The effects of a transition between local and global processing on vigilance performance.
Sixty participants performed a sustained attention task in which they were required to perform either global or local feature discrimination. Two groups required just one type of discrimination, while the remaining two groups started on one type of discrimination before transitioning to the other type halfway through. A transition resulted in worse performance when compared to no transition. It was also found that the local discrimination group showed improved performance over time compared to the global discrimination group. Functional near-infrared spectroscopy (fNIRS) was used to measure blood oxygenation during the task and was used as an index of cerebral hemodynamic activity. Total oxygenation was found to increase more in global discrimination tasks. It was also found that the left prefrontal cortex showed little change in nontransition tasks while in transition tasks it followed the same trend as the right prefrontal cortex. Combined with performance data, it suggests that an increased utilization of bilateral resources may in some cases improve performance over time.


Epigenetic modifiers DNMT3A and BCOR are recurrently mutated in CYLD cutaneous syndrome.
Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. Here, we comprehensively profile the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families and discover recurrent mutations in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumors suggest that isoform-specific DNMT3A2 mutations are associated with dysregulated methylation. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumors. These findings contribute to existing paradigms of cutaneous tumorigenesis and metastasis.


Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma (BHP RCC): A Distinctive Neoplasm Associated With Somatic NF2 Mutations.
We report 8 cases of a distinctive, previously undescribed renal cell carcinoma associated with somatic mutations in the neurofibromin 2 (NF2) gene. All patients were adults, ranging from 51 to 78 years of age and of cases of known sex 6 of 7 were males. The carcinomas were predominantly unencapsulated, and all had a rounded, nodular interface with the native kidney. The neoplasms were all solid with papillary architecture evident in most cases (7/8), while 1 was only tubular. All cases were biphasic, characterized by larger and smaller carcinoma cells. The smaller cells clustered around basement membrane material similar to the characteristic pattern of the t(6;11) renal cell carcinoma associated with TFEB gene fusions. In 6 of 8 carcinomas, branching nodules of small cells clustered around basement membrane material within larger acini yielding a distinctive glomeruloid pattern. In 6 of 8 carcinomas, the small cells were focally spindle-shaped and unassociated with the basement membrane material. The stroma was sclerotic in all 8 carcinomas, and all 8 contained psammoma bodies that were abundant in 2. In some carcinomas, focal or predominant areas had a less distinctive appearance; 2 had areas that resembled clear cell renal cell carcinoma, 2 had high-grade eosinophilic areas, while 1 had branching tubular architecture that resembled mucinous tubular and spindle cell carcinoma. Two carcinomas demonstrated cellular necrosis. Although we have minimal clinical follow-up, 1 case presented with distant metastasis, progressed and resulted in patient death. While NF2 mutations may be found in other established renal cell carcinoma subtypes (often as secondary genetic alterations), they are potentially the genetic driver of this distinctive entity.


Regional comparison of midwall segment and area shortening in the canine left ventricle.
We used ultrasonic segment length gauges to examine the regional behavior of midwall fibers at different sites around the left ventricular minor axis in 12 anesthetized dogs. In six dogs (group I) with circumferentially oriented midwall gauges, significantly greater shortening of anterior than lateral or posterior wall segments was demonstrated over a range of left ventricular end-diastolic pressures from 2 to 18 mm Hg. Normalized end-diastolic segment lengths increased more in the anterior wall as end-diastolic pressure increased, suggesting that regional differences in diastolic distensibility may in part account for the observed shortening differences. To examine the extent to which shortening of longitudinally oriented fibers of the subendocardium and subepicardium might influence the behavior of the midwall circumferential fibers, we implanted mutually perpendicular midwall gauges circumferentially and longitudinally in the anterior and posterior walls in six dogs (group II). Longitudinal shortening of midwall fibers was negligible at low end-diastolic pressures, but increased significantly at higher end-diastolic pressures. In the anterior wall, there was greater circumferential than longitudinal shortening, whereas, in the posterior wall, shortening was similar in the two directions. Finally, we calculated the midwall area subtended by the mutually perpendicular gauges and found the systolic change in midwall area to be similar for the anterior and posterior walls at all end-diastolic pressures. We conclude that midwall fibers demonstrate considerable nonuniformity of contraction at different sites around the minor axis. This finding may be related in part to regional differences in diastolic distensibility or in functional interactions between fiber layers. Despite these complex regional, directional, and volume dependent differences in midwall segment function, the systolic changes in midwall area did not vary regionally. Thus, different midwall sites around the minor axis circumference appear to have similar overall contributions to the ejection of blood.


Association between Atopic Dermatitis and the Metabolic Syndrome: A Systematic Review.
Atopic dermatitis (AD) may be associated with the metabolic syndrome and by that carry an increased risk of cardio-vascular disease. Our objective was to provide an update on current knowledge of the association between AD and metabolic syndrome, including each component of the metabolic syndrome. A systematic literature review was performed to identify studies investigating the association between metabolic syndrome and AD from PubMed, Embase, and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 14 studies, investigating the association between AD and the metabolic syndrome or AD and components of metabolic syndrome fulfilled the inclusion criteria and were included. It seems unlikely that the association between AD and metabolic syndrome is causal. However, women with AD tended to have components of metabolic syndrome more often than women without AD. There was a positive association between AD and central obesity measured as waist circumference, and this association was stronger for women than men. Despite conflicting results regarding hypertension, the association between hypertension and AD also appeared stronger for women. On the other hand, the association between AD and hyperglycemia appears unlikely, and the association between AD and cholesterol levels was inconsistent. In conclusion, it remains unclear whether AD is a risk factor for metabolic syndrome and its components. However, data indicate that central obesity is associated with AD and that the association is stronger for women than men.


