A Systematic Review of Cochlear Implantation in Temporal Bone Fractures and the Significance of Otic Capsule Involvement.
Head trauma can cause deafness in cases with and without a skull base fracture. Anatomic disruption can occur with skull base fractures, but inner ear structures can also be damaged by the concussive forces of the trauma even without fracture. It is thought that negative prognostic indicators for successful cochlear implantation (CI) for hearing rehabilitation include fractures involving the otic capsule or ossification of the cochlea. This review evaluates success of CI in posttrauma patients. PubMed/MEDLINE, Cochrane, and Embase. Search terms used were "cochlear implant" AND ("trauma" OR "fracture"). Studies including preoperative computed tomography or magnetic resonance imaging and patient-level outcome data were included. Study design, perioperative and postoperative outcomes, and complications were reported. Success rates of CI were compared using χ analysis. Twenty-three studies encompassing 88 patients who experienced posttraumatic deafness and received subsequent CI were included. CI was reported as successful for 28 of 34 patients (82%) with otic capsule-involving fracture, as compared with 17 of 22 (77%) in those who had an otic capsule-sparing temporal bone fracture, and 15 of 17 (88%) of patients without evidence of fracture (i.e., concussive inner ear injury). In patients with posttraumatic hearing loss, success rates do not significantly differ between cases that do or do not involve fractures of the otic capsule. CI for posttraumatic hearing loss is generally successful.


SPIDR: a highly multiplexed method for mapping RNA-protein interactions uncovers a potential mechanism for selective translational suppression upon cellular stress.
RNA binding proteins (RBPs) play crucial roles in regulating every stage of the mRNA life cycle and mediating non-coding RNA functions. Despite their importance, the specific roles of most RBPs remain unexplored because we do not know what specific RNAs most RBPs bind. Current methods, such as crosslinking and immunoprecipitation followed by sequencing (CLIP-seq), have expanded our knowledge of RBP-RNA interactions but are generally limited by their ability to map only one RBP at a time. To address this limitation, we developed SPIDR (Split and Pool Identification of RBP targets), a massively multiplexed method to simultaneously profile global RNA binding sites of dozens to hundreds of RBPs in a single experiment. SPIDR employs split-pool barcoding coupled with antibody-bead barcoding to increase the throughput of current CLIP methods by two orders of magnitude. SPIDR reliably identifies precise, single-nucleotide RNA binding sites for diverse classes of RBPs simultaneously. Using SPIDR, we explored changes in RBP binding upon mTOR inhibition and identified that 4EBP1 acts as a dynamic RBP that selectively binds to 5'-untranslated regions of specific translationally repressed mRNAs only upon mTOR inhibition. This observation provides a potential mechanism to explain the specificity of translational regulation controlled by mTOR signaling. SPIDR has the potential to revolutionize our understanding of RNA biology and both transcriptional and post-transcriptional gene regulation by enabling rapid, de novo discovery of RNA-protein interactions at an unprecedented scale.


Thermophilic anaerobic digestion of source-sorted organic fraction of household municipal solid waste: start-up procedure for continuously stirred tank reactor.
Two feeding strategies for start-up of continuously stirred tank reactors (CSTR) treating source-sorted organic fraction of household municipal solid waste (SS-OFMSW) at 55 degrees C were evaluated. Two reactors were started up separately with a limited amount of initial inoculum (i.e. 10% of the final volume of 3.5l) and operated in a fed batch mode until the reactors were filled (30 days). A reference reactor was filled up with 3.5l of inoculum and fed at a constant rate (11.4 g volatile solids (VS)/d). Loading at progressively increasing rate (from 1.7 to 15 gVS/d), as calculated based on an activated biomass concept, showed superior process performance compared to a fixed feed rate (5.7 gVS/d). Methane yield of 0.32 m(3)/kg VS was produced during the start-up in reactor filled at progressively increasing rate and was comparable to the reference reactor. On the contrary, significant inhibition due to volatile fatty acid (VFA) build-up, mainly due to butyrate, was noticed in the reactor filled at constant rate. Thus, low initial and progressive increasing inoculum loading rate could be used as a strategy for a successful start-up of CSTR treating SS-OFMSW as it allowed a gradual acclimation of the biomass. Lab-scale results were further reaffirmed from the start-up of a full-scale plant (7000 m(3) total capacity) which was supplied with inoculum corresponding to approx. 16% of final volume and operated in a fed batch mode until the reactors were filled (58 days). Stable biogas production with low VFA (<3 g/L; based on titration method) were noticed during the start-up period when fed at progressively increasing rate. Thus, a controlled and reliable start-up procedure was found essential, which could allow rapid process stabilization and time to focus on other technical aspects of plant operation. In addition, the influence of substrate to inoculum amount (1.5-30% TS) and temperature (5-65 degrees C) on anaerobic degradation and methane production of SS-OFMSW was investigated in batch assays as a protocol for start-up procedure.


Crystal structure of squid rhodopsin.
Invertebrate phototransduction uses an inositol-1,4,5-trisphosphate signalling cascade in which photoactivated rhodopsin stimulates a G(q)-type G protein, that is, a class of G protein that stimulates membrane-bound phospholipase Cbeta. The same cascade is used by many G-protein-coupled receptors, indicating that invertebrate rhodopsin is a prototypical member. Here we report the crystal structure of squid (Todarodes pacificus) rhodopsin at 2.5 A resolution. Among seven transmembrane alpha-helices, helices V and VI extend into the cytoplasmic medium and, together with two cytoplasmic helices, they form a rigid protrusion from the membrane surface. This peculiar structure, which is not seen in bovine rhodopsin, seems to be crucial for the recognition of G(q)-type G proteins. The retinal Schiff base forms a hydrogen bond to Asn 87 or Tyr 111; it is far from the putative counterion Glu 180. In the crystal, a tight association is formed between the amino-terminal polypeptides of neighbouring monomers; this intermembrane dimerization may be responsible for the organization of hexagonally packed microvillar membranes in the photoreceptor rhabdom.


A new species of the genus Thiodia Hbner, [1825] (Lepidoptera: Tortricidae) from South Kazakhstan.
Thiodia leucocitron sp. nov. is described from South Kazakhstan. Male and female genitalia of the species and habitus of imago are illustrated. The new species is well distinguished from the congeners by genitalia of both sexes. The description is based on material collected by the author in Karatau Mts. in 2019.


Frameworks for Evaluating Medicines in Children.
To summarise contemporary approaches to evaluating medicines in children, emphasizing topics that are often misunderstood by one or more stakeholder groups. A narrative review that integrates the literature with experience in multiple settings. Children and young people need specific approaches to research about drugs because of growth and development. Specific approaches include practicalities such as the volume, frequency and technique of blood samples, and recruitment, including consent by proxy decision-makers and assent by children/young people. The design of drug development programmes includes working with children/young people from an early stage and minimising the burden of research through careful design while optimizing the contribution of extant, high quality information (including extrapolation).Regulators, academics, the pharmaceutical industry and other communities are well-placed to support pediatric drug development. Regulatory challenges include legislation that drives the extension to children of medicines used in adults (rather than a focus on the needs of children) and diversity between jurisdictions. Academics can improve the impact of their work by ensuring that data can be used in drug development programmes after they have answered a well-defined study question. Pharmaceutical companies, and public research funders can promote good return on the investment made in research (including the investment made by children/young people) by supporting data management to allow data reuse. a greater understanding of pediatric issues is relevant to diverse research communities that work to advance pharmacotherapy.


Determination of a new angiotensin converting enzyme inhibitor and its active metabolite in plasma and urine by gas chromatography-mass spectrometry.
A specific and sensitive gas chromatographic-mass spectrometric method for the simultaneous quantification of unchanged 3-[( 1-ethoxycarbonyl-3-phenyl-(1S)-propyl]amino)-2,3,4,5-tetrahydro-2-oxo-1- 1-(3S)-benzazepine-1-acetic acid (I) and its active metabolite, the dicarboxylic acid (II), in plasma and urine has been developed and validated. 2H5-labelled analogues of I and II were used as internal standards. The compounds were isolated from plasma and urine under acidic conditions using XAD-2 resin or Extrelut 1 columns. Following derivatization with diazomethane, the samples were analysed by packed-column gas chromatography-electron-impact mass spectrometry with selected-ion monitoring. The analysis of spiked plasma and urine samples demonstrated the good accuracy and precision of the method, which is suitable for use in pharmacokinetic and bioavailability studies with the new angiotensin converting enzyme inhibitor prodrug I.HCl in humans.


Measuring exposure to S. japonicum in China. II. Activity diaries, pathways to infection and immunological correlates.
In this study we examine the pathways to schistosomiasis exposure and infection among residents residing on two islands (large, Qingshan; small, Niangashan) in the Dongting Lake region (Hunan province) of China. An exposure model, based on activity diaries, was used to quantify an individual's square-metre-minute (sq.m.min) daily water contact. Subjects living on the small island had a significantly higher (P=0.0002) degree of exposure (mean+/-S.D., 13.2+/-11.0 sq.m.min) than individuals dwelling on the large island (mean+/-S.D., 5.5+/-7.1 sq.m.min). Participants identified as stool egg positive (mean+/-S.D., 8.3+/-10.4 sq.m.min) had higher exposures than for those never treated (mean+/-S.D., 2.2+/-3.4 sq.m.min) for schistosomiasis, and these high exposures rose steadily to peak at 35-49 years of age and decline after age 50. This exposure pattern differs markedly from those reported for African or South American schistosomiasis. The majority of human water contact occurs on the lake. Egg-positive subjects reported significantly higher (P < 0.05) episodes of water contact on the lake versus their egg-negative counterparts, who reported significantly higher (P < 0.01) exposure at the aquaculture ponds. The results of path analysis revealed that sex, age, island of residence and whether a fisherman or not were the most highly significant independent predictors of lake exposure. This accounted for approximately 40% (R2=0.39) of the total lake exposure. Exposure to lake water was a strong predictor (P=0.0006) of past infection and a modest predictor (P=0.05) of current infection.


