminated echinococcal disease.


Inhibition of human neuroblastoma in SCID mice by low-dose of selective Cox-2 inhibitor nimesulide.
Neuroblastoma is the most common solid tumor of infants and carries a poor prognosis especially in advanced stages. The present recommended therapies carry a high risk of side effects that is associated with long-term morbidity. We evaluated the efficacy of a low dose of the selective cyclooxygenase-2 inhibitor Nimesulide in preventing human Neuroblastoma tumor growth in Severe Combined Immune-deficient mice. Mice containing established tumors (SH-SY5Y cells) treated with 20 mg/kg Nimesulide every 4th day beginning on day 1 of cell injections resulted in a 65% reduction of tumor growth compared to the DMSO treated control mice (P<0.05) but did not significantly reduce tumor growth when Nimesulide was started once tumors reached 1 cm. There was a reduction in the level of cyclooxygenase-2 protein and induction of effecter caspases in tumors treated with Nimesulide. However, there was no change in the levels of X-Inhibitor-of-Apoptosis-Protein, Smac/Diablo, or proteins of the PI3/Akt pathway following Nimesulide treatment. In Conclusion, low doses of Nimesulide can potentially be used as a chemopreventive agent for human Neuroblastoma.


High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.
While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes. No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children's Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones' levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004). Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features. Level III.


Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study.
Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.


Isolation of Campylobacter subsp. jejuni from Oriental and American cockroaches caught in kitchens and poultry houses in Vom, Nigeria.
A total of 690 adult cockroaches (Periplaneta americana (L.), the American cockroach, and Blatta orientalis (L.), the oriental cockroach) were captured alive within domestic kitchens and near poultry houses in Vom. Using selective media, their external surfaces and internal (gut) contents, after adequate decontamination of the external surfaces, were culturally examined for the presence of campylobacters. 4 isolates of Campylobacter subsp jejuni were made (0.5%); 3 from the gut contents and 1 from the external surface. Nocardia asteroides was isolated from the gut contents of a batch of ten cockroaches. The low isolation rate notwithstanding, our results suggest that cockroaches may be a potential vector of campylobacters from other sources to human food. The somewhat fortuitous isolation of Nocardia asteroides and its significance are discussed.


Human ankle plantar flexor muscle-tendon mechanics and energetics during maximum acceleration sprinting.
Tendon elastic strain energy is the dominant contributor to muscle-tendon work during steady-state running. Does this behaviour also occur for sprint accelerations? We used experimental data and computational modelling to quantify muscle fascicle work and tendon elastic strain energy for the human ankle plantar flexors (specifically soleus and medial gastrocnemius) for multiple foot contacts of a maximal sprint as well as for running at a steady-state speed. Positive work done by the soleus and medial gastrocnemius muscle fascicles decreased incrementally throughout the maximal sprint and both muscles performed more work for the first foot contact of the maximal sprint (FC1) compared with steady-state running at 5 m s(-1) (SS5). However, the differences in tendon strain energy for both muscles were negligible throughout the maximal sprint and when comparing FC1 to SS5. Consequently, the contribution of muscle fascicle work to stored tendon elastic strain energy was greater for FC1 compared with subsequent foot contacts of the maximal sprint and compared with SS5. We conclude that tendon elastic strain energy in the ankle plantar flexors is just as vital at the start of a maximal sprint as it is at the end, and as it is for running at a constant speed.


Permeable pavement and stormwater management systems: a review.
Uncontrolled stormwater runoff not only creates drainage problems and flash floods but also presents a considerable threat to water quality and the environment. These problems can, to a large extent, be reduced by a type of stormwater management approach employing permeable pavement systems (PPS) in urban, industrial and commercial areas, where frequent problems are caused by intense undrained stormwater. PPS could be an efficient solution for sustainable drainage systems, and control water security as well as renewable energy in certain cases. Considerable research has been conducted on the function of PPS and their improvement to ensure sustainable drainage systems and water quality. This paper presents a review of the use of permeable pavement for different purposes. The paper focuses on drainage systems and stormwater runoff quality from roads, driveways, rooftops and parking lots. PPS are very effective for stormwater management and water reuse. Moreover, geotextiles provide additional facilities to reduce the pollutants from infiltrate runoff into the ground, creating a suitable environment for the biodegradation process. Furthermore, recently, ground source heat pumps and PPS have been found to be an excellent combination for sustainable renewable energy. In addition, this study has identified several gaps in the present state of knowledge on PPS and indicates some research needs for future consideration.


Optimal Deployment of FiWi Networks Using Heuristic Method for Integration Microgrids with Smart Metering.
The unpredictable increase in electrical demand affects the quality of the energy throughout the network. A solution to the problem is the increase of distributed generation units, which burn fossil fuels. While this is an immediate solution to the problem, the ecosystem is affected by the emission of CO₂. A promising solution is the integration of Distributed Renewable Energy Sources (DRES) with the conventional electrical system, thus introducing the concept of Smart Microgrids (SMG). These SMGs require a safe, reliable and technically planned two-way communication system. This paper presents a heuristic based on planning capable of providing a bidirectional communication that is near optimal. The model follows the structure of a hybrid Fiber-Wireless (FiWi) network with the purpose of obtaining information of electrical parameters that help us to manage the use of energy by integrating conventional electrical system with SMG. The optimization model is based on clustering techniques, through the construction of balanced conglomerates. The method is used for the development of the clusters along with the Nearest-Neighbor Spanning Tree algorithm (N-NST). Additionally, the Optimal Delay Balancing (ODB) model will be used to minimize the end to end delay of each grouping. In addition, the heuristic observes real design parameters such as: capacity and coverage. Using the Dijkstra algorithm, the routes are built following the shortest path. Therefore, this paper presents a heuristic able to plan the deployment of Smart Meters (SMs) through a tree-like hierarchical topology for the integration of SMG at the lowest cost.