The performance of a component-based allergen microarray for the diagnosis of kiwifruit allergy.
Allergy to kiwifruit is increasingly reported across Europe. Currently, the reliability of its diagnosis by the measurement of allergen-specific IgE with extracts or by skin testing with fresh fruits is unsatisfying. To evaluate the usefulness of a component-based allergen microarray for the diagnosis of kiwifruit allergy in a large group of patients. With an allergen microarray, we measured specific IgE and IgG4 levels to a panel of nine kiwifruit allergens in sera of 237 individuals with kiwifruit allergy. Sera from 198 allergic patients without kiwifruit allergy served as controls. Furthermore, we determined the extent of sensitization to latex. The panel of kiwifruit allergens showed a diagnostic sensitivity of 66%, a specificity of 56% and a positive predictive value of 73%. Sera from kiwifruit-allergic patients contained significantly more frequently Act d 1-specific IgE than sera from control patients. Furthermore, 51% of the positive sera contained IgE directed to a single allergen, namely Act d 1 (45%), Act d 9 (27%) or Act d 7 (13%). Within the control group, 36% sera recognized a single allergen. Out of those, 48% were positive to the cross-reactive glycoallergen Act d 7, 43% to the profilin Act d 9 and only 5% to Act d 1. Allergen-specific IgG4 levels did not differ between kiwifruit-allergic and -tolerant patients. Kiwifruit- and latex-allergic patients contained Hev b 11-specific IgE significantly more frequently than latex-allergic patients without kiwifruit allergy. Act d 1 can be considered a marker allergen for genuine sensitization to kiwifruit. We demonstrated that a component-based kiwifruit allergen microarray would improve the prognostic value of in vitro diagnostic tests.


Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations.
Transforming activity of the c-ret proto-oncogene with multiple endocrine neoplasia (MEN) 2A mutations was investigated by transfection of NIH 3T3 cells. Mutant c-ret genes driven by the simian virus 40 or cytomegalovirus promoter induced transformation with high efficiencies. The 170-kDa Ret protein present on the cell surface of transformed cells was highly phosphorylated on tyrosine and formed disulfide-linked homodimers. This result indicated that MEN 2A mutations induced ligand-independent dimerization of the c-Ret protein on the cell surface, leading to activation of its intrinsic tyrosine kinase. In addition to the MEN 2A mutations, we further introduced a mutation (lysine for asparaginic acid at codon 300 [D300K]) in a putative Ca(2+)-binding site of the cadherin-like domain. When c-ret cDNA with both MEN 2A and D300K mutations was transfected into NIH 3T3 cells, transforming activity drastically decreased. Western blot (immunoblot) analysis revealed that very little of the 170-kDa Ret protein with the D300K mutation was expressed in transfectants while expression of the 150-kDa Ret protein retained in the endoplasmic reticulum was not affected. This result also demonstrated that transport of the Ret protein to the plasma membrane is required for its transforming activity.


DNA and protein components of nuclear acceptor sites for androgen receptors in the rat prostate.
Androgen receptor-acceptor complexes in nuclei from rat ventral prostates were cross-linked in situ with formaldehyde and partially purified using affinity chromatography. To isolate acceptor DNA, the cross-linked receptor-acceptor complexes in formaldehyde-treated chromatin samples were adsorbed to dihydrotestosterone-17 beta-succinyl agarose, eluted with 75 microM dihydrotestosterone-1% SDS, digested with proteinase K and extracted with phenol-chloroform. After 32P end-labelling and PAGE, this DNA contained two distinct bands of DNA (about 300 and 400 base pairs respectively) which were unique relative to the total prostatic DNA. As an alternative approach for characterizing acceptor DNA, the DNA in prostatic nuclei and cross-linked chromatin was labelled with 32P by nick translation and analysed in glycerol density gradients for associations with cross-linked androgen receptors. A symmetrical 7s peak of 32P-DNA with a small amount of coincident receptor was observed in the gradients after mild trypsin treatment. In the absence of trypsin treatment, both the cross-linked receptors and the labelled DNA sedimented to the bottom of the gradients. Isolation of acceptor proteins involved iodination of cross-linked chromatin with 125I and androgen affinity chromatography. A comparison of the relative efficiency of retention and elution of 125I-proteins from different affinity columns revealed that testosterone-17 beta-succinyl agarose was potentially most suitable for purification of acceptor proteins. After electrophoresis on SDS-polyacrylamide gels, the eluates from this type of affinity matrix were found to contain two major peaks of 125I-labelled proteins--one corresponding to a protein with a similar molecular weight as the nuclear androgen receptor (33,000 Da); the other having a molecular weight of 20,000 Da. While the precise identity of this latter entity is unknown, its enrichment and retention by the affinity gel implies that it is closely associated with the androgen receptor and may be a component of the acceptor sites.


Development of Screening Questionnaire for Detection of Alcohol Dependence.
Alcohol dependence (AD) is a major reason for morbidity and visits to emergency medical settings. However, the detection of AD is often difficult or overlooked. This study aimed to develop a brief screening questionnaire in Hindi language for detection of AD in an emergency medical setting. The authors in consultation devised a set of questions related to AD in the Hindi language requiring binary yes/no type of response. These questions were guided by clinical experience, nosological criteria and previously published screening questionnaires. After initial piloting, these questions were administered by the treating doctors to 100 consenting adult patients presenting with possible AD in the emergency medical services of a tertiary care hospital in North India. A diagnosis of AD was arrived at by administering Mini-International Neuropsychiatric Interview separately. Identification of the most discriminant combinations of items for the detection of AD were based on the chi-square test and binary logistic regression analyses. The final version of the questionnaire was then externally validated on another cohort of patients. Based on the analyses, we retained 5 items in the final version of the questionnaire. Sensitivity and specificity values for cut-off scores were calculated. Subsequent external validation revealed satisfactory psychometric properties of the questionnaire. The questionnaire represents a simple and brief clinician-administered instrument for screening of AD in an emergency medical setting.