Genetic diversity and antimicrobial activity of lactic acid bacteria in the preparation of traditional fermented potato product 'tunta'.
Fermentation microorganisms, lactic acid bacteria (LAB) and yeast from 12 samples of tunta production chain were quantified, from the native potatoes used by the process fermentation of potatoes in the river up to the final product. During fermentation, the LAB population steadily increased from 3 to 4 to 8 log CFU/g during the first 8 days in the river and the yeast population increased from 2 to 3 to 3-4 log CFU/g. Overall, 115 LAB strains were isolated using a culture-dependent method. Molecular techniques and 16S rRNA gene sequencing enabled the identification of native species. In LAB isolates, members of the Lactobacillaceae (64%), Leuconostocaceae (9%) and Enterococcaceae (2%) families were identified. The most prevalent LAB species in the tunta production chain was Lactobacillus curvatus, followed by Leuconostoc mesenteroides and Lactobacillus sakei, Lactobacillus brevis and Enterococcus mundtii were also present. Only 13 LAB strains showed anti-listerial activity, and one of them, identified as En. mundtii DSM 4838T [MG031213], produced antimicrobial compounds that were determined to be proteins after treatment with proteolytic enzymes. Based on these results, we suggest that traditional fermented product-derived LAB strains from specific environments could be selected and used for technological application to control pathogenic bacteria and naturally protect food from post-harvest deleterious microbiota.


Photosynthesis and transpiration ofPinus radiata D. Don under natural conditions in a forest stand.
Gas-exchange ofPinus radiata foliage was measured with climatised cuvettes under natural light in the sun-crown of 8 m tall trees in a forest stand. Measurement began during a period of drought (ψWS -8.2 bar, ψWe -10.5 bar) and continued after elimination of soil moisture-deficit by watering (ψWS -0.5 bar, ψWe -5.5 bar). Soil and air moisture-deficits severely restricted gas-exchange. Watering resulted in an immediate decline in stomatal resistance (r s ) and an increase in net photosynthesis (P N ) of 13%. A slower progressive gas-exchange recovery occurred additionally during the 10 days after watering leading to a further decline inr s to 3 s cm-1 and an ultimate increase inP N of 38% when measured under comparable conditions at 8 mb v.p.d. Radiata pine had a high photosynthetic capacity with a measured maximumP N of 10.2 mg CO2 dm-2 h-1 total needle surface (11.4 mg CO2 g-1 DM h-1).Optimum temperature forP N in March (late summer) occurred at ca. 18°C. Rate ofP N was 95% saturated at irradiance of 900 μE m-2 s-1 and 50% saturated at only 270 μE m-2 s-1. Radiata pine needles responded directly to changes in atmospheric humidity by adjusting their stomatal diffusive resistance. As a result, between 8 and 18 mb v.p.d.P N declined by 2.3% mb-1 increase.


Shotgun proteomics datasets acquired on Gammarus pulex animals sampled from the wild.
This data article associated with the manuscript "Comparative proteomics in the wild: accounting for intrapopulation variability improves describing proteome response in a Gammarus pulex field population exposed to cadmium" refers to the shotgun proteomics analysis performed on 40 Gammarus pulex animals sampled from the wild. Proteins were extracted, digested with trypsin, and the resulting peptides were identified by tandem mass spectrometry. Here, we present the list of proteins from males and the list of proteins from females that are differentially detected between the Brameloup and the Pollon populations. Data are available via ProteomeXchange with identifiers PXD013656 and PXD013712, respectively.


Noncardiac findings on dual-isotope myocardial perfusion SPECT.
This study examined the frequency of reporting noncardiac findings (NCFs), such as malignancies from inspection of raw projection images with dual-isotope single photon emission computed tomography (SPECT) perfusion imaging, which could potentially be of greater clinical importance than myocardial perfusion imaging alone. Dual-isotope (ie, rest thallium 201 and stress technetium 99m sestamibi [MIBI] or Tc-99m tetrofosmin [TET]) SPECT myocardial perfusion imaging combines multipotential tracers for noncardiac purposes (Tl-201 for renal or splenic imaging, inflammation, or lymphoma and MIBI or TET for hepatobiliary imaging and detecting increased mitochondrial number or activity in neoplastic processes). These images are optimally interpreted with cinematic inspection of the raw projection data, but this may not be practiced uniformly in every laboratory. We reviewed 12,526 computer-generated text reports of dual-isotope perfusion SPECT studies from a 6-year period for NCFs. NCFs were categorized by organ and by probability of malignancy: high (eg, focal breast or lung uptake of MIBI or TET), intermediate (eg, lymph node uptake or thyroid abnormalities), or low (eg, filling defects in liver, kidney, spleen, or gall bladder; ascites; or pleural effusions). Confirmatory imaging studies or clinical confirmation for each NCF was sought. There were a total of 207 NCFs identified in 180 reports (1.7% of reports, ranging from 0% to 2.8% of reports of individual interpreters). Of these, 107 NCFs were unsuspected before SPECT; 24% were considered at high probability for malignancy, and 24% were considered intermediate in likelihood of malignancy. Follow-up data were available for 178 NCFs, confirming 88% of these findings, including 82% of breast foci, 62% of lung foci, 86% of hepatobiliary/spleen abnormalities, and 94% of renal abnormalities. The probability of malignancy was highest (82%) in breast or lung foci in which uptake of both Tl-201 and the Tc-99m-labeled agent was present. In patients referred for evaluation of myocardial perfusion, NCFs are unusual and require systematic and careful inspection of projection images for their detection. With Tl-201, TET, MIBI, or dual-isotope imaging, detecting and reporting NCFs may occasionally result in life-saving early cancer identification.


Predictive value of hormone determinations in the first half of pregnancy.
In a prospective randomized study serial hormone determinations (beta-hCG, HPL, P, 17-OHP, E2 and E3) were performed with 1125 pregnant women from the detection of pregnancy until delivery (n = 994) or abortion (n = 131). In 605 women carrying to term blood sampling started before the 16th wk of gestation, while 389 patients were admitted to hospital between the 16th and 20th wk of gestation. The first value of most of the hormone determinations at the time of diagnosis of pregnancy before the 16th wk was normal in more than 90% (beta-hCG 95%, P 94%, E3 94%, E2 92%, HPL 64%). In the case of women with abortion the first hormone determination was low in more than 50% (beta-hCG 51%, P 56%, E3 54%, E2 62%, HPL 62%). The predictive value was highest for beta-hCG (75%) and E2 (70%) and lowest for HPL (18%). In 249 women with threatened abortion blood samples were obtained at the first days of bleeding. At this time the highest sensitivity in detecting early abortions (before the 16th wk of pregnancy) was 82% for E2, followed by beta-hCG 74%, E3 65%, P 63%, 17-OHP 52% and HPL 34% (n = 112). In late abortion (after the 16th wk of pregnancy, n = 19) the sensitivity of all methods tested was below 40%. In the case of women with bleeding and continuation of pregnancy (n = 118) normal values were found in 95% by P, 94% by beta-hCG, 93% by HPL and E3, and 83% by 17-OHP respectively. Serial determinations in women with abortion revealed that in a normal population trophoblastic disorders with reduced beta-hCG concentrations were most common. Of the remaining patients with normal beta-hCG concentrations every third woman had low P or E2 values. The combined determination of all hormones allowed conclusions to be drawn on the cause of pregnancy failure. It could be established that prior to the 6th wk of pregnancy the determination of beta-hCG was most valuable. From the 7th wk onwards the measurement of E2 or E3 showed the highest sensitivity. Between the 11th and 14th wk of pregnancy the discriminating potency of all methods tested was equally high. After the 14th wk of pregnancy hormone determinations were of little diagnostic value.


Erratum: Overweight and obesity among children and adolescents in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.
[This corrects the article DOI: 10.17886/RKI-GBE-2018-022.].


Characterization of in vivo effects of dilithium carbamyl phosphate on dog hemoglobin structure and function.
The effect of oral administration of dilithium carbamyl phosphate on adult beagle dogs is dose related. The levels of carbamylation as mol valine hydantoin/mol hemoglobin tetramer reaches a plateau of 0.3-0.38 with daily doses of 100 mg/kg body weight. Related changes in oxygen binding by whole blood and hemoglobin amount to a 5-15% left shift in oxygen isotherms. After discontinuing the administration of carbamyl phosphate, the disappearance of modified hemoglobin with a return to normal oxygen binding values follows the gradual replacement of old cells by new cells in the circulation. When the level of in vivo carbamylation in dog blood is greater than 0.16, it is similar to the levels of in vitro carbamylation of hemoglobin SS which result in the interference with sickling of erythrocytes at low levelsof oxygen.


The interplay of age stratification and HPV testing on the predictive value of ASC-US cytology. Results from the ATHENA HPV study.
We have previously shown that human papillomavirus (HPV) genotyping, using the cobas HPV Test (Roche Molecular Systems, Pleasanton, CA), can be used to identify women with atypical squamous cells of undetermined significance (ASC-US) at the highest risk for cervical intraepithelial neoplasia (CIN) grade 2 or worse. We investigated the impact of age stratification on the risk of CIN 2 or worse in women with ASC-US and the performance of HPV genotyping in different age strata. The sensitivity of the cobas HPV Test was 93.3% in the 21- to 29-year-old age group and 67.7% in the 40 years or older group, most likely owing to pathologic misclassification of CIN 2 or worse in older women. The prevalence of CIN 2 or worse in younger women was nearly 4-fold that detected in older women and was predominantly HPV-16-related. Age-specific evaluation of ASC-US cytology in conjunction with HPV genotype status enables more effective risk assessment and could be used in clinical management.