Percent body fat, skinfold thickness or body mass index for defining obesity or overweight, as a risk factor for asthma in schoolchildren: which one to use in epidemiological studies?
None of the epidemiological studies indicating that obesity is a risk factor for asthma in schoolchildren have used the percent body fat (PBF) to define obesity. The present study compares the definition of obesity using body mass index (BMI), PBF and the raw sum of the thickness of four skinfolds (SFT) to evaluate this condition as a risk factor for asthma. All classes of children of the target ages of 6-8 years of all schools in four municipalities of Murcia (Spain) were surveyed. Participation rate was 70.2% and the number of children included in the study was 931. Height, weight and SFT (biceps, triceps, subscapular and suprailiac) were measured according to standard procedures. Current active asthma was defined from several questions of the International Study of Asthma and Allergies in Childhood questionnaire. Obesity was defined using two standard cut-off points for BMI and PBF, and the 85th percentile for BMI, PBF and SFT. The highest quartile of each type of measurement was also compared with the lowest. A multiple logistic regression analysis was made for the various obesity definitions, adjusting for age, asthma in the mother and father and gender. The adjusted odds ratios of having asthma among obese children were different for boys and girls and varied across the different obesity definitions. For the standard cut-off points of BMI they were 1.19 [95% confidence interval (CI) 0.41-3.43] for girls and 2.00 (95% CI 0.97-4.10) for boys; however, for PBF (boys 25%, girls 30%) the corresponding figures were 1.54 (95% CI 0.63-3.73) and 1.20 (95% CI 0.66-2.21). BMI, PBF and SFT showed more consistency between each other when using the other cut-off points. BMI, PBF (except standard cut-off points) and SFT produce relatively comparable results when analysing the interaction between obesity and asthma.


Simultaneous dimerization and SU(4) symmetry breaking of 4-color fermions on the square lattice.
Using infinite projected entangled-pair states, exact diagonalization, and flavor-wave theory, we show that the SU(4) Heisenberg model undergoes a spontaneous dimerization on the square lattice, in contrast with its SU(2) and SU(3) counterparts, which develop Néel and three-sublattice stripelike long-range order. Since the ground state of a dimer is not a singlet for SU(4) but a 6-dimensional irreducible representation, this leaves the door open for further symmetry breaking. We provide evidence that, unlike in SU(4) ladders, where dimers pair up to form singlet plaquettes, here the SU(4) symmetry is additionally broken, leading to a gapless spectrum in spite of the broken translational symmetry.


Forensic determination of hair deposition time in crime scenes using electron paramagnetic resonance.
Several types of biological samples, including hair strands, are found at crime scenes. Apart from the identification of the value and the contributor of the probative evidence, it is important to prove that the time of shedding of hair belonging to a suspect or victim matches the crime window. To this end, to estimate the ex vivo aging of hair, we evaluated time-dependent changes in melanin-derived free radicals in blond, brown, and black hairs by using electron paramagnetic resonance spectroscopy (EPR). Hair strands aged under controlled conditions (humidity 40%, temperature 20-22°C, indirect light, with 12/12 hour of light/darkness cycles) showed a time-dependent decay of melanin-derived radicals. The half-life of eumelanin-derived radicals in hair under our experimental settings was estimated at 22 ± 2 days whereas that of pheomelanin was about 2 days suggesting better stabilization of unpaired electrons by eumelanin. Taken together, this study provides a reference for future forensic studies on determination of degradation of shed hair in a crime scene by following eumelanin radicals by utilizing the non-invasive, non-destructive, and highly specific EPR technique.


Finding edges in noisy scenes.
Edge detection in the presence of noise is a well-known problem. This paper examines an applications-motivated approach for solving the problem using novel techniques and presents a method developed by the authors that performs well on a large class of targets. ROC curves are used to compare this method with other well-known edge detection operators, with favorable results. A theoretical argument is presented that favors LMMSE filtering over median filtering in extremely noisy scenes. Simulated results of the research are presented.


A brief history and overview of CDC's Centers for Public Health Preparedness Cooperative Agreement Program.
The Centers for Disease Control and Prevention (CDC) funded the Centers for Public Health Preparedness (CPHP) Cooperative Agreement program from 2004 through 2010. CDC gave approximately $134 million to 27 CPHPs within accredited schools of public health to enhance the relationship between academia and state and local health agencies to strengthen public health preparedness. Over the course of the program, CPHPs provided education and training services that met public health preparedness and response needs throughout the United States. The passage of the Pandemic and All-Hazards Preparedness Act in 2006 has had broad implications for the Department of Health and Human Services' future preparedness and response activities. Guidelines were established giving accredited schools of public health eligibility to receive federal grants to carry out the continual development and delivery of core curricula and training that responds to the needs of state, local, and tribal public health authorities.


Giant cell tumors in the patellar tendon area.
Giant cell tumor of the tendon sheath is a benign tumor typically presenting as a nontender mass around the hand and wrist. Giant cell tumor of the tendon sheath in large joints is typically larger and shows higher rates of local recurrence, as well as common features with pigmented villonodular synovitis. We describe two cases of giant cell tumors in the patellar tendon area that were treated successfully with arthroscopically assisted complete excision. Orthopedic surgeons must be aware of this entity to prevent unnecessary adjuvant therapy or recurrent excision.


Potential of Minimally Invasive Tissue Sampling for Attributing Specific Causes of Childhood Deaths in South Africa: A Pilot, Epidemiological Study.
Current estimates for causes of childhood deaths are mainly premised on modeling of vital registration and limited verbal autopsy data and generally only characterize the underlying cause of death (CoD). We investigated the potential of minimally invasive tissue sampling (MITS) for ascertaining the underlying and immediate CoD in children 1 month to 14 years of age. MITS included postmortem tissue biopsies of brain, liver, and lung for histopathology examination; microbial culture of blood, cerebrospinal fluid (CSF), liver, and lung samples; and molecular microbial testing on blood, CSF, lung, and rectal swabs. Each case was individually adjudicated for underlying, antecedent, and immediate CoD by an international multidisciplinary team of medical experts and coded using the International Classification of Diseases, Tenth Revision (ICD-10). An underlying CoD was determined for 99% of 127 cases, leading causes being congenital malformations (18.9%), complications of prematurity (14.2%), human immunodeficiency virus/AIDS (12.6%), diarrheal disease (8.7%), acute respiratory infections (7.9%), injuries (7.9%), and malignancies (7.1%). The main immediate CoD was pneumonia, sepsis, and diarrhea in 33.9%, 19.7%, and 10.2% of cases, respectively. Infection-related deaths were either an underlying or immediate CoD in 78.0% of cases. Community-acquired pneumonia deaths (n = 32) were attributed to respiratory syncytial virus (21.9%), Pneumocystis jirovecii (18.8%), cytomegalovirus (15.6%), Klebsiella pneumoniae (15.6%), and Streptococcus pneumoniae (12.5%). Seventy-one percent of 24 sepsis deaths were hospital-acquired, mainly due to Acinetobacter baumannii (47.1%) and K. pneumoniae (35.3%). Sixty-two percent of cases were malnourished. MITS, coupled with antemortem clinical information, provides detailed insight into causes of childhood deaths that could be informative for prioritization of strategies aimed at reducing under-5 mortality.