Tramadol for postoperative pain treatment in children.
According to current recommendations a multimodal approach is believed to be the gold standard for postoperative pain treatment in children. However, several surveys in the last few years demonstrated that postoperative pain in children is still a serious problem, mainly because opioids are avoided. One of the reasons for this is the fear of severe adverse events following opioid administration. Tramadol is a weak mu-opioid agonist and inhibits reuptake of noradrenaline and serotonin (5HT). Because of a relatively wide therapeutic window and a ceiling effect with a lower risk for severe adverse events (for example respiratory depression) tramadol is a widely used opioid in children. However, the exact efficacy and occurrence of adverse events following tramadol (in comparison with placebo or other opioids) for postoperative pain treatment in children and adolescents are currently not clear. To assess the effectiveness and side effect profile of tramadol for postoperative pain relief in children and adolescents undergoing different surgical procedures. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE via PubMed (January 1966 to July 2014) and EMBASE via Ovid (January 1947 to July 2014). There were no restrictions regarding language or date of publication. The reference lists of all included trials were checked for additional studies. All randomised controlled clinical trials investigating the perioperative administration of tramadol compared to placebo or other opioids for postoperative pain treatment in children and adolescents were included. Three review authors independently assessed the study eligibility, performed the data extraction and assessed the risk of bias of included trials. Twenty randomised controlled trials involving 1170 patients were included in this systematic review. The overall risk of bias in included trials was assessed as unclear, because concealment of allocation processes and blinding of outcome assessors were poorly described. Due to inconsistent outcome reporting, data from 17 included trials could be pooled for some endpoints only. Eight trials compared tramadol administration with placebo and five trials found that the need for rescue analgesia in the postoperative care unit (PACU) was reduced in children receiving tramadol (RR 0.40; 95% CI 0.20 to 0.78; low quality evidence). Only one trial investigated the number of patients with moderate to severe pain, but a non-validated pain scale was used (very low quality evidence). Four trials compared morphine with tramadol administration. There was no clear evidence of difference in the need for rescue analgesia in the PACU (RR 1.25; 95% CI 0.83 to 1.89; low quality evidence) with tramadol compared with morphine. No trials could be pooled for the outcome 'number of patients with moderate to severe pain'. Three trials were included for the comparison of tramadol with nalbuphine. There was no clear evidence for the need for rescue analgesia in the PACU (RR 0,63; 95% CI 0.16 to 2.45; low quality evidence). Only one trial reported the number of patients with moderate to severe pain, but used a non-validated pain scale (very low quality evidence). Two out of six included trials, which compared pethidine with tramadol, reported the number of children with a need for rescue analgesia within the PACU and showed no clear evidence (RR 0.93; 95% CI 0.43 to 2.02; very low quality evidence). Two trials reported the number of patients with moderate to severe pain and showed a lower RR in patients treated with tramadol (RR 0.64; 95% CI 0.36 to 1.16; low quality evidence). Only one trial was included, which compared tramadol with fentanyl, reporting the number of patients with the need for rescue analgesia (very low quality evidence). Generally, adverse events were poorly reported. Most data could be pooled for the comparison with placebo focusing on the RR for postoperative nausea and vomiting (PONV) in the postoperative care unit and 24 h postoperation. Children treated with tramadol, compared to placebo, did not show clear evidence of benefit for PONV in the postoperative care unit (RR 0.84; 95% CI 0.28 to 2.52; moderate quality evidence) and 24 h postoperation (RR 0.78; 95% CI 0.54 to 1.12; moderate quality evidence). The overall evidence regarding tramadol for postoperative pain in children is currently low or very low and should be interpreted with caution due to small studies and methodological problems (different validated and non-validated pain scales with different pain triggers, missing sample size calculations and missing intention-to-treat analysis). Nevertheless, we demonstrated that tramadol administration might provide appropriate analgesia when compared to placebo; this is based on results showing reduced rescue analgesia in children treated with tramadol compared to placebo. In contrast, the evidence regarding the comparison with other opioids (for example morphine) was uncertain. Adverse events were only poorly reported, so an accurate risk-benefit analysis was not possible.


Primary Malignant Melanoma of the Esophagus: A Case Report and Review of the Literature.
BACKGROUND Primary malignant melanoma of the esophagus (PMME) is a rare cancer with a poor prognosis. It is often difficult to differentiate from non-epithelial malignant tumors, and immunohistochemical staining may be needed to diagnose the condition. The mainstay of treatment is usually surgical with curative or palliative intent, since radio- and chemotherapy do not really improve the outcome. The average survival rate after surgery is 34.5 months. At the time of diagnosis, 40-80% of cases have local regional lymph node metastases. CASE REPORT The case of a 67-year-old male patient with PMME is reported. He presented with progressive dysphagia. A computerized tomography was performed in which a polypoid mass was observed in the distal esophagus. It was originally suspected to be an adenocarcinoma, but was subsequently correctly diagnosed by immunohistochemical staining with HMB-45 antibody and by the presence of S-100 protein. A subtotal esophagectomy was performed. CONCLUSIONS Very few cases of PMME have been reported in the literature and there is only limited clinical experience with this disease. Therefore, it is very difficult to establish clear criteria for clinical recognition of this type of melanoma. Early histopathological confirmation of the character is essential for further treatment in case of confirmation of malignancy.


Use of ecosystem services economic valuation for decision making: questioning a literature blindspot.
Ecosystem Services economic Valuation (ESV) is often seen as a tool that can potentially enhance our collective choices regarding ecosystem services as it factors in the costs and benefits of their degradation. Yet, to achieve this, the social processes leading to decisions need to use ESV effectively. This makes it necessary to understand if and how ESV is or is not used by decision-makers. However, there appears to be a literature blindspot as to the issue of the Use of Ecosystem Services economic Valuation (UESV). This paper proposes a systematic review on UESV in peer-reviewed scientific literature. It shows that this literature gives little attention to this issue and rarely reports cases where ESV has been put to actual use, even though such use is frequently referred to as founding the goal and justification of ESV. The review identifies three categories of potential UESV: decisive, technical and informative, which are usually mentioned as prospects for the valuations published. Two sets of hypotheses are examined to explain this result: either the use of ESV is a common practice, but is absent from the literature reviewed here; or the use of ESV is effectively rare. These hypotheses are discussed and open up further avenues of research which should make the actual use of ESV their core concern.


Results of root canal treatment in dogs: 127 cases (1995-2000).
To evaluate results of root canal treatment in dogs. Retrospective study. 127 tooth roots in 64 dogs. Radiographs obtained before surgery, immediately after surgery, and during follow-up examinations after surgery were evaluated by 2 individuals. Treatment was considered successful if the periodontal ligament space was normal and possible preoperative root resorption, if present, had ceased. Treatment was considered to show no evidence of failure if possible preoperative root resorption had ceased but a preexisting periapical lesion had remained the same or only decreased in size and not complete resolved. Treatment was considered to have failed if a periapical lesion or root resorption developed subsequent to endodontic treatment, if a preexisting periapical lesion had increased in size, or if possible preoperative root resorption appeared to continue after endodontic treatment. Follow-up time ranged from 1 to 60 months (mean, 13 months). Treatment was classified as successful for 87 (69%) roots, as showing no evidence of failure for 33 (26%) roots, and as having failed for 7 (6%) roots. The success rate was lower for canine teeth than for maxillary fourth premolar teeth. Roots with a preexisting periapical lucency or preexisting root resorption had lower success rates. The use of intracanal medication and the method and quality of obturation were not associated with outcome. Results suggest that root canal treatment offers a viable option for salvage of periodontally sound but endodontically diseased teeth in dogs.