Results of long-term follow-up of patients with superficial bladder carcinoma treated with intravesically applied bacillus Calmette-Guerin vaccine according to the schedule of 6 weekly + 6 monthly instillations.
The efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in the prevention of local recurrence and disease progression in patients with superficial bladder cancer is very well documented. This study reports the effect of BCG on disease-specific and overall survival. In this retrospective trial, we have analyzed 170 patients with stage Ta and T1 superficial bladder cancer. Patients in the control group (87 patients) we followed-up only (median follow-up of 119 months) and treated surgically or with other oncologic modalities when progression of disease was diagnosed. The BCG group consisted of 83 patients treated with 6 weekly followed by 6 monthly instillations, and they have been followed-up of median 124 months. Patients receiving BCG had statistically significant better 10-year disease specific survival (83% vs. 69%, P = 0.03). At the same time point, the local recurrence rate was 48 % and the progression rate 19% for patients treated with BCG, while 77% (P < 0.001) and 38% (P = 0.007) were results in control group. Despite numerically better in the BCG group, overall survival is not significantly different in the 2 groups (P = 0.14). BCG immunotherapy significantly increases the disease-specific survival in patients with superficial bladder carcinoma.


DNA of noninfectious and infectious integrated spleen necrosis virus (SNV) is colinear with unintegrated SNV DNA and not grossly abnormal.
The cleavage sites of eight restriction endonucleases in linear spleen necrosis virus (SNV) DNA were mapped, and the map was oriented with respect to viral RNA. With the aid of this map, several structural features of the viral DNA were elucidated: unintegrated linear SNV DNA is terminally redundant; the majority of SNV DNA molecules integrated in chicken DNA, which were previously shown to be present in many sites in cellular DNA, are colinear with unintegrated viral DNA; no tandem integration of proviral molecules is detectable; and the majority of integrated SNV DNA molecules, including integrated SNV DNA molecules previously shown to be noninfectious, do not have an altered restriction enzyme digestion pattern.


Pattern of p63 expression in squamous cell carcinoma of the oral cavity.
P63 is a recently discovered gene harbouring different isoforms by alternate splicing. The two main isoforms, TAp63 and Delta Np63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation, respectively. In addition, new isoforms have been described with the same sequence as TAp63 and Delta Np63, but lacking exon 4 (Delta 4Tap63 and Delta Np73L). P63 as detected using immunohistochemistry is present in squamous cell carcinomas. To better define the role of p63 in squamous cell carcinomas of the oral cavity (OSCC), 39 patients were investigated using immunohistochemical analysis with a monoclonal antibody recognising all p63 isoforms and an anti-Ki67 antibody. Reverse-transcription polymerase chain reaction (PCR) and nested PCR were also performed using isoform-specific primers to evaluate the p63 mRNA expression pattern. Using immunohistochemistry, p63 was always present in OSCC, and its distribution was similar to that of Ki67. The percentage of positive cells increased from normal to neoplastic mucosa, but there was no relationship between the number of p63 positive cells and prognosis. P63 mRNA was found in all patients. The truncated isoforms Delta 4TAp63 and Delta Np73L were more frequently expressed in patients presenting with metastases. Delta Np73L was found in 66.6% of tumours with lymph-node metastases, but in only 33.3% of those devoid of lymph-node metastases at presentation. An impaired expression of the p63 isoforms might favour cell proliferation and indirectly enhance the metastasising capacity of OSCC.


Erratum to radical antegrade modular pancreatosplenectomy versus standard distal pancreatosplenectomy for pancreatic cancer, a dual-institutional analysis.
This corrects the article DOI: 10.21037/cco-20-6.


Comparison of predictive performance for toxicity by accumulative dose of DVH parameter addition and DIR addition for cervical cancer patients.
We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. ${D}_{2{cm}^3}$, ${D}_{1{cm}^3}$ and ${D}_{0.1{cm}^3}$ (minimum doses to the most exposed 2 cm3, 1cm3 and 0.1 cm3 of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in ${D}_{2{cm}^3}$ were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of ${D}_{2{cm}^3}$ were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of ${D}_{2{cm}^3}$ of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.


The telephone interview is an effective method of data collection in clinical nursing research: a discussion paper.
There are varying points of view regarding the advisability and utility of using the telephone to conduct research interviews. When undertaking the Women's Recovery from Sternotomy Study, we found the telephone was an effective mechanism for data collection. Our aim is to identify the advantages and challenges of using the telephone as a mechanism for data collection in clinical nursing research. The potential benefits associated with using telephone interviews as a mechanism of data collection include (a) using economic and human resources efficiently, (b) minimizing disadvantages associated with in-person interviewing, (c) developing positive relationships between researchers and participants, and (d) improving quality of data collection. The potential challenges to telephone interviewing include (a) maintaining participant involvement, (b) maintaining clear communication, (c) communicating with participants who offer extraneous information, (d) encountering participants with health concerns, and (e) communicating with a third party. Telephone interviewing can be an effective method of data collection when interviewers understand the potential benefits as well as challenges. We offer solutions to the identified challenges and make pragmatic recommendations to enhance researcher success based on the current literature and our research practice. Supportive training for interviewers, effective communication between interviewers and with research participants, and standardized telephone follow-up procedures are needed to ensure successful telephone data collection. We have found our 'Manual of Operations' to be an effective tool that assists research assistants to meet the requirements for successful telephone interviewing.


Cross-cultural adaptation and validation of the Moral Distress Scale-Revised for nurses.
Cross-culturally adapt and validate the Moral Distress Scale-Revised for nurses. Quantitative, analytical cross-sectional study conducted with 157 nurses of two hospital institutions of Southern Brazil, one public and one philanthropic. Procedures conducted: cultural adaptation of the instrument according to international recommendations; validation for the Brazilian context. Face and content validation was considered satisfactory as assessed by a specialist committee and a pretest. The instrument demonstrated satisfactory internal consistency through frequency and intensity analysis per question in the 157 items and per subgroups of the various hospital units. Cronbach's alpha was 0.88 for the instrument and between 0.76 and 0.94 for hospital units. Pearson's correlation found a moderate association for moral distress among nurses. The Moral Distress Scale-Revised - Brazilian version is a valid instrument for the assessment of moral distress in nurses. Adaptar culturalmente e validar a Moral Distress Scale Revised para enfermeiros. Estudo quantitativo, transversal analítico, realizado com 157 enfermeiros de duas instituições hospitalares do Sul do Brasil, uma pública e uma filantrópica. Realizou-se: a adaptação cultural do instrumento segundo recomendações internacionais; e a sua validação para o contexto brasileiro. A validade de face e conteúdo foi considerada satisfatória mediante avaliação de comitê de especialistas e realização de pré-teste. Mediante análise de frequência e intensidade por questão nos 157 questionários e por subconjuntos das diferentes unidades hospitalares, o instrumento demonstrou consistência interna satisfatória, com alfa de Cronbach 0,88 para o instrumento e entre 0,76 e 0,94 para as unidades hospitalares. A correlação de Pearson identificou moderada associação de sofrimento moral nos enfermeiros. o Moral Distress Scale Revised - versão brasileira é um instrumento válido para ser utilizado na avaliação de sofrimento moral de enfermeiros.


Group vs. couple treatment of sexual dysfunctions.
Results of a study comparing the effectiveness of two formats for treating men with premature ejaculation and their female partners with orgasmic dysfunctions are described. In one treatment format, a couple was treated by a male and female cotherapy team once a week for 12 sessions. In the second treatment format, which also consisted of 12 weekly sessions, three or four couples were treated simultaneously in a group led by a cotherapy team. The five couples treated alone and the ten couples treated in the group format all received a standardized therapy program consisting of sex education, attitude restructuring, and specific suggestions for acquiring ejaculatory control for the men and an increased range of orgasmic response for the females. The results showed significant improvement for couples in both treatment formats. The group format initially showed a slight tendency toward more rapid progress than did the couple format, but by the 2-month follow-up there were no significant differences. The study demonstrates that couple group treatment is a cost-effective means for treating common male and female sexual problems.


A computer-aided diagnosis system for brain magnetic resonance imaging images using a novel differential feature neural network.
To improve the performance of brain tumor diagnosis, numerous automatic brain tumor diagnosis systems that use machine learning technologies have been proposed. However, most current systems ignore the structural symmetry of brain magnetic resonance imaging (MRI) images and regard brain tumor diagnosis as a simple pattern recognition task. As a result, the performance of the current systems is not ideal. To improve the performance of the brain tumor screening process, an innovative differential feature map (DFM) block is proposed to magnify tumor regions, and DFM blocks are further combined with squeeze-and-excitation (SE) blocks to form a differential feature neural network (DFNN). First, an automatic image rectification method is applied so that the symmetry axes of brain MRI images are approximately parallel to the perpendicular axis. Moreover, a DFNN is constructed to classify the brain MRI images into two categories: "abnormal" and "normal". The experimental results show that the average accuracy of the proposed system on two databases can reach 99.2% and 98%, and the introduction of the proposed DFM block can improve the average accuracy on these two databases by 1.8% and 1.3%, respectively, which indicates that the proposed DFM block can improve the performance of the brain tumor screening process.