Blood lipids and the incidence of atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis and the Framingham Heart Study.
Dyslipidemia is a major contributor to the development of atherosclerosis and coronary disease. Its role in the etiology of atrial fibrillation (AF) is uncertain. We studied 7142 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Framingham Heart Study who did not have prevalent AF at baseline and were not on lipid-lowering medications. Total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standard procedures. Incident AF during follow-up was identified from hospital discharge codes; review of medical charts; study electrocardiograms; and, in MESA only, Medicare claims. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of AF by clinical categories of blood lipids in each cohort. Study-specific results were meta-analyzed using inverse of variance weighting. During 9.6 years of mean follow-up, 480 AF cases were identified. In a combined analysis of multivariable-adjusted results from both cohorts, high levels of high-density lipoprotein cholesterol were associated with lower AF risk (hazard ratio 0.64, 95% CI 0.48 to 0.87 in those with levels ≥60 mg/dL versus <40 mg/dL), whereas high triglycerides were associated with higher risk of AF (hazard ratio 1.60, 95% CI 1.25 to 2.05 in those with levels ≥200 mg/dL versus <150 mg/dL). Total cholesterol and low-density lipoprotein cholesterol were not associated with the risk of AF. In these 2 community-based cohorts, high-density lipoprotein cholesterol and triglycerides but not low-density lipoprotein cholesterol or total cholesterol were associated with the risk of AF, accounting for other cardiometabolic risk factors.


Documentation of significant electron transport defects on the reducing side of photosystem II upon removal of the PsbP and PsbQ extrinsic proteins.
The Photosystem II extrinsic proteins PsbO, PsbP, and PsbQ are required for efficient oxygen-evolving activity under physiological conditions. In this study, we have used fluorescence decay kinetics to quantitatively probe Photosystem II electron transport upon depletion of these components by standard salt washing protocols. Our results indicate that in addition to the expected oxidizing-side defects, removal of PsbP and PsbQ with 2 M NaCl significantly slows the rate of electron transfer from Q(A)(-) to Q(B). Electron transfer from Q(A)(-) to Q(B) in Photosystem II reaction centers with an occupied Q(B) site was slowed by a factor of 12, while electron transport from Q(A)(-) to Q(B) in centers with an unoccupied Q(B) site was slowed by a factor of 6. Subsequent removal of the PsbO protein by treatment with 200 mM NaCl and 2.6 M urea did not induce further reducing-side alterations. Our results demonstrate that studies attributing defects observed upon PsbP and PsbQ removal solely to the oxidizing side must be viewed with caution.


Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project.
The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as "required" or "recommended" for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate "required" markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5-20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for "required" diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. "Recommended" markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as "required" for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus "recommended" panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated. © 2017 International Clinical Cytometry Society.


Macroscopic response in active nonlinear photonic crystals.
We derive macroscopic equations of motion for the slowly varying electric field amplitude in three-dimensional active nonlinear optical nanostructures. We show that the microscopic Maxwell equations and polarization dynamics can be simplified to a macroscopic one-dimensional problem in the direction of group velocity. For a three-level active material, we derive the steady-state equations for normal mode frequency, threshold pumping, nonlinear Bloch mode amplitude, and lasing in photonic crystals. Our analytical results accurately recapture the results of exact numerical methods.


Appearance of bound states in random potentials with applications to soliton theory.
We analyze the stochastic creation of a single bound state (BS) in a random potential with a compact support. We study both the Hermitian Schrödinger equation and non-Hermitian Zakharov-Shabat systems. These problems are of special interest in the inverse scattering method for Korteveg-de-Vries and the nonlinear Schrödinger equations since soliton solutions of these two equations correspond to the BSs of the two aforementioned linear eigenvalue problems. Analytical expressions for the average width of the potential required for the creation of the first BS are given in the approximation of delta-correlated Gaussian potential and additionally different scenarios of eigenvalue creation are discussed for the non-Hermitian case.


Preferred features of a fluorine-19 MRI probe for amyloid detection in the brain.
Fluorine-19 magnetic resonance imaging (19F MRI) could be a promising approach for imaging amyloid deposition in the brain. However, the required features of a 19F MRI probe for amyloid detection remain unclear. In the present study, we investigated a series of compounds as potent 19F probes that could prevent the reduction in MR signal when bound to amyloid plaques in the brain. Each compound consists of styrylbenzoxazole as a core structure linked by a different length of polyethylene glycol (PEG) chain to one of three types of fluorine-labeled group: a trifluoroethoxy group, a hexafluoroisopropoxy group, or a 3',5'-bis(trifluoromethyl)benzylamino group. Among these compounds, 6-(3',6',9',15',18',21'-heptaoxa-23',23',23'-trifluoro tricosanyloxy)-2-(4'-dimethylaminostyryl)benzoxazole [compound 3b (m = 6)], which has a trifluoroethoxy group with seven ethylene glycol groups in the PEG chain, showed significant 19F MR signals in the brains of AβPPswe/PS1dE9 double-transgenic mice, but not wild-type mice. This suggested that compound 3b (m = 6) could be a useful 19F MRI probe for amyloid detection. Furthermore, this study identified the most effective length of PEG chain between the fluorine-labeled group and the core structure to ensure a strong MR signal when the probe is bound to amyloid plaques.