A web-based telemedicine system for low-resource settings 13 years on: insights from referrers and specialists.
One way to tackle health inequalities in resource-poor settings is to establish links between doctors and health professionals there and specialists elsewhere using web-based telemedicine. One such system run by the Swinfen Charitable Trust has been in existence for 13 years which is an unusually long time for such systems. We wanted to gain some insights into whether and how this system might be improved. We carried out a survey by questionnaire of referrers and specialists over a six months period. During the study period, a total of 111 cases were referred from 35 different practitioners, of whom 24% were not doctors. Survey replies were received concerning 67 cases, a response rate of 61 per cent. Eighty-seven per cent of the responding referrers found the telemedicine advice useful, and 78% were able to follow the advice provided. As a result of the advice received, the diagnosis was changed in 22% of all cases and confirmed in a further 18 per cent. Patient management was changed in 33 per cent. There was no substantial difference between doctors and non-doctors. During the study period, the 111 cases were responded to by 148 specialists, from whom 108 replies to the questionnaire were received, a response rate of 73 per cent. About half of the specialists (47%) felt that their advice had improved the management of the patients. There were 62 cases where it was possible to match up the opinions of the referrer and the consultants about the value of a specific teleconsultation. In 34 cases (55%) the referrers and specialists agreed about the value. However, in 28 cases (45%) they did not: specialists markedly underestimated the value of a consultation compared to referrers. Both referrers and specialist were extremely positive about the system which appears to be working well. Minor changes such as a clearer referral template and an improved web interface for specialists may improve it.


Repair of topoisomerase-mediated DNA damage in bacteriophage T4.
Type II topoisomerase inhibitors are used to treat both tumors and bacterial infections. These inhibitors stabilize covalent DNA-topoisomerase cleavage complexes that ultimately cause lethal DNA damage. A functional recombinational repair apparatus decreases sensitivity to these drugs, suggesting that topoisomerase-mediated DNA damage is amenable to such repair. Using a bacteriophage T4 model system, we have developed a novel in vivo plasmid-based assay that allows physical analysis of the repair products from one particular topoisomerase cleavage site. We show that the antitumor agent 4'-(9-acridinylamino)methanesulphon-m-anisidide (m-AMSA) stabilizes the T4 type II topoisomerase at the strong topoisomerase cleavage site on the plasmid, thereby stimulating recombinational repair. The resulting m-AMSA-dependent repair products do not form in the absence of functional topoisomerase and appear at lower drug concentrations with a drug-hypersensitive topoisomerase mutant. The appearance of repair products requires that the plasmid contain a T4 origin of replication. Finally, genetic analyses demonstrate that repair product formation is absolutely dependent on genes 32 and 46, largely dependent on genes uvsX and uvsY, and only partly dependent on gene 49. Very similar genetic requirements are observed for repair of endonuclease-generated double-strand breaks, suggesting mechanistic similarity between the two repair pathways.


Housing and Health Outcomes of persons living with HIV/AIDS (PLWHAs) in the Lower Manya Krobo District, Ghana.
Although emerging in Western industrialized societies, limited research exists on the links between housing and health outcomes for persons living with HIV/AIDS (PLWHAs) in sub-Saharan Africa (SSA). Using survey data collected from 605 PLWHAs in the Lower Manya Krobo district of Ghana, this paper examined the effects of housing structure, arrangements, accessibility and conditions on the physical and psychological/emotional health of respondents. Results indicate that housing variables have independent effects on health outcomes, controlling for socio-economic and demographic variables. Respondents living in poor housing structures and deplorable housing conditions had poorer physical and psychological health scores. The findings suggest that it is relevant to think about houses occupied by PLWHAs as important sources of health inequality.


Modelling the differential effects of prisms on perception and action in neglect.
Damage to the right parietal cortex often leads to a syndrome known as unilateral neglect in which the patient fails to attend or respond to stimuli in left space. Recent work attempting to rehabilitate the disorder has made use of rightward-shifting prisms that displace visual input further rightward. After a brief period of adaptation to prisms, many of the symptoms of neglect show improvements that can last for hours or longer, depending on the adaptation procedure. Recent work has shown, however, that differential effects of prisms can be observed on actions (which are typically improved) and perceptual biases (which often remain unchanged). Here, we present a computational model capable of explaining some basic symptoms of neglect (line bisection behaviour), the effects of prism adaptation in both healthy controls and neglect patients and the observed dissociation between action and perception following prisms. The results of our simulations support recent contentions that prisms primarily influence behaviours normally thought to be controlled by the dorsal stream.


An examination of touch between nurses and elderly patients in a continuing care setting in Northern Ireland.
The use of touch is an inherent part of nursing practice. This investigation examined the amount and type of touch received by elderly patients from nurses. It also attempted to assess elderly patients' perceptions of instrumental and expressive touch given by nurses. The Extended Model of Interpersonal Interaction formed the conceptual framework for the study. Non-participant observation and semi-structured interviews were the methods employed for data collection. Results tentatively suggest that most nurse-patient touch interactions in a care of the elderly ward are instrumental in nature. Expressive touches are predominantly given to body extremities. The gender of the nurse initiating touch and the part of the body touched influence the elderly patients' perception of the touch interaction. In particular, expressive touching behaviours by nurses that involve the leg, face and around the shoulders are perceived as uncomfortable. The only touching behaviour perceived as comfortable by all respondents was instrumental touching of the arm and shoulder by a female nurse. Elderly patients may misinterpret the goal or the motivation behind touch initiation by a nurse. Therefore, an awareness and a sensitivity towards elderly patients' needs and desires for tactile communication are required by nurses.