Association of Injury Rates Among Players in the National Football League With Playoff Qualification, Travel Distance, Game Timing, and the Addition of Another Game: Data From the 2017 to 2022 Seasons.
Injury incidence is higher in the National Football League (NFL) than in other collision sports. Although previous research has identified that scheduling variations, including overseas games and bye week timing, does not affect concussion risk, data are currently lacking regarding the effects of scheduling variation on season-long musculoskeletal injury incidence. To determine whether higher cumulative travel distance, overseas play, an early season bye week, and an expansion of the regular season is associated with higher injury rates in the NFL. Descriptive epidemiology study. All 1275 injuries across 5 NFL seasons from 2017 to 2018 through 2021 to 2022 were reviewed retrospectively. Injury data and travel distances were extracted from publicly available sources, which were cross-referenced for validation. Injury rates were calculated per 1000 athletic-exposures (AEs). Cumulative team travel distances were compared statistically using a linear regression. Single factor analysis of variance was used to compare categorical variables. Travel distance did not significantly predict injury rates (P = .47), and there was no difference in injury rates between teams that played a game overseas versus teams that did not (19.3 injuries per 1000 AEs for both; P = .96). In addition, no difference was found in injury rates (F[109,2100[ = 0.704; P = .73) or players placed on the injured reserve list (F[99,778] = 1.70; P = .077) between various bye weeks (P = .73). Injury rates did not differ between the new 17-game regular season (18.4 per 1000 AEs) versus the previous four 16-game regular seasons (19.7 per 1000 AEs; P = .12). However, teams that did not qualify for the playoffs had a significantly higher injury rate (19.9 per 1000 AEs) as well as players on injured reserve (8.0 per 1000 AEs) than playoff-qualifying teams (18.4 and 6.8 per 1000 AEs, respectively; P < .05 for both). Over 5 NFL seasons, cumulative travel distance, overseas play, bye week timing, and adding 1 regular season game were not associated with increased injury rates in NFL players. However, a lack of regular season success was associated with higher injury rates and more players on injured reserve.


Long-term results of conservative repair of rheumatic aortic valve insufficiency.
From July 1974 to January 1986, 50 patients underwent conservative repair for rheumatic aortic valvular disease at our institution. Eleven were male and 39 female, with an average age of 39.5 years (range 17-57). The aortic lesion was associated in all cases with a predominant mitral lesion. Twenty-five also had tricuspid disease which was surgically treated in 17. Twenty-six had aortic regurgitation and 24, a mixed lesion. The surgical techniques used were: (1) commissurotomy, (2) annuloplasty, (3) cusp free edge unfolding and (4) supra-aortic crest enhancement. Two patients had one cusp extended with pericardium. There were 3 hospital deaths (6%). Six patients were lost to follow-up at different periods. Maximum follow-up was 12.58 years with a mean of 7.78 years per patient. Twelve required reoperation with 3 deaths. Three reoperations were due to failure of the mitral bioprosthesis without reoperation on the aortic valve. Of the remaining 9 patients who had aortic and mitral dysfunction, 4 had severe aortic insufficiency. The actuarial freedom from reoperation at 13 years was 75% and the overall actuarial survival was 86%. It is concluded that these surgical techniques can be applied successfully in moderate rheumatic aortic valve disease accompanying a predominant mitral lesion. This is particularly relevant when a mitral reconstruction has been performed.


Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes.
To investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach. In an open-label, parallel-group trial (NCT02877355), subjects aged 18-80 years with type 2 diabetes with mild-to-moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration-time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC0-24h,day10 ) and the maximum semaglutide plasma concentration (Cmax,day10 ), respectively. Semaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ratios (subjects with/without upper GI disease) were 1.18 (95% confidence interval [CI], 0.80, 1.75) for AUC0-24h,day10 and 1.16 (95% CI, 0.77, 1.76) for Cmax . Time to Cmax and semaglutide half-life were similar in subjects with and without upper GI disease. Oral semaglutide was well tolerated; all adverse events were mild-to-moderate, with no withdrawals because of adverse events. There was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required.


Second-trimester sonographic diagnosis of diastrophic dysplasia: report of 2 index cases.
To describe the sonographic features of diastrophic dysplasia in 2 second-trimester index offspring. Real-time sonography was performed on 2 second-trimester fetuses with no risk factors for skeletal dysplasia. Each fetus had severe bilateral upper and lower extremity long bone shortening, hitchhiker thumbs and great toes, and clubbed feet, indicating a diagnosis of diastrophic dysplasia. Index cases of diastrophic dysplasia may be correctly diagnosed on the basis of second-trimester sonography.


Involvement of protein kinase C beta1-serotonin transporter system dysfunction in emotional behaviors in stressed mice.
Selective serotonin reuptake inhibitors are the first-line antidepressants for treating major depressive and post-traumatic stress disorders. These inhibitors directly bind to the serotonin transporter (SERT). Protein kinase C (PKC) is a key regulator of SERT functions as it can attenuate SERT activity through phosphorylation and its subsequent internalization. However, whether PKC-regulated SERT functions are involved in emotional impairment in a mouse model of stress remains unclear. Using a mouse model of swim-induced stress, we investigated whether the PKC-SERT system is involved in emotional impairment and tried to identify the PKC isoforms involved in this mechanism. Mice exposed to swim stress showed enhanced immobility and decreased social interaction times compared to those in swim stress-naive mice. Moreover, significant decreases in phosphorylated PKCβI and SERT levels were observed in the prefrontal cortex of stressed mice compared to those of swim stress-naive mice. No changes in levels of other phosphorylated PKC isoforms were observed between the two groups. Phorbol 12-myristate 13-acetate (a PKC activator) administration significantly attenuated enhanced immobility and decreased social interaction time in stressed mice and increased the serotonin turnover. Further, the PKC activator increased levels of phosphorylated PKCβI or SERT and decreased cell surface localization of SERT in stressed mice. Contrary to this, chelerythrine (a PKC inhibitor) administration exacerbated the immobility and sociality of mice exposed to mild stress. Our results suggest that PKCβI activation attenuates emotional impairment by suppressing SERT function in stressed mice. Thus, PKCβI may be a key target for the development of new treatment strategies for emotional impairment in stress-related disorders.


Dataset knowledge, attitude, and trust of Indonesian selected public group toward agribiotechnology application.
The focus of this research is to present an analysis of the knowledge, attitude, and trust of selected Indonesian public groups regarding the application of Agribiotechnology. This study employs a descriptive research design. The data consists of 266 respondents in two different localities in east Java, Indonesia: Jember and Bondowoso. Eight different categories of respondents were defined: students, scientists, non-government organizations, media, policymakers, consumers, producers and religious scholars. Participants responded to items assessing their knowledge, attitudes and trust toward the use of agribiotechnology, specifically in food production and how their cultural ethics, norms, or religious beliefs influence their engagement with the technology. The findings highlighted varying perspectives on the knowledge, attitude, and trust among the eight groups towards agribiotechnology application concerning responses that emphasized several content areas such as the genetic modification of crops and plants and implications of the technology on the daily lives of the Indonesian.


Prognostic impact of discrepant Ki67 and mitotic index on hormone receptor-positive, HER2-negative breast carcinoma.
Inconsistencies between mitotic index (MI) and Ki67 measures have been identified in many breast tumour samples. The aim of this study was to describe the prognosis of hormone receptor-positive (HR+) HER2- tumours having discrepant MI and Ki67. We included a cohort of breast cancer patients initially treated by surgery between 2001 and 2005 in the Institut Curie. Breast cancer-specific survival (BCSS) and disease-free survival (DFS) were analysed according to three proliferation groups: high MI/high Ki67 (MI=3, Ki67>20%), low MI/low Ki67 (MI<3, Ki67⩽20%) and discrepant (high MI/low Ki67 or low MI/high Ki67). Among the 1430 patients, 19.6% had discrepant Ki67 and MI, 11.6% had high markers and 68.8% had low markers. The 5-year BCSS was 95.8%, 95% CI (0.93-0.98) in the discrepant group, 99.3%, 95% CI (0.993-0.999) in the low-proliferation group and 91.8%, 95% CI (0.88-0.96) in the high-proliferation group. In multivariate analysis, the survival of the discrepant group was lower than that of the low-proliferation group: BCSS hazard ratio (HR)=3.01 (1.32-6.84; P=0.008) and DFS HR=2.07, 95% CI (1.31-3.26; P=0.002). Among grade 2 tumours in multivariate analysis, DFS of the discrepant group was lower than that of the low MI/low Ki67 group: HR=1.98, 95% CI (1.14-3.46), P=0.02. Regarding BCSS, the obtained results were similar. The prognosis of patients with discrepant MI and Ki67 appears intermediate between that of low MI/low Ki67 and high MI/high Ki67 groups. These markers should be jointly analysed to clarify prognosis.


Psychological and socioeconomic status, complications and quality of life in people with spinal cord injuries after discharge from hospital in Bangladesh: a cohort study.
Mixed retrospective-prospective cohort study. To determine psychological and socioeconomic status, complications and quality of life in people with spinal cord injuries (SCI) after discharge from a hospital in Bangladesh. Bangladesh. All patients admitted in 2011 with a recent SCI to a hospital in Bangladesh were identified. Patients were interviewed by telephone in 2014 using translated versions of the SF12, the SCI Secondary Conditions Scale, the Centre for Epidemiologic Studies Depression Scale (CESDS) and the Participation Component of the WHODAS. Questions were also asked about employment, living and financial situation, and opportunities to get out of bed and out of the house. Data were stratified by ability to walk on discharge. A total of 350 people were discharged with a recent SCI in 2011. By 2014, 55 had died. Of those still living, 283 were interviewed (96% follow-up rate). At the time of interview, 47% of participants were employed. One-quarter (26%) of those who were wheelchair-dependent had a pressure ulcer. The mean (s.d.) scores for the Mental and Physical Component of the SF12 were 32.0 points (5.5) and 35.8 points (3.9), respectively. The median (interquartile range) scores for the SCI Secondary Conditions Scale, CESDS and WHODAS for those who were wheelchair-dependent were 15% (10 to 19), 11 points (9 to 18) and 26 points (23 to 26), respectively. Many people with SCI in Bangladesh are house-bound, unemployed, living in poverty and have pressure ulcers. They experience moderate rates of depression and report limited quality of life.