On multivariate imputation and forecasting of decadal wind speed missing data.
This paper demonstrates the application of multiple imputations by chained equations and time series forecasting of wind speed data. The study was motivated by the high prevalence of missing wind speed historic data. Findings based on the fully conditional specification under multiple imputations by chained equations, provided reliable wind speed missing data imputations. Further, the forecasting model shows, the smoothing parameter, alpha (0.014) close to zero, confirming that recent past observations are more suitable for use to forecast wind speeds. The maximum decadal wind speed for Entebbe International Airport was estimated to be 17.6 metres per second at a 0.05 level of significance with a bound on the error of estimation of 10.8 metres per second. The large bound on the error of estimations confirms the dynamic tendencies of wind speed at the airport under study.


Correlation filter: an accurate approach to detect and locate low contrast character strings in complex table environment.
Correlation has been used extensively in object detection field. In this paper, two kinds of correlation filters, Minimum Average Correlation Energy (MACE) and Extended Maximum Average Correlation Height (EMACH), are applied as adaptive shift locators to detect and locate smudgy character strings in complex tabular color flight coupon images. These strings in irregular tabular coupon are computer-printed characters but of low contrast and could be shifted out of the table so that we cannot detect and locate them using traditional algorithms. In our experiment, strings are extracted in the preprocessing phase by removing background and then based on geometric information, two correlation filters are applied to locate expected fields. We compare results from two correlation filters and demonstrate that this algorithm is a high accurate approach.


[Pulmonary mucormycosis. A case of successful treatment and a review of the literature].
A patient with documented mucormycosis survived after nephrectomy, lobectomy and Amphotericin B therapy. This is only the twentieth successfully treated patient with pulmonary mucormycosis reported in the English literature. A review of the literature reveals that aggressive surgical debridement remains the sine qua non for a successful outcome. However, Amphotericin B provides a necessary adjunct to the treatment of this systemic disease.


Disease activity in ankylosing spondylitis and associations to markers of vascular pathology and traditional cardiovascular disease risk factors: a cross-sectional study.
To compare the risk of cardiovascular disease (CVD) in ankylosing spondylitis (AS) and population controls, and to examine the associations between disease activity and CVD risk. A cross-sectional study was done of patients with AS grouped according to Ankylosing Spondylitis Disease Activity Score (ASDAS) into ASDAS-high and ASDAS-low. Markers of vascular pathology, impaired endothelial function [asymmetric dimethylarginine (ADMA)], and arterial stiffness [augmentation index (AIx) and pulse wave velocity (PWV)], and traditional CVD risk factors [blood pressure, lipids, body mass index (BMI), CVD risk scores] were compared between AS and controls as well as across ASDAS-high versus ASDAS-low versus controls using ANCOVA analyses. Altogether, 151 patients with AS and 134 controls participated. Patients had elevated ADMA (µmol/l) and AIx (%) compared to controls: mean difference (95% CI): 0.05 (0.03, 0.07), p < 0.001 and 2.6 (0.8, 4.3), p = 0.01, respectively. AIx increased with higher ASDAS level, p(trend) < 0.04. There were no significant group differences of PWV. BMI was higher in ASDAS-high compared to ASDAS-low (p = 0.02). Total cholesterol was lower in AS compared to controls, and lower with higher ASDAS, p(trend) = 0.02. CVD risk scores were similar across groups except for Reynolds Risk Score, where the ASDAS-high group had a significantly higher score, compared to both ASDAS-low and controls. Elevated ADMA and AIx in AS support a higher CVD risk in AS. Elevated AIx and BMI in AS with high ASDAS indicate an association between disease activity and CVD risk. Lower total cholesterol in AS may contribute to underestimation of CVD risk.


Self-focusing and spherical aberrations in corneal tissue during photodisruption by femtosecond laser.
The use of ultrashort pulse lasers is current in refractive surgery and has recently been extended to corneal grafting (keratoplasty). When performing keratoplasty, however, permanent degradation of the optical properties of the patient's cornea compromises the penetration depth of the laser and the quality of the incisions, therefore causing unwanted secondary effects. Additionally, corneal grafting needs considerably higher penetration depths than refractive surgery. Little data are available about the interaction processes of the femtosecond pulses in the volume of pathological corneas-i.e., in the presence of spherical aberrations and optical scattering. We investigate the influence of the focusing numerical aperture on the laser-tissue interaction. We point out that at low numerical apertures (NAs), tissue damage is produced below and above the focal region. We attribute this phenomenon to nonlinear self-focusing effects. On the other hand, at high NAs, spherical aberrations become significant when focusing at high depths for posterior surgeries, which also limit the cutting efficiency. As high NAs are advisable for reducing unwanted nonlinear effects and ensure accurate cutting, particular attention should be paid to aberration management when developing clinical femtosecond lasers.


Combined cyclectomy-trabeculectomy procedure for refractory glaucoma.
A new surgical technique for cases of refractory glaucoma is described. The technique has been performed on 42 severely glaucomatous eyes. The technique consists of a partial excision of the ciliary body combined with a trabeculectomy to maintain an effective filtration by several passages. All excised material was verified as ciliary body by an ophthalmic pathologist. The follow-up period was 2 to 5 years. Intraocular pressure decreased after the operation and remained less than 20 mm Hg in 39 eyes. The visual acuity increased in 8 of 42 eyes and remained the same in 32 eyes. Complications were similar to those seen after trabeculectomy. This method is efficient for severely glaucomatous eyes that are difficult to manage with trabeculectomy alone.


Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.
The Belgrade (b) rat has an autosomal recessively inherited, microcytic, hypochromic anemia associated with abnormal reticulocyte iron uptake and gastrointestinal iron absorption. The b reticulocyte defect appears to be failure of iron transport out of endosomes within the transferrin cycle. Aspects of this phenotype are similar to those reported for the microcytic anemia (mk) mutation in the mouse. Recently, mk has been attributed to a missense mutation in the gene encoding the putative iron transporter protein Nramp2. To investigate the possibility that Nramp2 was also mutated in the b rat, we established linkage of the phenotype to the centromeric portion of rat chromosome 7. This region exhibits synteny to the chromosomal location of Nramp2 in the mouse. A polymorphism within the rat Nramp2 gene cosegregated with the b phenotype. A glycine-to-arginine missense mutation (G185R) was present in the b Nramp2 gene, but not in the normal allele. Strikingly, this amino acid alteration is the same as that seen in the mk mouse. Functional studies of the protein encoded by the b allele of rat Nramp2 demonstrated that the mutation disrupted iron transport. These results confirm the hypothesis that Nramp2 is the protein defective in the Belgrade rat and raise the possibility that the phenotype shared by mk and b animals is unique to the G185R mutation. Furthermore, the phenotypic characteristics of these animals indicate that Nramp2 is essential both for normal intestinal iron absorption and for transport of iron out of the transferrin cycle endosome.