Acceptability and Utilization of Three Nutritional Supplements during Pregnancy: Findings from a Longitudinal, Mixed-Methods Study in Niger.
Nutritional status in pregnancy is a key determinant of birth outcomes. In low-income countries, maternal diets are often limited, and daily nutrient supplements are recommended to fill nutrient gaps. As a result, it is important to understand the factors influencing acceptability and utilization of nutrient supplements in these settings. Qualitative data (individual interviews and focus group discussions with pregnant women, household members, and study staff) and quantitative data (unannounced household spot checks) were collected in 24 villages in the Maradi region of south-central Niger. Each village was randomly assigned to one of three study arms, with pregnant women receiving either iron and folic acid (IFA) supplements, multiple micronutrient (MMN) supplements, or medium-quantity lipid-based nutrient supplements (MQ-LNS) for daily consumption during pregnancy. Data were collected longitudinally to capture changes in perspective as women progressed through their pregnancy. Participants accepted all three supplement types, and perceived a wide range of health benefits attributed to supplement consumption. However, several important barriers to appropriate consumption were reported, and rumors about the supplements leading to childbirth complications also decreased utilization. The household spot checks suggested that IFA had the highest level of correct consumption. Overall, despite a stated high level of acceptance and enthusiasm for the supplements among participants and their household members, certain fears, side effects, and organoleptic factors led to decreased utilization. The effectiveness of future programs to improve maternal nutritional status through supplementation may be improved by understanding perceived barriers and facilitating factors among participants and tailoring communication efforts appropriately.


Study protocol: use of a smartphone application to support the implementation of a complex physical activity intervention (+Stay Active) in women with gestational diabetes mellitus-protocol for a non-randomised feasibility study.
Physical activity (PA) interventions have a promising role in the management of gestational diabetes mellitus (GDM). Digital technologies can support PA at scale and remotely. The protocol describes a study designed to determine the feasibility and acceptability of a complex intervention; known as +Stay Active. +Stay Active combines motivational interviewing with a bespoke behaviour change informed smartphone application (Stay-Active) to augment PA levels in women with GDM. This is a non-randomised feasibility study using a mixed methods approach. Participants will be recruited from the GDM antenatal clinic at the Women Centre, John Radcliffe Hospital, Oxford. Following baseline assessments (visit 1) including self-reported and device determined PA assessment (wearing a wrist accelerometer), women will be invited to participate in an online motivational interview, then download and use the Stay-Active app (Android or iOS) (visit 2). Women will have access to Stay-Active until 36 weeks gestation, when engagement and PA levels will be reassessed (visit 3). The target sample size is 60 women. Primary outcomes are recruitment and retention rates, compliance and assessment of participant engagement and acceptability with the intervention. Secondary outcomes are assessment of blood glucose control, self-reported and device determined assessment of PA, usage and structured feedback of participant's attitudes to +Stay Active, assessment of health costs and description of maternal and neonatal outcomes. This study will provide key insights into this complex intervention regarding engagement in smartphone technology and the wearing of accelerometers. These data will inform the development of a randomised controlled trial with refinements to intervention implementation. The study has received a favourable opinion from South Central-Hampshire B Research Ethics Committee; REC reference: 20/SC/0342. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, conferences and seminar presentations. ISRCTN11366562.


Family patterns of developmental dyslexia, part II: behavioral phenotypes.
The motor control of bimanual coordination and motor speech was compared between first degree relatives from families with at least 2 dyslexic family members, and families where probands were the only affected family members. Half of affected relatives had motor coordination deficits; and they came from families in which probands also showed impaired motor coordination. By contrast, affected relatives without motor deficits came from dyslexia families where probands did not have motor deficits. Motor coordination deficits were more common and more severe among affected offspring in families where both parents were affected than among affected offspring in families where only one parent was affected. However, motor coordination deficits were also more common and more severe in affected parents when both parents were affected than among affected parents in families where only one parent was affected. We conclude that impaired temporal resolution in motor action identifies a behavioral phenotype in some subtypes of developmental dyslexia. The observed pattern of transmission for motor deficits and reading impairment in about half of dyslexia families was most congruent with a genetic model of dyslexia in which 2 codominant major genes cosegregate in dyslexia pedigrees where the proband is also motorically impaired.


SurvJamda: an R package to predict patients' survival and risk assessment using joint analysis of microarray gene expression data.
SurvJamda (Survival prediction by joint analysis of microarray data) is an R package that utilizes joint analysis of microarray gene expression data to predict patients' survival and risk assessment. Joint analysis can be performed by merging datasets or meta-analysis to increase the sample size and to improve survival prognosis. The prognosis performance derived from the combined datasets can be assessed to determine which feature selection approach, joint analysis method and bias estimation provide the most robust prognosis for a given set of datasets. The survJamda package is available at the Comprehensive R Archive Network, http://cran.r-project.org. email@example.com.


3-D ultrastructure of O. tauri: electron cryotomography of an entire eukaryotic cell.
The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes.


The paradox of conscientious objection and the anemic concept of 'conscience': downplaying the role of moral integrity in health care.
Conscientious objection in health care is a form of compromise whereby health care practitioners can refuse to take part in safe, legal, and beneficial medical procedures to which they have a moral opposition (for instance abortion). Arguments in defense of conscientious objection in medicine are usually based on the value of respect for the moral integrity of practitioners. I will show that philosophical arguments in defense of conscientious objection based on respect for such moral integrity are extremely weak and, if taken seriously, lead to consequences that we would not (and should not) accept. I then propose that the best philosophical argument that defenders of conscientious objection in medicine can consistently deploy is one that appeals to (some form of) either moral relativism or subjectivism. I suggest that, unless either moral relativism or subjectivism is a valid theory--which is exactly what many defenders of conscientious objection (as well as many others) do not think--the role of moral integrity and conscientious objection in health care should be significantly downplayed and left out of the range of ethically relevant considerations.


Occupational radiation doses among diagnostic radiation workers in South Korea, 1996-2006.
This study details the distribution and trends of doses of occupational radiation among diagnostic radiation workers by using the national dose registry between 1996 and 2006 by the Korea Food and Drug Administration. Dose measurements were collected quarterly by the use of thermoluminescent dosimeter personal monitors. A total of 61 732 workers were monitored, including 18 376 radiologic technologists (30 %), 13 762 physicians (22 %), 9858 dentists (16 %) and 6114 dental hygienists (9.9 %). The average annual effective doses of all monitored workers decreased from 1.75 to 0.80 mSv over the study period. Among all diagnostic radiation workers, radiologic technologists received both the highest effective and collective doses. Male radiologic technologists aged 30-49 y composed the majority of workers receiving more than 5 mSv in a quarter. More intensive monitoring of occupational radiation exposure and investigation into its health effects on diagnostic radiation workers are required in South Korea.