Characterization and localization of the Mr = 43,000 proteins associated with acetylcholine receptor-rich membranes.
A protein of Mr = 43,000 (43K protein) is a major component of highly purified postsynaptic membranes isolated from Torpedo electric organ. It can be removed from these membranes by alkaline treatment or with 10 mM lithium diiodosalicylate, conditions which extract peripheral membrane proteins without solubilizing the acetylcholine receptor. Two-dimensional polyacrylamide gel electrophoresis of the lithium diiodosalicylate extract shows it to contain several major Mr = 43,000 components of isoelectric points between 7.0 and 8.0 and a minor component of approximately pI 5.6. The pI 5.6 polypeptide co-migrates with skeletal muscle actin on a two-dimensional gel and gives a peptide map pattern very similar to that of actin. The three major spots of pI 7.0-8.0 yield peptide maps which are indistinguishable from one another but quite different from that of actin. The membrane-bound forms of both the basic 43K protein and actin can be iodinated in a lactoperoxidase-catalyzed reaction only if the membrane vesicles are first permeabilized with saponin, a treatment which permits entry of macromolecules to the interior of the vesicles. An immunoblot of a two-dimensional gel shows that a rabbit antiserum made against alkaline extract reacts strongly with the basic 43K protein and to lesser extent with an acidic component of Mr = 55,000 but not with actin. Immunofluorescence studies have shown that this antiserum reacts with the innervated face of Torpedo electrocytes and recognizes a component of rat diaphragm muscle which is highly concentrated at the neuromuscular junction (Froehner, S.C., Gulbrandsen, V., Hyman, C., Jeng, A. Y., Neubig, R. R., and Cohen, J. B. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5230-5234). Similar experiments on intact rat muscle indicate that, like the 43K protein of Torpedo postsynaptic membranes, the immunologically related component in mammalian muscle endplates is located on the cytoplasmic side of the postsynaptic membrane.


PTHrP potentiating estradiol-induced vitellogenesis in sea bream (Sparus auratus, L.).
In fish, vitellogenin is an important nutritional precursor protein produced solely in the liver and released into the blood where it binds calcium. In the gilthead sea bream (Sparus auratus) 17beta-Estradiol (E2) plays an important role in the synthesis of vitellogenin, but also the pituitary hormones prolactin (PRL) and growth hormone (GH) can stimulate vitellogenin induction in fish. Considering the emerging involvement of PTHrP in fish calcium metabolism and the importance of calcium regulation in reproduction, we investigated the possible role of PTHrP in vitellogenesis. E2-naïve and E2-primed sea bream hepatocytes were used in an in vitro primary hepatocyte culture and stimulated with a recombinant sea bream PTHrP (sbPTHrP) to establish the contribution of sbPTHrP alone or in combination with E2 to the regulation of hepatic vitellogenin synthesis. Hepatocytes stimulated solely with sbPTHrP were not affected in their vitellogenesis. However, in hepatocytes stimulated with E2 in combination with sbPTHrP a higher vitellogenin production was seen than with E2 alone. It is concluded that sbPTHrP has a potentiating effect on estradiol stimulation of vitellogenin production by sea bream hepatocytes. The sea bream provides a unique model where vitellogenesis regulation can be studied on E2-naïve liver cells, both in vivo and in vitro.


Real time image-based air quality forecasts using a 3D-CNN approach with an attention mechanism.
This study presented an image-based deep learning method to improve the recognition of air quality from images and produce accurate multiple horizon forecasts. The proposed model was designed to incorporate a three-dimensional convolutional neural network (3D-CNN) and the gated recurrent unit (GRU) with an attention mechanism. This study included two novelties; (i) the 3D-CNN model structure was built to extract the hidden features of multiple dimensional datasets and recognize the relevant environmental variables. The GRU was fused to extract the temporal features and improve the structure of fully connected layers. (ii) An attention mechanism was incorporated into this hybrid model to adjust the influence of features and avoid random fluctuations in particulate matter values. The feasibility and reliability of the proposed method were verified through the site images of the Shanghai scenery dataset with relevant air quality monitoring data. Results showed that the proposed method has the highest forecasting accuracy over other states of art methods. The proposed model can provide multi-horizon predictions based on efficient feature extraction and good denoising ability, which is helpful in giving reliable early warning guidelines against air pollutants.


Implementing recommendations for inpatient healthcare provider encouragement of cardiac rehabilitation participation: development and evaluation of an online course.
A policy statement recommending that healthcare providers (HCPs) encourage cardiac patients to enroll in cardiac rehabilitation (CR) was recently endorsed by 23 medical societies. This study describes the development and evaluation of a guideline implementation tool. A stepwise multiple-method study was conducted. Inpatient cardiac HCPs were recruited between September 2018-May 2019 from two academic hospitals in Toronto, Canada. First, HCPs were observed during discharge discussions with patients to determine needs. Results informed selection and development of the tool by the multidisciplinary planning committee, namely an online course. It was pilot-tested with target users through a think-aloud protocol with subsequent semi-structured interviews, until saturation was achieved. Results informed refinement before launching the course. Finally, to evaluate impact, HCPs were surveyed to test whether knowledge, attitudes, self-efficacy and practice changed from before watching the course, through to post-course and 1 month later. Seven nurses (71.4% female) were observed. Five (62.5%) initiated dialogue about CR, which lasted on average 12 s. Patients asked questions, which HCPs could not answer. The planning committee decided to develop an online course to reach inpatient cardiac HCPs, to educate them on how to encourage patients to participate in CR at the bedside. The course was pilot-tested with 5 HCPs (60.0% nurse-practitioners). Revisions included providing evidence of CR benefits and clarification regarding pre-CR stress test screening. HCPs did not remember the key points to convey, so a downloadable handout was embedded for the point-of-care. The course was launched, with the surveys. Twenty-four HCPs (83.3% nurses) completed the pre-course survey, 21 (87.5%) post, and 9 (37.5%) 1 month later. CR knowledge increased from pre (mean = 2.71 ± 0.95/5) to post-course (mean = 4.10 ± 0.62; p ≤ .001), as did self-efficacy in answering patient CR questions (mean = 2.29 ± 0.95/5 pre and 3.67 ± 0.58 post; p ≤ 0.001). CR attitudes were significantly more positive post-course (mean = 4.13 ± 0.95/5 pre and 4.62 ± 0.59 post; p ≤ 0.05). With regard to practice, 8 (33.3%) HCPs reported providing patients CR handouts pre-course at least sometimes or more, and 6 (66.7%) 1 month later. Preliminary results support broader dissemination, and hence a genericized version has been created ( http://learnonthego.ca/Courses/promoting_patient_participation_in_CR_2020/promoting_patient_participation_in_CR_2020EN/story_html5.html ). Continuing education credits have been secured.


Constitutive activation of Stat3alpha in brain tumors: localization to tumor endothelial cells and activation by the endothelial tyrosine kinase receptor (VEGFR-2).
Members of the normally latent family of transcription factors signal/inducers and activators of transcription (Stat) are activated in a number of human tumors and tumor-derived cell lines. In the case of Stat3, it is believed that this activation leads to the induction of survival signals as well as increased proliferation. In this study, we demonstrate that Stat3 is constitutively activated in glioma and medulloblastoma tumors and that the activated protein localizes predominantly to the tumor endothelial cells in the highly vascularized glioma tumors. Our efforts to elucidate potential mechanism(s) for this activated protein have shown that coexpression of Stat3alpha and the vascular endothelial growth factor receptor-2 (VEGFR-2) result in ligand-independent activation of Stat3alpha tyrosine phosphorylation and subsequent transcriptional activation in non-endothelial cells. We also show that activated Stat3alpha can increase transcription from the vascular endothelial growth factor (VEGF) gene. Taken together, these results suggest that the activated Stat3alpha found in brain tumors may be due to the endothelial tyrosine kinase VEGFR-2 and that Stat3alpha may play a central role in autocrine VEGF activation.


High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial.
To determine if chronic inflammation, assessed by basal high-sensitivity C-reactive protein (hs-CRP) levels, is associated with pregnancy outcomes in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Multicenter university-based randomized controlled trial. A total of 781 couples with unexplained infertility. Secondary analysis. Adjusted risk ratios of live birth, clinical pregnancy, and pregnancy loss rates by hs-CRP levels. Associations between hs-CRP levels and clinical pregnancy rates were not observed after adjustment for baseline body mass index. There were fewer live births among women with higher hs-CRP levels, although confidence intervals crossed 1.0. The risk of pregnancy loss was greater in women with increased hs-CRP levels (1-3 mg/L: risk ratio [RR], 1.67; 95% confidence interval [CI], 1.00-2.79; >3-10 mg/L: RR, 1.84; 95% CI, 1.06-3.20; and >10 mg/L: RR, 2.14; 95% CI, 1.05-4.36 compared to women with hs-CRP <1 mg/L). This investigation suggests that chronic inflammation may increase the risk of pregnancy loss but not impact the clinical pregnancy rate in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Associations between inflammation and pregnancy outcomes in women with infertility merit further investigation. clinicaltrials.gov NCT01044862.


Correlations between the instantaneous velocity gradient and the evolution of scale-to-scale fluxes in two-dimensional flow.
Using high-resolution particle tracking velocimetry and filter-space techniques, we study the links between the scale-to-scale transfer of energy and enstrophy and instantaneously rotational and straining regions as determined by the classic Okubo-Weiss parameter in a quasi-two-dimensional laboratory flow. Although the Okubo-Weiss parameter has shortcomings, we find that, when suitably conditioned, it is surprisingly a good predictor for the future evolution of the spectral fluxes. By studying Lagrangian correlation functions, we explain our findings by showing that both the spectral fluxes and the Okubo-Weiss parameter are independently correlated for long times along fluid-element trajectories and thus that any predictive capacity of the Okubo-Weiss parameter arises because it is coupled to fluid advection. Our results suggest potential strategies for forecasting in complex flows by looking for quantities with long Lagrangian correlation times.