Optomechanical spectroscopy with broadband interferometric and quantum cascade laser sources.
The spectral tunability of semiconductor-metal multilayer structures can provide a channel for the conversion of light into useful mechanical actuation. Responses of suspended silicon, silicon nitride, chromium, gold, and aluminum microstructures are shown to be utilized as a detector for visible and IR spectroscopy. Both dispersive and interferometric approaches are investigated to delineate the potential use of the structures in spatially resolved spectroscopy and spectrally resolved microscopy. The thermoplasmonic, spectral absorption, interference effects, and the associated energy deposition that contributes to the mechanical response are discussed to describe the potential of optomechanical detection in future integrated spectrometers.


Transient receptor potential melastatin 2 is involved in trinitrobenzene sulfonic acid-induced acute and chronic colitis-associated fibrosis progression in mice.
Crohn's disease, a chronic and recurrent gastrointestinal disease, frequently causes intestinal fibrosis. Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is activated by reactive oxygen species. This study investigated the role of TRPM2 in acute colitis and chronic colitis-associated fibrosis progression. Acute colitis and chronic colitis-associated fibrosis were induced in TRPM2-deficient (TRPM2KO) and wild-type (WT) mice through single and repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Bone marrow-derived macrophages (BMDMs) from WT and TRPM2KO mice were stimulated using H2O2. In WT mice, a single TNBS injection induced acute colitis with upregulated inflammatory cytokines/chemokines and Th1/Th17-related cytokines, while repeated TNBS injections induced chronic colitis-associated fibrosis with upregulation of fibrogenic factors and Th2-related cytokines. Acute colitis and chronic colitis-associated fibrosis with cytokines/chemokine upregulation and fibrogenic factors were considerably suppressed in TRPM2KO mice. Treating BMDMs with H2O2 increased cytokine/chemokine expression and JNK, ERK, and p38 phosphorylation; however, these responses were significantly less in TRPM2KO than in WT mice. These findings suggest that TRPM2 contributes to acute colitis progression via Th1/Th17-mediated immune responses. Furthermore, TRPM2 may be directly involved in colitis-associated fibrosis induction, likely due to the regulation of Th2/TGF-β1-mediated fibrogenesis in addition to a consequence of acute colitis progression.


[Decreased synthetic activity as a possible cause of the death of Escherichia coli bacteria during amino acid starvation].
The work is concerned with studying the breakdown of proteins and RNA when a polyauxotrophic Escherichia coli strain is incubated in a salt solution without amino acids, phosphorus, nitrogen and glucose at 43 degrees C as well as the ability of starving bacterial cells to recommence protein and RNA synthesis (also in the course of phage T4 infection) and to reproduce bacteriophages T4, lambda and MS2. Within the first two hours of the incubation, 12% of proteins and 40% of RNA break down to acid-soluble fragments. Then protein degradation stops while RNA decomposition goes on, but at a lower rate. Within 4-6 h of starvation, the rate of protein and RNA synthesis drops down 4-5 times and the survival rate equals 40-60% when the cells are transferred onto a complete medium. The quantitative characteristics of phages T4, lambda and MS2 reproduction fall down in prestarved cells. The authors speculate that E. coli cells die off in the course of starvation not because some unique structure is destroyed, but owing to the fact that the activity of enzymes and ribosomes gradually declines. As a result, the synthetic activity of the cell drops down abruptly and irreversibly because the enzymes are inactivated and RNA breaks down, which eventually causes cell death.


Proteolytic inactivation of an extracellular (1-->3)-beta-glucanase from the fungus Acremonium persicinum is associated with growth at neutral or alkaline medium pH.
The filamentous fungus Acremonium persicinum released high levels of proteolytic enzyme activity into the culture fluid during growth at pH 7 or above. Almost total inhibition of this crude activity by phenylmethylsulfonyl fluoride suggested that it was mainly due to the presence of a serine protease. This protease inactivated one of three extracellular (1-->3)-beta-glucanases produced by this fungus, although the activities of the remaining two (1-->3)-beta-glucanases did not appear to be affected. Growth of A. persicinum in acidic conditions resulted in the presence of much lower extracellular proteolytic activity and no apparent (1-->3)-beta-glucanase inactivation.


Brachytherapy for patients with uveal melanoma: historical perspectives and future treatment directions.
Surgical management with enucleation was the primary treatment for uveal melanoma (UM) for over 100 years. The Collaborative Ocular Melanoma Study confirmed in 2001 that globe-preserving episcleral brachytherapy for UM was safe and effective, demonstrating no survival difference with enucleation. Today, brachytherapy is the most common form of radiotherapy for UM. We review the history of brachytherapy in the treatment of UM and the evolution of the procedure to incorporate fine-needle-aspiration biopsy techniques with DNA-and RNA-based genetic prognostic testing.


Early and dynamic expression of cSfrp1 during chick embryo development.
Secreted frizzled related proteins (SFRPs) are a new class of signalling molecules that appear to antagonise the activity of the Wnt proteins. Here we report the dynamic expression pattern of cSfrp1, a new member of this family, at early stages of chick embryo development. cSfrp1 transcripts are first detected at pre-streak stages throughout the chick blastula but, during early primitive streak formation, expression is restricted to the anterior primitive streak and later to the blastoderm anterior to the Hensen' s node. This pattern of expression overlaps with that of Otx2 and is complementary to that of cWnt8c. During neural plate formation cSfrp1 mRNAs are abundantly localized only to the anterior domain of the embryo but, as neural tube closes, the expression extends caudally. Later, the main sites of expression in the neural tissue are the telencephalic vesicles, the epiphysis, the developing eyes and the ventral hindbrain and neural tube. Additionally, cSfrp1 transcripts were found in the axial and lateral mesoderm, the otic placode, the trigeminal ganglia, the mesoderm of the branchial arches, the developing limb buds, as well as in the mesodermal component of the developing kidney.


Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington's disease.
Supplementing brain cholesterol is emerging as a potential treatment for Huntington's disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the blood-brain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses. Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction. In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.


A ménage à trois: the eye, the hand and on-line processing.
This review summarizes research conducted in our laboratories over the past 5 years aimed at determining the temporal and spatial relationships between eye and hand movements and the amount of central processing that must occur before performing a manual aiming movement, relative to the amount of processing that is done online. All of our research to date points to a two-component model of speed-accuracy control in manual aiming. Several studies have shown that eye and hand movements in manual aiming are inextricably linked both temporally and spatially. Typically, the eye arrives in the vicinity of the target first; this coincides with peak acceleration of the finger during the initial impulse phase of a movement. There is also significant temporal and spatial coupling of the finger, elbow and shoulder in aiming, and movements appear to evolve in a proximal-to-distal fashion. Movements are endpoint driven and variability is reduced with distal approximation to the target. This movement control strategy means that visual information is not only available for use in modifying responses, but there is sufficient time available for its use. In sequential complex aiming movements, the use of visual feedback and on-line processing become even more important. Practice does not diminish the need for on-line processing; rather, its use appears to ensure greater movement efficiency.


Does Sound Influence Perceived Duration of Visual Motion?
Multimodal perception is a key factor in obtaining a rich and meaningful representation of the world. However, how each stimulus combines to determine the overall percept remains a matter of research. The present work investigates the effect of sound on the bimodal perception of motion. A visual moving target was presented to the participants, associated with a concurrent sound, in a time reproduction task. Particular attention was paid to the structure of both the auditory and the visual stimuli. Four different laws of motion were tested for the visual motion, one of which is biological. Nine different sound profiles were tested, from an easier constant sound to more variable and complex pitch profiles, always presented synchronously with motion. Participants' responses show that constant sounds produce the worst duration estimation performance, even worse than the silent condition; more complex sounds, instead, guarantee significantly better performance. The structure of the visual stimulus and that of the auditory stimulus appear to condition the performance independently. Biological motion provides the best performance, while the motion featured by a constant-velocity profile provides the worst performance. Results clearly show that a concurrent sound influences the unified perception of motion; the type and magnitude of the bias depends on the structure of the sound stimulus. Contrary to expectations, the best performance is not generated by the simplest stimuli, but rather by more complex stimuli that are richer in information.


Development of an efficient technique for gene deletion and allelic exchange in Geobacillus spp.
Geobacillus thermoglucosidasius is a thermophilic, natural ethanol producer and a potential candidate for commercial bioethanol production. Previously, G. thermoglucosidasius has been genetically modified to create an industrially-relevant ethanol production strain. However, creating chromosomal integrations and deletions in Geobacillus spp. is laborious. Here we describe a new technique to create marker-less mutations in Geobacillus utilising a novel homologous recombination process. Our technique incorporates counter-selection using β-glucosidase and the synthetic substrate X-Glu, in combination with a two-step homologous recombination process where the first step is a selectable double-crossover event that deletes the target gene. We demonstrate how we have utilised this technique to delete two components of the proteinaceous shell of the Geobacillus propanediol-utilization microcompartment, and simultaneously introduce an oxygen-sensitive promoter in front of the remaining shell-component genes and confirm its functional incorporation. The selectable deletion of the target gene in the first step of our process prevents re-creation of wild-type which can occur in most homologous recombination techniques, circumventing the need for PCR screening to identify mutants. Our new technique therefore offers a faster, more efficient method of creating mutants in Geobacillus.


National Trends in the Surgical Management of Urinary Incontinence among Insured Women, 2004 to 2013: The Urologic Diseases in America Project.
The objective of this study was to examine national trends in the surgical management of urinary incontinence in women in the United States from 2004 to 2013. We analyzed the CDM (Optum® de-identified Clinformatics® Data Mart) for women 18 to 64 years old and the CMS (Centers for Medicare and Medicaid Services) Medicare 5% Sample for women 65 years old or older. We created annual cross-sectional cohorts and assessed trends in the annual prevalence of urinary incontinence related surgical procedures overall and by age, race/ethnicity and geographic region. We observed a decline in the percent of women with urinary incontinence who underwent surgical treatment according to the CMS (from 4.7% in 2004 to 2.7% in 2013) and the CDM (from 12.5% in 2004 to 9.1% in 2013). This trend persisted independently of age, race/ethnicity and geographic region. Slings were the most common procedure but started to decline in 2011, ultimately decreasing by about 50% during the study period. Compared to other groups the prevalence of urinary incontinence related surgical procedures, including slings, was highest among women 35 to 54 years old and White women, and lowest among women residing in the Northeast. These sociodemographic patterns persisted with time. During the study period injection procedures remained stable, sacral neuromodulation increased slightly but remained uncommon and suspension decreased to nearly 0% of all anti-incontinence procedures. Surgical management of female urinary incontinence experienced several shifts from 2004 to 2013, including a decline in sling procedures. Age, racial/ethnic and regional differences in treatment persisted with time. Improved understanding of the drivers of these trends may help direct future development of treatments of pelvic floor disorders.


Zinc Complexes Derived from 5-Bromo-2-(((2-isopropylamino)ethyl)imino)methyl)phenol: Microwave-Assisted Synthesis, Characterization, Crystal Structures and Antibacterial Activities.
Three new zinc complexes [Zn3L2(μ2-η1:η1-CH3COO)2(μ2-η2:η0-CH3COO)2] (1), [ZnCl2(HL)] (2) and [ZnBr2(HL)] (3), where L = 5-bromo-2-(((2-isopropylamino)ethyl)imino)methyl)phenolate, HL = 5-bromo-2-(((2-isopropylammonio)ethyl)imino)methyl)phenolate, have been synthesized under microwave irradiation. The complexes were characterized by elemental analyses, IR, UV-Vis spectra, molar conductivity, and single crystal X-ray diffraction. X-ray analysis revealed that the Zn atoms in complex 1 are in square pyramidal and octahedral coordination, and those in complexes 2 and 3 are in tetrahedral coordination. The molecules of the complexes are linked through hydrogen bonds and π···π interactions. In order to evaluate the biological activity of the complexes, in vitro antibacterial against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa was assayed.