Sequence dependence on DNA photochemistry: a computational study of photodimerization pathways in TpdC and dCpT dinucleotides.
The excited states involved in the main photodimerization paths in TpdC and dCpT are mapped by PCM/TD-M052X calculations, considering different dinucleotide conformers. As for TT steps, a cyclobutane pyrimidine dimer (CPD) is formed on the PES of the lowest energy exciton, delocalized over two stacked pyrimidines; 6-4 pyrimidine-pyrimidone (64-PP) adduct's formation involves instead a 5'-ter → 3'-ter charge transfer state. For dCpT, 64-PP dimerization occurs via a two-step reaction, which proceeds through an oxetane intermediate. For TpdC, instead, the final 64-PP product is obtained in a single step and it is as stable as the CPD photoproduct, explaining the relatively large yield of 64-PP found experimentally for TC steps in DNA.


Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study.
Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment. Moreover, while it is well-known that responses to the same moral dilemmas differ across individuals, to what extent this variability may be rooted in genetics still remains to be understood. As dopamine is a key modulator of neural processes underlying executive functions, we questioned whether genetic polymorphisms associated with decision-making and dopaminergic neurotransmission modulation would contribute to the observed variability in moral judgment. To this aim, we genotyped five genetic variants of the dopaminergic pathway [rs1800955 in the dopamine receptor D4 (DRD4) gene, DRD4 48 bp variable number of tandem repeat (VNTR), solute carrier family 6 member 3 (SLC6A3) 40 bp VNTR, rs4680 in the catechol-O-methyl transferase (COMT) gene, and rs1800497 in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene] in 200 subjects, who were requested to answer 56 moral dilemmas. As these variants are all located in genes belonging to the dopaminergic pathway, they were combined in multilocus genetic profiles for the association analysis. While no individual variant showed any significant effects on moral dilemma responses, the multilocus genetic profile analysis revealed a significant gender-specific influence on human moral acceptability. Specifically, those genotype combinations that improve dopaminergic signaling selectively increased moral acceptability in females, by making their responses to moral dilemmas more similar to those provided by males. As females usually give more emotionally-based answers and engage the "emotional brain" more than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.


Why has the Universal Coverage Scheme in Thailand achieved a pro-poor public subsidy for health care?
Thailand has achieved universal health coverage since 2002 through the implementation of the Universal Coverage Scheme (UCS) for 47 million of the population who were neither private sector employees nor government employees. A well performing UCS should achieve health equity goals in terms of health service use and distribution of government subsidy on health. With these goals in mind, this paper assesses the magnitude and trend of government health budget benefiting the poor as compared to the rich UCS members. Benefit incidence analysis was conducted using the nationally representative household surveys, Health and Welfare Surveys, between 2003 and 2009. UCS members are grouped into five different socio-economic status using asset indexes and wealth quintiles. The total government subsidy, net of direct household payment, for combined outpatient (OP) and inpatient (IP) services to public hospitals and health facilities provided to UCS members, had increased from 30 billion Baht (US$ 1 billion) in 2003 to 40-46 billion Baht in 2004-2009. In 2003 for 23% and 12% of the UCS members who belonged to the poorest and richest quintiles of the whole-country populations respectively, the share of public subsidies for OP service was 28% and 7% for the poorest and the richest quintiles, whereby for IP services the share was 27% and 6% for the poorest and richest quintiles respectively. This reflects a pro-poor outcome of public subsidies to healthcare. The OP and IP public subsidies remained consistently pro-poor in subsequent years.The pro-poor benefit incidence is determined by higher utilization by the poorest than the richest quintiles, especially at health centres and district hospitals. Thus the probability and the amount of household direct health payment for public facilities by the poorest UCS members were less than their richest counterparts. Higher utilization and better financial risk protection benefiting the poor UCS members are the results of extensive geographical coverage of health service infrastructure especially at district level, adequate finance and functioning primary healthcare, comprehensive benefit package and zero copayment at points of services.


Lead exposure causes thyroid abnormalities in diabetic rats.
Lead is a widely-spread environmental pollutant and a commonly-used industrial chemical that can cause multisystemic adverse health effects. However, the effects of lead exposure on diabetic animals have not been reported so far. The aim of this study is to evaluate the effects of lead exposure on thyroid, renal and oxidative stress markers in diabetic Wistar rats. Diabetes was induced with an intraperitoneal (i.p.) injection of streptozocin (STZ). Six weeks later, rats were exposed i.p. to either distilled water (control group) or 25, 50 and 100 mg/kg of lead acetate (treatment groups). We found a positive relationship between the administered doses of lead acetate and its measured levels in blood samples (P < 0.01). Treatment of diabetic animals with lead acetate resulted in significant weight loss (P < 0.001). It also caused an increase in thyroid stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and triiodothyronine levels (P < 0.01), a clinical picture consistent with hypothyroidism. Lead acetate exposure increased urea levels (P < 0.05) and caused a significant decrease in creatinine (P < 0.05). Besides, while the concentrations of malondialdehyde were not affected, glutathione stores were depleted (P < 0.01); in response to lead exposure. In conclusion, exposure of diabetic rats to lead acetate resulted in weight loss, clinical hypothyroidism, renal damage and oxidative stress.


Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis.
Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jkappa gene, the effector of "canonical" Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch-CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.


Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval.
OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy. a detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted. similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357). the superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.