Characterization of the endogenous enzymatic hydrolyses of Petroselinum crispum glycosides: determined by chromatography upon their sugar and flavonoid products.
The behavior of the flavonoid diglycosides, relevant constituents of parsley (Petroselinum crispum) fruit (PFr) and leaf (PLe) samples was characterized upon their enzymatic hydrolyses applying complementary liquid chromatography-ultraviolet (LC-UV) and gas chromatography mass selective (GC-MS) detections. Analyses were performed in quantitative manner, from the same extracts as a function of hydrolysis times. Both in fruit and leaf tissue extracts, in intact and in enzyme hydrolyzed ones, apigenin, chrysoeriol, their glycosides, sugars, sugar alcohols, carboxylic acids and phytosterols, in total 17 constituents were identified and quantified. Based primarily on the selective mass fragmentation properties of the trimethylsilyl (oxime) ether/ester derivatives of constituents, we confirmed several novelties to the field. (i) It was shown for the first time that in parsley tissues different types of glycosidase enzyme are active. In PFr samples, both the stepwise and disaccharide specific endogenous mechanisms were certified, quantifying simultaneously the continuous release of apigenin, chrysoeriol, 2-O-apiosyl-apiose, apiose and glucose. (ii) 2-O-Apiosyl-glucose was demonstrated as disaccharide due to its formation under derivatization conditions from parsley glycosides. (iii) Both in PFr and in PLe samples even the invertase enzyme activity was attainable: sucrose decomposition in both tissues was going on with the same intensity. Three different types of enzymatic glycosidase processes were followed with their specific hydrolysis products by means of HPLC-UV and GC-MS, simultaneously.


Asset management to support urban land and subsurface management.
Pressure on urban areas increases by demographic and climate change. To enable healthy, adaptive and liveable urban areas different strategies are needed. One of the strategies is to make better use of subsurface space and its functions. Asset management of the Subsurface (AMS) contributes to this. Asset management provides transparency of trade-offs between performance, cost and risks throughout the entire lifecycle of these assets. AMS is based on traditional asset management methods, but it does not only take man-made assets in the subsurface into account. AMS also considers the natural functions that the subsurface, including groundwater, has to offer (ecosystem services). A Dutch community of practice consisting of national and municipal authorities, a consultancy-engineering and a research institute are developing AMS in practice in order to 1) enhance the urban underground space planning (using its benefits, avoiding problems) and 2) use, manage and maintain the (urban) subsurface and its functions. The method is currently still under development.


Atypical effect of temperature tuning on the insertion of the catalytic iron-sulfur center in a recombinant [FeFe]-hydrogenase.
The expression of recombinant [FeFe]-hydrogenases is an important step for the production of large amount of these enzymes for their exploitation in biotechnology and for the characterization of the protein-metal cofactor interactions. The correct assembly of the organometallic catalytic site, named H-cluster, requires a dedicated set of maturases that must be coexpressed in the microbial hosts or used for in vitro assembly of the active enzymes. In this work, the effect of the post-induction temperature on the recombinant expression of CaHydA [FeFe]-hydrogenase in E. coli is investigated. The results show a peculiar behavior: the enzyme expression is maximum at lower temperatures (20°C), while the specific activity of the purified CaHydA is higher at higher temperature (30°C), as a consequence of improved protein folding and active site incorporation.


Contribution of thermogenic mechanisms by male and female mice lacking pituitary adenylate cyclase-activating polypeptide in response to cold acclimation.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide critical to the regulation of the stress response, including having a role in energy homeostasis. Mice lacking PACAP are cold-sensitive and have impaired adrenergic-induced thermogenesis. Interestingly, Pacap null mice can survive cold housing if acclimated slowly, similar to observations in uncoupling protein 1 (UCP1)-deficient mice. We hypothesized that Pacap null mice use alternate thermogenic pathways to compensate for impaired adaptive thermogenesis when acclimated to cold. Observations of behavior and assessment of fiber type in skeletal muscles did not show evidence of prolonged burst shivering or changes in oxidative metabolism in male or female Pacap-/- mice during cold acclimation compared with Pacap+/+ mice. Despite previous work that has established impaired capacity for adaptive thermogenesis in Pacap null mice, adaptive thermogenesis can be induced in mice lacking PACAP to support survival with cold housing. Interestingly, sex-specific morphological and molecular differences in adipose tissue remodeling were observed in Pacap null mice compared with controls. Thus, sexual dimorphisms are highlighted in adipose tissue remodeling and thermogenesis with cold acclimation in the absence of PACAP.NEW & NOTEWORTHY This manuscript adds to the literature of endocrine regulation of adaptive thermogenesis and energy balance. It specifically describes the role of pituitary adenylate cyclase-activating polypeptide on the regulation of brown adipose tissue via the sympathetic nervous system with a focus on compensatory mechanisms of thermogenesis. We highlight sex-specific differences in energy metabolism.


Baseline White Matter Hyperintensities and Hippocampal Volume are Associated With Conversion From Normal Cognition to Mild Cognitive Impairment in the Framingham Offspring Study.
We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up. Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified. Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion from normal cognition to MCI at 6.5-year follow-up. Annualized change rates in total cerebral brain volume and hippocampal volume were associated with conversion from normal cognition to MCI to follow-up. Baseline WMH and hippocampal volume are markers that are both associated with conversion from normal cognition to MCI, highlighting the role of both vascular lesions and neurodegeneration in MCI.


Behavior: Local Lateral Habenula Interneurons Mediate Aggression.
A recent study has shown that local inhibitory GAD2-positive neurons regulate the activity of lateral habenula neurons, thereby governing aggressive behavior in male mice.


Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation.
The primate amygdala is a complex consisting of over a dozen nuclei that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. These functions are implemented through distinct connectivity profiles, which have been documented in animals but remain largely unknown in humans. Here we present results from 25 neurosurgical patients who had concurrent electrical stimulation of the amygdala with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), or fMRI (electrical stimulation fMRI; es-fMRI), methods providing strong inferences about effective connectivity of amygdala subdivisions with the rest of the brain. We quantified functional connectivity with medial and lateral amygdala, the temporal order of these connections on the timescale of milliseconds, and also detail second-order effective connectivity among the key nodes. These findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.


Body distribution of trace elements in black-tailed gulls from Rishiri Island, Japan: age-dependent accumulation and transfer to feathers and eggs.
Body distribution and maternal transfer of 18 trace elements (V, Cr, Mn, Co, Cu, Zn, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Hg, Tl, and Pb) to eggs were examined in black-tailed gulls (Larus crassirostris), which were culled in Rishiri Island, Hokkaido Prefecture, Japan. Manganese, Cu, Rb, Mo, and Cd showed the highest levels in liver and kidney, Ag, Sb, and Hg in feather, and V, Sr, and Pb in bone. Maternal transfer rates of trace elements ranged from 0.8% (Cd) to as much as 65% (Tl) of maternal body burden. Large amounts of Sr, Ba, and Tl were transferred to the eggs, though maternal transfer rates of V, Cd, Hg, and Pb were substantially low. It also was observed that Rb, Sr, Cd, Cs, and Ba hardly were excreted into feathers. Concentrations of Co in liver, Ba in liver and kidney, and Mo in liver increased significantly with age, whereas Se in bone and kidney, Hg in kidney, and Cr in feather decreased with age in the known-aged black-tailed gulls (2-20 years old). It also was suggested that feathers might be useful to estimate contamination status of trace elements in birds, especially for Hg on a population basis, although the utility is limited on an individual basis for the black-tailed gulls. To our knowledge, this is the first report on the maternal transfer rate of multielements and also on the usefulness of feathers to estimate contamination status of Hg in birds on a population basis.


Designing Well-Being: A Qualitative Investigation of Young Patients' Perspectives on the Material Hospital Environment.
Physical surroundings of healthcare facilities are suggested to influence young patients' well-being and hospitalization experiences. The current research seeks to understand young patients' views and perspectives of the hospital lobby and inpatient rooms. Thus, a qualitative study was carried out in a social pediatric clinic for young patients with disabilities, developmental delays, behavioral problems, and chronic health conditions, that is undergoing reconstruction. Operating from a critical realist position, the study employed arts-based methods in conjunction with semi-structured interviews. The data were explored by employing thematic analysis. 37 young people between the age of four and 30 years participated in the study. The analysis illustrates that the built environment should contain comforting and joyful elements, while enabling patients' autonomy. The ideal lobby was depicted as open and accessible and an ideal patient room as practical and adapted to personal needs. It is suggested that disabling and medicalized spatial arrangements and features may restrict young people's sense of control and autonomy, while possibly posing a barrier to a health-promoting environment. Large and open spaces with comforting and distracting features are cherished by patients and may be embedded in a comprehensive, yet simple overall design and structural concept.


A qualitative analysis investigating competence assessment of undergraduate nursing students.
This study reports on the process of competence assessment in undergraduate nursing programmes in New Zealand. To identify current competence assessment practice and determine how competence assessment is constructed in order to reflect student development. This research utilised a qualitative exploratory-descriptive design. Nurse educators from nine tertiary institutions opted to participate in the research. Semi-structured interviews were conducted and data were analysed using a thematic analysis approach. Three themes are reported in this article; clinical assessment pedagogy, measure of competence, and relational assessment practice. There was significant variation between and within institutions in conducting competence assessment while scaffolding competence assessment throughout the degree programme was highlighted as a challenge. This study highlights the need for an assessment process that allows for the developing competence of nursing students and competencies that are designed to adequately assess students in each year of the nursing programme.


Electrographic manifestation of drowsiness in the isolated cat cortex.
Electrical activity of the neuronally isolated cortex during waking and the onset of sleep was investigated in experiments on freely behaving cats. The transition from wakefulness to sleep is accompanied in the isolated cortex by the appearance of a stage of drowsiness, accompanied by corresponding changes in the electrocorticogram of the isolated hemisphere. The electrographic manifestation of the stage of drowsiness in the isolated cortex depends on the time elapsing after the operation and it is most marked in the late period after isolation of the cortex.


Immunopathobiology and therapeutic targets related to cytokines in liver diseases.
Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma. The progression of liver disease is controlled by a variety of factors, including liver injury, inflammatory cells, inflammatory mediators, cytokines, and the gut microbiome. In the current review, we discuss recent data on a large number of cytokines that play important roles in regulating liver injury, inflammation, fibrosis, and regeneration, with a focus on interferons and T helper (Th) 1, Th2, Th9, Th17, interleukin (IL)-1 family, IL-6 family, and IL-20 family cytokines. Hepatocytes can also produce certain cytokines (such as IL-7, IL-11, and IL-33), and the functions of these cytokines in the liver are briefly summarized. Several cytokines have great therapeutic potential, and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases, which are also described.