Phosphoproteomics of the Arabidopsis plasma membrane and a new phosphorylation site database.
Functional genomic technologies are generating vast amounts of data describing the presence of transcripts or proteins in plant cells. Together with classical genetics, these approaches broaden our understanding of the gene products required for specific responses. Looking to the future, the focus of research must shift to the dynamic aspects of biology: molecular mechanisms of function and regulation. Phosphorylation is a key regulatory factor in all aspects of plant biology; but it is difficult, if not impossible, for most researchers to identify in vivo phosphorylation sites within their proteins of interest. We have developed a large-scale strategy for the isolation of phosphopeptides and identification by mass spectrometry (Nühse et al., 2003b). Here, we describe the identification of more than 300 phosphorylation sites from Arabidopsis thaliana plasma membrane proteins. These data will be a valuable resource for many fields of plant biology and overcome a major impediment to the elucidation of signal transduction pathways. We present an analysis of the characteristics of phosphorylation sites, their conservation among orthologs and paralogs, and the existence of putative motifs surrounding the sites. These analyses yield general principles for predicting other phosphorylation sites in plants and provide indications of specificity determinants for responsible kinases. In addition, more than 50 sites were mapped on receptor-like kinases and revealed an unexpected complexity of regulation. Finally, the data also provide empirical evidence on the topology of transmembrane proteins. This information indicates that prediction programs incorrectly identified the cytosolic portion of the protein in 25% of the transmembrane proteins found in this study. All data are deposited in a new searchable database for plant phosphorylation sites maintained by PlantsP (http://plantsp.sdsc.edu) that will be updated as the project expands to encompass additional tissues and organelles.


Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy.
To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy (PMRT). Locoregional control, disease-free survival, overall survival and treatment-related toxicities. This guideline is based on a review of all meta-analyses, consensus statements and other guidelines published between 1966 and November 2002. Searches of MEDLINE and CANCERLIT for English-language randomized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously reviewed by the American Society of Clinical Oncology (ASCO) Health Services Research Committee panel in its published guideline. A nonsystematic review of the literature was continued through June 2003. Locoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall). Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes. The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. These women should be offered the opportunity to participate in clinical trials of PMRT. Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes. Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear. PMRT should encompass the chest wall and the supraclavicular, infraclavicular and axillary apical lymph node areas. To reduce the risk of lymphedema, radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes. A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT cannot be made because of limited and inconsistent data. The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure, particularly to the cardiac and pulmonary structures. Common short-term side effects of PMRT, including fatigue and skin erythema, are generally tolerable and not dose-limiting. Severe long-term side effects, including lymphedema, cardiac and pulmonary toxicities, brachial plexopathy, rib fractures and secondary neoplasms, are relatively rare. The optimal sequencing of PMRT and systemic therapy is currently unclear. Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity. The authors' original text was submitted for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 11 oncologists from across Canada. The final document was approved by the steering committee. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. COMPLETION DATE: November 2003.


The cost-effectiveness of harm reduction.
HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term.


Urine phthalate determinations as an index of occupational exposure to phthalic anhydride and di(2-ethylhexyl)phthalate.
Although it has been estimated that over 600 000 workers in the United States are exposed to di(2-ethylhexyl)phthalate (DEHP), an animal carcinogen, and that over 100 000 are exposed to phthalic anhydride (PA), few data are available on levels of phthalates in biological fluids of these workers. For a determination of occupational exposure to PA and DEHP at a plant manufacturing DEHP from PA and 2-ethylhexanol, air samples were taken for PA and DEHP, and pre- and postshift urine samples were collected for the determination of total phthalates. Urine samples were obtained from 48 workers in jobs with high exposure to phthalates and from 47 workers in jobs with low exposure. The airborne concentrations of DEHP ranged from 20 to 4 110 micrograms/m3, and the concentrations of PA ranged from 4 to 203 micrograms/m3. The most heavily exposed workers had the highest mean postshift urine phthalate concentration (geometric mean 7.6 nmol/ml) (p = 0.015), and also the greatest mean increase (4.4 nmol/ml) in preshift to postshift urine phthalate levels. Twofold increases over the shift in urine phthalate concentration and postshift phthalate levels of greater than 10 nmol/ml were observed in 8 (25%) of 32 chemical operators, but in none of 52 other workers. These data suggest that measurement of urine phthalate levels may have utility for monitoring the exposure of workers manufacturing or using PA.


Waveform estimation techniques for event-related bioelectric signals: a study of performance.
Many bioelectric signals result from the electrical response of a physiological system to an impulse that can be internal (ECG signals) or external (evoked potentials). A comparative study of performance of seven waveform estimation techniques used for event-related signals that are time-locked to a stimulus is presented in this paper. Computer generate 1 signals and noise for several signal-to-noise ratios (SNRs) are used to make ensembles of simulated noisy waveforms. The performance of each technique is numerically investigated using the root-mean-squared error and two well known SNR estimators. The results show that an adaptive impulse correlated filter performs the best. It is capable of estimating the deterministic component of the signal and removes the noise uncorrelated with stimulus even if this noise is colored and without the need for prealignment.


Does fetal screening affect women's worries about the health of their baby? A randomized controlled trial of ultrasound screening for Down's syndrome versus routine ultrasound screening.
Screening for fetal abnormality may increase women's anxiety as attention is directed at the possibility of something being wrong with the baby. The aim of this study was to evaluate the effect of ultrasound screening for Down's syndrome on women's anxiety in mid-pregnancy and 2 months after delivery. Two thousand and twenty-six women were randomly allocated to an ultrasound examination at 12-14 gestational weeks (gws) including risk assessment for Down's syndrome or to a routine scan at 15-20 gws. Questionnaires including the State-Trait Anxiety Inventory (STAI), the Cambridge Worry Scale (CWS), and the Edinburgh Postnatal Depression Scale (EPDS) were filled in at baseline in early pregnancy, at 24 gws and 2 months after delivery. No statistically significant differences were found between the trial groups regarding women's worries about the health of the baby, general anxiety and depressive symptoms during pregnancy or 2 months after delivery. Women's worries about something being wrong with the baby in the early ultrasound group and routine group, respectively, decreased from baseline (39.1% versus 36.0%) to mid-pregnancy (29.2% versus 27.8%), and finally to 2 months after delivery (5.2% versus 6.6%). Fetal screening for Down's syndrome by an early ultrasound scan did not cause more anxiety or concerns about the health of the baby in mid-pregnancy or 2 months after birth than in women who had a routine scan.