A dynamic clinical pathway for the treatment of patients with early breast cancer is a tool for better cancer care: implementation and prospective analysis between 2002-2010.
Due to increasing the complexity of breast cancer treatment it is of paramount importance to develop structured care in order to avoid a chaotic and non-consistent management of patients. Clinical pathways, a result of the adaptation of the documents used in industrial quality management namely the Standard Operating Procedures, can be used to improve efficiency and quality of care. They also aim to re-centre the focus on the patient's overall journey, rather than the contribution of each specialty or caring function independently. The effect of the implementation and prospective systematic evaluation of a clinical care pathway for the management of patients with early breast cancer in a single breast unit is evaluated over a long time interval (between 2002 and 2010). Annual analysis of predefined clinical outcome measures, service indicators, team indicators, process indicators and financial indicators was performed. Pathway quality control meetings were organized at least once a year. Systematic feedback was given to the team members, and if necessary the pathway was adapted according to evidence based literature data and in house pathway related data in order to improve quality. The annual number of patients included in the pathway (289 vs. 390, P <0.01), proportion of patients with Tis-T1 tumors (42% vs. 58%, P <0.01), negative lymph nodes (44% vs. 58%, P <0.01) and no metastases at diagnosis (91.5% vs. 95.9%) has risen significantly between 2002 and 2010. Evolution of mandatory quality indicators defined by EUSOMA shows a significant improvement of quality of cancer care. Particularly, the proportion of patients having anti-hormonal therapy (84.8% vs. 97.4%, P = 0.002) and adjuvant chemotherapy according to the guidelines (72% vs. 95.6%, P = 0.028) increased dramatically. Patient satisfaction improved significantly (P <0.05). Progression free 4-year survival was significantly higher for all patients, for T1 tumors only and for T2-T4 tumors only, treated between 2006 to 2008 compared to between 1999 to 2002 and 2003 to 2005 (P = 0.006, P = 0.05, P = 0.06, respectively). Overall 4-year survival of the entire population treated between 2006 and 2008 was significantly better (P = 0.05). Although the patient characteristics changed over the years due to better screening, this clinical pathway and regular audit of quality indicators for the treatment of patients with operable breast cancer proved to be important tools to improve the quality of care, patient satisfaction and outcome.


The cellular pathway of antigen presentation: biochemical and functional analysis of antigen processing in dendritic cells and macrophages.
The response of primed T cells to keyhole limpet haemocyanin (KLH) was used to compare the characteristics of antigen presentation by lymphoid dendritic cells, splenic and peritoneal macrophages. In a similar manner to macrophages, purified dendritic cells could be pulsed with antigen and subsequently fixed by brief glutaraldehyde fixation and still retain antigen presenting activity. Also, as previously reported for macrophages, presentation could be inhibited by chloroquine. These functional experiments suggested that the pathway of antigen presentation in dendritic cells and macrophages was similar or identical. However, biochemical studies, using radiolabelled antigen, showed that dendritic cells do not significantly degrade large proteins such as KLH to TCA-soluble form, but partially hydrolyse them to smaller peptide fragments. The significance of these results in terms of a model of the cellular pathways of antigen presentation is discussed.


VH4-34 encoded antibodies in systemic lupus erythematosus: a specific diagnostic marker that correlates with clinical disease characteristics.
To determine the clinical significance of elevated serum levels of VH4-34 encoded antibodies (VH4-34 Ab) with respect to the diagnosis and clinical characteristics of systemic lupus erythematosus (SLE). Ninety-five patients with SLE and 344 controls were studied. The controls included 34 healthy individuals, 282 patients with nonautoimmune diseases, and 28 patients with autoimmune diseases other than SLE. VH4-34 Ab levels were measured by inhibition ELISA using anti-idiotope monoclonal antibody (9G4). SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Fifty-two of 95 patients with SLE had elevated levels of VH4-34 Ab compared to 18 of 344 controls (5%), giving a sensitivity of 55% and a specificity of 95% for elevated VH4-34 Ab as a serologic test for SLE. The positive predictive value of elevated VH4-34 under these conditions was 74-85%. In this study, anti-dsDNA was not VH4-34 encoded. Significant correlations between VH4-34 and disease activity and severity indices were observed (r = 0.29-0.50). The relative risk for severe disease in SLE patients with VH4-34 antibody level in the highest tertile compared to the lowest tertile was 5.25. Twenty-five of 29 patients with lupus nephritis and 6 of 6 patients with central nervous system (CNS) lupus had elevated VH4-34 Ab. With a specificity of 94-95%, the VH4-34 antibody assay may prove valuable as a confirmatory diagnostic test for SLE. In patients with known SLE, serum VH4-34 Ab levels correlate with overall disease severity and activity, but not damage, and with nephritis and CNS lupus.


Closely related species show species-specific environmental responses and different spatial conservation needs: Prionailurus cats in the Indian subcontinent.
Phylogenetically closely related species are often assumed to have similar responses to environmental conditions, but species-specific responses have also been described. These two scenarios may have different conservation implications. We tested these two hypotheses for Prionailurus cats (P. rubiginosus, P. bengalensis, P. viverrinus) in the Indian subcontinent and show its implications on species current protected area coverage and climatic suitability trends through time. We fitted ecological niche models with current environmental conditions and calculated niche overlap. In addition, we developed a model for the Jungle Cat Felis chaus to compare species responses and niche overlap estimates within Prionailurus with those for a related sympatric small cat species. Then we estimated the proportion of current suitable environment covered by protected area and projected climatic models from past (last interglacial) to future (2070; RCP4.5 and RCP8.5) conditions to show implications on population management and conservation. The hypothesis of a similar response and niche overlap among closely related species is not supported. Protected area coverage was lowest for P. viverrinus (mean = 0.071, SD = 0.012) and highest for P. bengalensis (mean = 0.088, SD = 0.006). In addition, the proportion of the subcontinent with suitable climate varied through time and was species-specific. For P. bengalensis, climatic suitability shrunk since at least the mid-Holocene, a trend that can be intensified by human-induced climate warming. Concerning P. viverrinus, most predictions show stable future climatic suitability, but a few indicated potential loss. Climatic suitability for P. rubiginous was predicted to remain stable but the species exhibited a negative association with intensive agriculture. Similar responses to environmental change by phylogenetically closely related species should not be assumed and have implications on protected area coverage and natural trends of species climatic suitability over time. This should be taken into account during conservation and management actions.