Does robot-assisted surgery reduce leg length discrepancy in total hip replacement? Robot-assisted posterior approach versus direct anterior approach and manual posterior approach: a propensity score-matching study.
Advocates of robot-assisted technique argue that robots could improve leg length restoration in total hip replacement. However, there were few studies to compare the robot-assisted posterior approach (RPA) with conventional posterior approach (PA) THA and direct anterior approach (DAA) THA in LLD. This study aimed to determine whether robot-assisted techniques could significantly reduce LLD compared to manual DAA and manual PA. We retrospectively reviewed the cohort of consecutive ONFH patients who underwent THA robot-assisted posterior, manual posterior, and manual DAA from January 2018 to December 2020 in one institution. One experienced surgeon performed all procedures. We calculated the propensity score to match similar patients in different groups by multivariate logistic regression analysis for each patient. We included confounders consisting of age at the time of surgery, sex, body mass index (BMI), and preoperative LLD. Postoperative LLD and Harris hip scores (HHS) at two years after surgery of different cohorts were compared. We analyzed 267 ONFH patients treated with RPA, DAA, or PA (73 RPA patients, 99 DAA patients, and 95 PA patients). After propensity score matching, we generated cohorts of 40 patients in DAA and RPA groups. And we found no significant difference in postoperative LLD between RPA and DAA cohorts (4.10 ± 3.50 mm vs 4.60 ± 4.14 mm, p = 0.577) in this study. The HHS at 2 years postoperatively were 87.04 ± 7.06 vs 85.33 ± 8.34 p = 0.202. After propensity score matching, we generated cohorts of 58 patients in manual PA and RPA groups. And there were significant differences in postoperative LLD between the RPA and PA cohorts. (3.98 ± 3.27 mm vs 5.38 ± 3.68 mm, p = 0.031). The HHS at 2 years postoperatively were 89.38 ± 6.81 vs 85.33 ± 8.81 p = 0.019. After propensity score matching, we generated cohorts of 75 patients in manual DAA and PA groups. And there were significant differences in postoperative LLD between the DAA and PA cohorts. (4.03 ± 3.93 mm vs 5.39 ± 3.83 mm, p = 0.031) The HHS at 2 years postoperatively were 89.71 ± 6.18 vs 86.91 ± 7.20 p = 0.012. This study found no significant difference in postoperative LLD between RPA and DAA, but we found a significant difference between RPA and manual PA, DAA and manual PA in ONFH patients. We found a significant advantage in leg length restoration in primary total hip arthroplasty with robot-assisted surgery.


[Combined PET-MRI of the abdomen].
The first fully integrated combined positron emission tomography-magnetic resonance imaging (PET-MRI) scanners have been clinically available since 2010. Large prospective studies regarding indications and diagnostic accuracy of this new modality are not yet available; however, preliminary studies have shown a higher diagnostic accuracy and confidence compared to PET-computed tomography (PET-CT) in regions where MRI is known to be superior to CT, such as the liver. The benefit of MRI in accurate lesion characterization and the additional value of diffusion-weighted imaging (DWI) as a complementary functional modality by means of the apparent diffusion coefficient (ADC) is apparent in entities with low tracer uptake (e.g. due to small size) and a decreased or absent accumulation pattern on PET.


Low-dose CT perfusion with combined use of CTP and CTP-derived coronary CT angiography at 70 kVp: validation with invasive fractional flow reserve.
To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938-0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880-0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765-0.900) alone (all p < 0.01). The mean radiation dose of the CTP examination was 3.8 ± 1.4 mSv. CTP-derived SP-CTA improved the diagnostic value of CTP. With a promising performance of myocardial ischemia detection and low radiation dose, the innovative low-dose, one-stop CTP examination is clinically feasible for patients who need to receive a myocardial perfusion assessment. • Myocardial CTP performed well in the evaluation of hemodynamically significant CAD. • CTP-derived single-phase CCTA improved the diagnostic value of CTP. • The combined use of low-dose CTP and CTP-derived CCTA at 70 kVp is clinically feasible for CAD patients who need to receive a myocardial perfusion assessment.


Adiponectin level and gene variability are obesity and metabolic syndrome markers in a young population.
Human obesity is accepted as an important risk factor for development of MetS. Adiponectin is linked to central obesity and ADIPOQ variants are promising markers for understanding the genetic base of obesity-related disorders. We performed analyses of adiponectin concentrations and ADIPOQ variants and tested their associations with obesity and MetS in young subjects of Croatian origin. Biochemical and anthropometric parameters of MetS were obtained for 149 unrelated subjects. Adiponectin levels were measured by ELISA assay. ADIPOQ -11391G>A and -11377C>G were genotyped by real-time PCR. BMI and WC, TG and GLUC showed inverse correlation, whereas HDL-C showed a positive correlation with adiponectin concentrations. For central obesity, we found association with -11377C>G and with -11391G>A polymorphisms. ADIPOQ -11377GG and -11391GA significantly increased the risk for the development of central obesity (OR 5.57 and OR 3.37, respectively). Significant association was found between -11391A, -11377G allele and haplotype and increased TG. -11377C>G and -11391G>A variant were significantly associated with the incidence of MetS. C>G mutation at position -11377 significantly increased the risk of MetS development (OR = 2.93). Compared with the -11391G homozygotes, carriers of the A allele had a significantly increased risk for the development of MetS (OR = 3.15). The test of overall association showed a statistically significant correlation of MetS with -11377C>G and -11391G>A haplotypes (p = 0.008). Analysis of adiponectin concentration and ADIPOQ -11391G>A and -11377C>G gene variants may be clinically meaningful for estimation of MetS risk in a young population.


Variation in Blood Pressure Classification Using 7 Blood Pressure Estimation Protocols Among Adults in Taiwan.
Discrepancies in blood pressure (BP) estimates lead to incomparable BP assessment. To determine intraindividual discrepancies in BP estimates and classifications based on different BP estimation protocols. This cross-sectional study was a secondary analysis of data from the May Measurement Month Taiwan in 2017 and 2018, which were cross-sectional survey campaigns at pharmacies nationwide to raise awareness of high BP. Participants were volunteers aged 20 years or older. Analysis was conducted from February 2 to August 7, 2020. Pharmacist-measured sitting BP using oscillometric sphygmomanometers. A total of 7 BP estimation protocols were assessed according to the latest American College of Cardiology (ACC), Chinese Hypertension League (CHL), European Society of Cardiology (ESC), International Society of Hypertension, Japanese Society of Hypertension, and National Institute of Health and Care Excellence (NICE) hypertension guidelines, and the proposed Averaging the Lowest Two systolic readings protocol. According to BP classification schemes of ESC and ACC guidelines, intraindividual discrepancies were identified if classification inconsistencies among 7 BP estimates were present. Of 81 041 participants, 62 647 adults with 3 BP readings were included. The median (interquartile range) age was 59.0 (46.0-69.0) years, and 31 922 (51.5%) were women. The intraindividual maximum mean (SD) differences in systolic/diastolic BP estimates among the seven protocols were 4.8 (4.3)/3.3 (3.1) mm Hg. The highest prevalence of BP of 140/90 mm Hg or higher was by CHL (16 405 participants [26.2%]) and the lowest was by Averaging the Lowest Two (13 996 participants [22.3%]; P < .001); while the highest prevalence of 130/80 mm Hg or higher was by NICE (37 232 participants [59.4%]) and the lowest prevalence was by Averaging the Lowest Two (32 788 participants [52.4%]; P < .001). Compared with the other 6 estimates, Averaging the Lowest Two reclassified 7.3% to 15.8% of participants designated as 140/90 mm Hg or higher to less than 140/90 mm Hg, and 4.9% to 14.1% of those as 130/80 mm Hg or higher to less than 130/80 mm Hg. Intraindividual discrepancies in classifications occurred in 19 815 participants (31.6%) with the ESC classification and 16 401 participants (26.2%) with the ACC BP classification. Classification agreements were the lowest between NICE (κ coefficient, 0.667 [95% CI, 0.662-0.671]) and ESC protocols (κ coefficient, 0.705 [95% CI, 0.701-0.709]). This cross-sectional study of adults in Taiwan found that different BP estimation protocols led to considerable intraindividual discrepancies in BP estimates and classifications. These findings suggest that the Averaging the Lowest Two protocol is less likely to overestimate BP and could serve as a prudent recommendation for BP estimation.


Segmental neck of femur fractures: A unique case report of an ipsilateral subcapital, greater trochanteric and intertrochanteric fracture and proposed management algorithm.
Neck of femur fractures are now increasingly common in an ageing population. The management is well known and has been described in great detail. Concomitant ipsilateral segmental fractures of the neck of femur (SFNOF) however are rare and their investigation and management is poorly described. We present the surgical management of a unique and complex case of an ipsilateral subcapital, greater trochanteric and intertrochanteric fracture sustained in an 87-year-old female following a low trauma injury. This fracture configuration has not been described in the literature to date, neither has our method of reconstruction for this fracture, namely hemiarthorplasty, trochanteric stabilising plate and cerclage wires. 15 cases from 1989 to 2011 managed by 8 different fixation devices and followed up for an average of 17 months (2-58 months). There was an initial mortality rate of 13% (n=2). All associated with low energy trauma occurred in female (n=8), and most with high energy trauma occurred in males (83%; n=5). The diagnosis was delayed or missed in 20% of cases, and the most common pattern was a concomitant undisplaced subcapital and intertrochanteric fracture (37.5%, n=6). The overall risk of avascular necrosis was 20%, with a greater risk in patients greater than 65 years of age (33%). Ipsilateral SFNOF are rare injuries with a bimodal distribution, and carry a greater risk of AVN. We advise that all SFNOF should have pre-operative CT planning and propose an algorithm to treat these patients with a standardised surgical approach.