Laser-driven ramp-compression experiments on the national ignition facility.
This report details the analyses and related uncertainties in measuring longitudinal-stress-density paths in indirect laser-driven ramp equation-of-state (EOS) experiments [Smith et al., Nat. Astron. 2(6), 452-458 (2018); Smith et al., Nature 511(7509), 330-333 (2014); Fratanduono et al., Science 372(6546), 1063-1068 (2021); and Fratanduono et al., Phys. Rev. Lett. 124(1), 015701 (2020)]. Experiments were conducted at the National Ignition Facility (NIF) located at the Lawrence Livermore National Laboratory. The NIF can deliver up to 2 MJ of laser energy over 30 ns and provide the necessary laser power and control to ramp compress materials to TPa pressures (1 TPa = 10 × 106 atmospheres). These data provide low-temperature solid-state EOS data relevant to the extreme conditions found in the deep interiors of giant planets. In these experiments, multi-stepped samples with thicknesses in the range of 40-120 µm experience an initial shock compression followed by a time-dependent ramp compression to peak pressure. Interface velocity measurements from each thickness combine to place a constraint on the Lagrangian sound speed as a function of particle velocity, which in turn allows for the determination of a continuous stress-density path to high levels of compressibility. In this report, we present a detailed description of the experimental techniques and measurement uncertainties and describe how these uncertainties combine to place a final uncertainty in both stress and density. We address the effects of time-dependent deformation and the sensitivity of ramp EOS techniques to the onset of phase transformations.


Synthesis of Hydride-Doped Perovskite Stannate with Visible Light Absorption Capability.
Narrow-gap semiconductors with visible light absorption capability have attracted attention as photofunctional materials. H--doped BaSn0.7Y0.3O3-δ containing Sn(II) species was recently reported to absorb visible light up to 600 nm, which represents the first demonstration of oxyhydride-based visible-light-absorbers. In the present study, a more detailed investigation was made to obtain information on the synthesis and properties of H--doped perovskite-type stannate with respect to the A-site cation of the material and the preparation conditions. H--doped ASn0.7Y0.3O3-δ (A = Ba, Ba0.5Sr0.5, and Sr) obtained by the reaction of ASn0.7Y0.3O3-δ precursors with CaH2 at 773 K under vacuum conditions was shown to have almost the same bandgap (ca. 2.1 eV), regardless of the A-site cation. Physicochemical measurements and theoretical calculations revealed that the identical bandgaps of H--doped ASn0.7Y0.3O3-δ are due to the simultaneous shift of the midgap states composed of Sn2+ with the conduction band minimum. Experimental results also indicated that the appropriate preparation conditions with respect to Y3+-substitution and the temperature for the synthesis of the ASn0.7Y0.3O3-δ precursors were essential to obtain H--doped products that have a low density of defects.


Cancer stem cell-immune cell crosstalk in breast tumor microenvironment: a determinant of therapeutic facet.
Breast cancer (BC) is globally one of the leading killers among women. Within a breast tumor, a minor population of transformed cells accountable for drug resistance, survival, and metastasis is known as breast cancer stem cells (BCSCs). Several experimental lines of evidence have indicated that BCSCs influence the functionality of immune cells. They evade immune surveillance by altering the characteristics of immune cells and modulate the tumor landscape to an immune-suppressive type. They are proficient in switching from a quiescent phase (slowly cycling) to an actively proliferating phenotype with a high degree of plasticity. This review confers the relevance and impact of crosstalk between immune cells and BCSCs as a fate determinant for BC prognosis. It also focuses on current strategies for targeting these aberrant BCSCs that could open avenues for the treatment of breast carcinoma.


Bacterial community in the biofilm of granular activated carbon (GAC) PreBiofilter in bench-scale pilot plants for surface water pretreatment.
Biofilters of granular activated carbon (GAC) are responsible for the removal of organic matters in drinking water treatments. PreBiofilters, which operate as the first unit in a surface water treatment train, are a cost-effective pretreatment for conventional surface water treatment and provide more consistent downstream water quality. This study investigated bacterial communities from the samples of raw surface water, biofilm on the PreBiofilter, and filtrates for surface water pretreatment. A bench-scale pilot plant of PreBiofilter was constructed to pretreat surface water from the Canoochee River, GA, USA. PreBiofilter exhibited a significant reduction of total organic carbon and dissolved organic carbon. The evenness and Shannon diversity of bacterial operational taxonomic units (OTUs) were significantly higher on the biofilm of PreBiofilter than in raw water and filtrates. Similar bacteria communities were observed in the raw water and filtrates using relative abundance of bacterial OTUs. However, the bacterial communities in the filtrates became relatively similar to those in the biofilm using presence/absence of bacterial OTUs. GAC biofilm or raw water and filtrates greatly contributed to the abundance of bacteria; whereas, bacteria sheared from colonized biofilm and entered filtrates. Evenly distributed, diverse and unique bacteria in the biofilm played an important role to remove organic matters from surface water for conventional surface water pretreatment.


Identification of three additional femAB-like open reading frames in Staphylococcus aureus.
Three new proteins, FmhA, FmhB and FmhC, with significant identities to FemA and FemB were identified in the Staphylococcus aureus (ATCC 55748) genome database. They were mapped to the SmaI-C, SmaI-H and SmaI-A fragments of the S. aureus 8325 chromosome, respectively. Whereas insertional inactivation of fmhA and fmhC had no effects on growth, antibiotic susceptibility, lysostaphin resistance, or peptidoglycan composition of the strains, fmhB could not be inactivated, strongly suggesting that fmhB may be an essential gene. As deduced from the functions of FemA and FemB which are involved in the synthesis of the peptidoglycan pentaglycine interpeptide, FmhB may be a candidate for the postulated FemX thought to add the first glycine to the nascent interpeptide.


Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland.
Novel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost-benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.