The effect of improving solid waste collection on waste disposal behaviour and exposure to environmental risk factors in urban low-income communities in Pakistan.
To estimate the effect of improving waste collection services on waste disposal behaviour and exposure to environmental risk factors in urban, low-income communities in Pakistan. We enrolled six low-income communities in Islamabad (Pakistan), four of which received an intervention consisting of a door-to-door low-cost waste collection service with centralised waste processing and recycling sites. Intervention communities underwent community-level and household-level mobilisation. The effect of the intervention on waste disposal behaviour, exposure to waste and synanthropic fly counts was measured using two cross-sectional surveys in 180 households per community. Intervention communities had less favourable socio-economic indicators and poorer access to waste disposal services at baseline than control communities. Use of any waste collection service increased from 5% to 49% in the intervention communities (difference 44%, 95% CI 41%, 48%), but the increase was largely confined to two communities where post-intervention coverage exceeded 80% and 90%, respectively. An increase in the use of waste collection services was also found in the two control communities (from 21% to 67%, difference 47%, 95% CI 41%, 53%). Fly counts decreased by about 60% in the intervention communities (rate ratio 0.4, 95% CI 0.3, 0.4) but not in the control communities (rate ratio 1.52, 95% CI 1.1, 2.2). The decrease in fly counts was largely confined to the two high-coverage intervention communities. Introduction of a low-cost waste collection service has the potential for high uptake in low-income communities and for decreasing the exposure to waste and synanthropic flies at household level. Intervention success was constrained by low uptake in half of the intervention communities.


Supraspinatus pathology on MRI is associated with degree of weakness on dynamic clinical strength testing.
To analyze shoulder strength and function in patients presenting with possible supraspinatus pathology and to ascertain if these clinical findings are associated with severity of supraspinatus pathology on MRI. In total, 171 patients with presumptive rotator cuff pathology and with preserved strength on standard rotator cuff examination were prospectively recruited. Patients were subjected to bilateral shoulder strength testing employing dynamometry; this included isometric strength testing at 90° of abduction, followed by eccentric assessment of isotonic strength from full abduction through the full range of motion until the arm rested at the patient's side. We calculated absolute strength and symptomatic-to-asymptomatic arm (S/A) strength ratios. On subsequent shoulder MRI, supraspinatus pathology was designated into one of seven categories. The association between strength measurements and MRI findings was analyzed. Increasing lesion severity on MRI was associated with both decreasing absolute strength (no tear [59.9 N] to full-thickness tear [44.2 N]; P = 0.036) and decreasing S/A strength ratios during isotonic testing (no tear [91.9%] to full-thickness tear [65.3%]; P = 0.022). In contrast, there were no significant relationships between imaging severity and absolute strength or S/A strength ratios on isometric testing. Severity of supraspinatus pathology on MRI was associated with dynamic clinical function. These results validate the clinical correlation between MRI designations of supraspinatus pathology and function and suggest the need for future work to investigate utility of dynamic (versus isometric) rotator cuff physical examination maneuvers.


A note on the application of Morse theory to the study of the potential extrema of body surface potential maps.
The entire body may be approximated with a closed surface having the homotopy type of a sphere. The Morse inequalities then yield certain relationships between the local potential extrema and the saddle points appearing on body surface potential maps (BSPMs). In particular, a list of possible extremal configurations is presented.


The effect of roughness on biophysical stimuli at the bone-cartilage interface.
Numerical simulations are often used to investigate the effect of mechanical environment on fracture healing. Although these models exhibit biologically relevant mechanical parameters at the bone-callus interface, this interface is modelled as perfectly smooth when in fact it is rough. In this study, a macro-micro-two-scale finite element model was used to determine if roughness significantly alters calculated local mechanical parameters. An idealized fracture healing poroelastic model with a small micro-modelled sub-domain of cartilaginous callus adjacent to rough bone was subjected to cyclic loading. The shear stress, tangential fluid velocity, and pore pressure were investigated. With roughness similar to that at the growth plate, solid matrix shear stress differed substantially with interface roughness, whereas interstitial fluid velocity and pore pressure were only slightly affected. Hence, when modelling local micro-mechanical environments near hard-soft tissue interfaces, interface roughness should be considered.


"It Changed How I Think"-Impact of Programmatic Assessment Upon Practicing Physicians: A Qualitative Study.
Programmatic assessment is a systematic approach used to document and assess learner performance. It offers learners frequent formative feedback from a variety of contexts and uses both high- and low-stakes assessments to determine student progress. Existing research has explored learner and faculty perceptions of programmatic assessment, reporting favorable impact on faculty understanding of the importance of assessment stakes and feedback to learners while students report the ability to establish and navigate towards goals and reflect on their performance. The Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University adopted programmatic assessment methods at its inception. With more than 18 years' experience with programmatic assessment and a portfolio-based assessment system, CCLCM is well-positioned to explore its graduates' perceptions of their programmatic assessment experiences during and after medical school. In 2020, the investigators interviewed 26 of the 339 physician graduates. Participants were purposefully sampled to represent multiple class cohorts (2009-2019), clinical specialties, and practice locations. The investigators analyzed interview transcripts using thematic analysis informed by the frameworks of self-determination theory and professional identity formation. The authors identified themes and support each with participant quotes from the interviews. Based on findings, the investigators compiled a series of recommendations for other institutions who have already or plan to incorporate elements of programmatic assessment into their curricula. The authors concluded by discussing future directions for research and additional avenues of inquiry.


Development of lateral flow assay combined with recombinase polymerase amplification for highly sensitive detection of Dickeya solani.
Dickeya solani, one of the most significant bacterial pathogens, infects potato plants, resulting in severe economic damage. In this study, a lateral flow assay (LFA) combined with isothermal DNA amplification was developed for rapid, specific, and sensitive diagnosis of the potato blackleg disease caused by D. solani. Recombinase polymerase amplification (RPA) was chosen for this purpose. Five primer pairs specific to different regions of the D. solani genome were designed and screened. A primer pair providing correct recognition of the target sequence was aligned with the SOL-C region specific to D. solani and flanked by fluorescein (forward primer) and biotin (reverse primer). Lateral flow test strips were constructed to detect DNA amplicons. The RPA-LFA demonstrated a detection limit equal to 14,000 D. solani colony-forming units per gram of potato tuber. This assay provided sensitivity corresponding to the polymerase chain reaction (PCR) but was implemented at a fixed temperature (39 °C) over 30 min. No unspecific reactions with Pectobacterium, Clavibacter, and other Dickeya species were observed. Detection of latent infection of D. solani in the potato tubers by the developed RPA-LFA was verified by PCR. The obtained results confirmed that RPA-LFA has great potential for highly sensitive detection of latent infection.


The diagnosis of cerebral atrophy on the basis of cerebral angiogram.
An increased distance between brain surface, represented by the terminal arterial branches, and skull causes the appearance of a broad avascular band in the carotid angiogram, which--apart from other criteria--has been valued as a sign of cerebral atrophy. We investigated 54 patients (ages 60-79 years) suffering from cerebrovascular disease. Carotid angiographies of the afflicted hemispheres were carried out within 4 to 90 days after the stroke. The distance between vessels and skull was measured in frontal and lateral projection. We evaluated statistically the impact on this distance of alterations in extracranial vessel walls, number of attacks, severity of stroke, and patient's age. The results are compared to those of CAT. Only limited correlations have been found between the above-mentioned parameters and the distance between vessels and skull. Thus the distance is only of limited diagnostic value for the verification of senile cerebral atrophy on a vascular basis.


Pregnancy-associated-cancer in the French West Indies (Martinique): maternal and neonatal outcomes.
The management of pregnancy-associated-cancer (PAC) requires epidemiological evaluation of the pathways of care. The aim of this study was to describe maternal and neonatal outcomes of PAC in Martinique. A retrospective study was conducted using data from medical records and the Martinique Cancer Registry for all PAC diagnosed between 1st January 2000 and 31st December 2014. Eighteen women were diagnosed with PAC: 17 during pregnancy and one during the postpartum period. Mean age at diagnosis was 35.7 ± 5.4 years. PAC were mainly gynecological cancers (12/18); the other sites were: lymphoma, brain, liver, colon, skin and unknown primary site. In most cases, PAC was detected in symptomatic individuals (72.2%). Nine women had nodal involvement or initial metastasis at diagnosis. No chemotherapy was administered in cases of preservation of pregnancy. Seven fetal losses caused by abortion and miscarriage were recorded, and 11 women conducted viable pregnancies. The main neonatal pathology observed was prematurity (58.3%). Cancer management during pregnancy is a challenge for French West-Indies territories. A Caribbean Observatory of rare cancers could help to ensure a coordinated approach to support and monitoring for these patients.


Closing forces of the bovine teat canal.
The magnitude of the forces causing closure of the bovine teat canal was estimated by measuring the pressure required to cause retrograde flow of milk into the canal from a manometer attached to the external teat orifice. Before milking, the hydrostatic pressure required to cause retrograde flow was 12 kPa or greater. Retrograde flow occurred at a pressure of 4-6 kPa once the teat canal surface had been wetted. This 2- or 3-fold fall in the closing forces presumably resulted from the combined effects of fracturing the teat canal epithelium and loss of initial resting tension in the smooth muscle fibres surrounding the teat canal. After milking, retrograde flow into any teat canal occurred at a pressure approximately 1 kPa lower than the wetted, pre-milking value. This small drop, and subsequent recovery approximately 30 min after milking, reflects the change in tonicity of the smooth muscle fibres which are stretched during milking. At hydrostatic pressures below 7-9 kPa, retrograde flow could be arrested momentarily by the occurrence of a teat contraction. At 4-7 kPa, the wave of contraction was also capable of expelling 4-14 microliters milk from the teat canal indicating the outwardly directed, peristaltic nature of the phasic muscular activity.