Attitudes toward defendants with substance-related charges: An analysis of a national sample of criminal defense attorneys.
While a large percentage of criminal offenders suffer from substance use disorders (SUDs), virtually nothing is known about the attitudes criminal defense attorneys possess toward their clients who are facing substance-related charges. This is a serious concern, as the burden of steering individuals with SUDs into treatment often falls to criminal defense attorneys. The goal of this study was to examine the attitudes of criminal defense attorneys toward individuals who have been accused of drug crimes. A questionnaire was sent to criminal defense attorneys (N = 1,933) from all 50 U.S. states and the District of Columbia. It was comprised of (i) demographic information and (ii) a version of the 11-item Medical Condition Regard Scale (MCRS). Criminal defense attorneys held generally positive attitudes toward clients with substance-related charges, but there was a significant divergence in attitudes between private and public attorneys, with the latter showing both greater familiarity with and better attitudes toward this same group of clients. These differences were impactful: worse attitudes toward clients strongly correlated with greater predictions that the clients would reoffend. Given the magnitude of the incarcerated population with SUDs and the centrality of defense attorneys in the treatment process, especially its initiation, the divergence in attitudes between private and public criminal defense attorneys is concerning. There is a clear need for increased collaboration between physicians and attorneys, with an aim of increasing the number of individuals with SUDs receiving proper treatment (Am J Addict 2018;XX:1-7).


Supporting Rape Survivors Through the Criminal Injuries Compensation Scheme: An Exploration of English and Welsh Independent Sexual Violence Advisors' Experiences.
English and Welsh responses to rape have long been critically examined, leading to attempted improvements in the criminal justice system. Despite this, little attention has been paid to the Criminal Injuries Compensation Scheme (CICS) and the difficulties applying it to rape. To begin addressing this gap, researchers interviewed three, and qualitatively surveyed 22, Independent Sexual Violence Advisors. The findings suggest that CICS may not only reinforce rape myths and disadvantage vulnerable survivors, but is also a source of validation and contributes to survivor justice. The study, while exploratory, therefore, highlights the need for further discussion about rape survivor compensation.


Small bowel perforation caused by pancreaticojejunal anastomotic stent migration after pancreaticoduodenectomy for periampullary carcinoma.
Pancreaticoduodenectomy is the gold standard for patients with resectable periampullary carcinoma. The protection of the anastomosis by positioning of an intraluminal stent is a technique used to lower the frequency of anastomotic fistulas. However the use of anastomotic stents is still debated and stent related complications are reported. A fifty-three-year old male underwent pancreaticoduodenectomy (PD) for a T2N0 periampullary carcinoma with a pancreaticojejunal (duct to mucosa) anastomosis protected by a free floating 6 Fr Nelaton stent in the Wirsung duct. Twenty-three months after surgery the patient accessed Emergency Department for severe abdominal pain associated to temperature, high white blood cell count and an significant increase in C reactive protein. Method Abdominal CT scan shown the presence of a tubular stent in the mesogastrium/lower right quadrant. No evident free intra-abdominal air was detected. The patient was submitted to explorative laparotomy. After debridement for localized peritonitis the Nelaton trans anastomotic stent was found in the abdomen. There was no evidence of bowel perforation, but intestinal loops covered with fibrin and suspect for impending perforation were resected. There is a lack of evidence about the true rate of post-operative complications related to pancreatic stenting. We believe that in patients presenting with abdominal pain or peritonitis that previously underwent PD with stent-guided pancreaticojejunal anastomosis, the hypothesis of stent migration should at least be taken into consideration.


Effects of cyanate on the distribution of isotope-labeled H2O and extracellular markers in rat liver and tumors.
Previous work has shown that administration of sodium cyanate inhibits the uptake of several metabolites in tumors under conditions in which there is generally no inhibition in normal tissues of the rat. In the present work, it was found that cyanate treatment inhibits the distribution of 3H2O, [3H]methoxyinulin, and [14C]sucrose in rats with greater effects in the tumors than the normal tissues examined. Tumor-bearing rats received i.p. injections of sodium cyanate (250 mg/kg body weight). After 60 min, the rats received s.c. injections of 3H2O. Treatment with cyanate decreased the radioactivity in blood and liver, but greater effects were seen in five transplanted tumors (LK1 colon tumor and Morris hepatomas 5123C, 7288CTC, 7777, and 9618A2). At 10 min after injection of 3H2O, the mean radioactivities in tumors of cyanate-treated rats were 11 to 23% of control values and in some tumors were still less than in controls at 60 min after isotope injection. Evidence was obtained that the action of cyanate was not due to osmotic effects or loss of water from the tissues. The distribution of the extracellular markers [3H]methoxyinulin and [14C]sucrose was also decreased in hepatomas in cyanate-treated rats. The data do not exclude effects on membrane permeability but suggested that cyanate decreased circulation in the tumors.


Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models.
To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicron and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.


Results of porous-coated anatomic total hip arthroplasty without cement at fifteen years: a concise follow-up of a previous report.
The purpose of this study was to update the results of a prospective series of primary cementless total hip arthroplasties after a minimum of fifteen years of follow-up. It is one of the first studies of cementless total hip arthroplasties followed for a minimum of fifteen years. One hundred consecutive Porous Coated Anatomic (PCA) total hip replacements were implanted between October 1983 and January 1986. Fifty-five patients (sixty-four hips) that were alive at a minimum of fifteen years postoperatively are the focus of the present study. At this time of follow-up, at an average of 15.6 years (range, fifteen to seventeen years) after the total hip arthroplasty, 17% (seventeen hips) of the entire cohort and 23% (fifteen hips) of the living cohort had undergone revision because of loosening of the acetabular component or osteolysis. Seven percent (seven hips) of the entire cohort and 6% (four hips) of the living cohort had undergone revision for loosening of the femoral component or osteolysis. Only four femoral stems had been revised for isolated loosening (without osteolysis). The PCA femoral component proved to be durable at a minimum of fifteen years postoperatively, while the acetabular component was less durable.


A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity.
To investigate the role of the kinase Zap70 in T cells, we generated mice expressing a Zap70 mutant whose catalytic activity can be selectively blocked by a small-molecule inhibitor. We found that conventional naive, effector and memory T cells were dependent on the kinase activity of Zap70 for their activation, which demonstrated a nonredundant role for Zap70 in signals induced by the T cell antigen receptor (TCR). In contrast, the catalytic activity of Zap70 was not required for activation of the GTPase Rap1 and inside-out signals that promote integrin adhesion. This Zap70 kinase-independent pathway was sufficient for the suppressive activity of regulatory T cells (T(reg) cells), which was unperturbed by inhibition of the catalytic activity of Zap70. Our results indicate Zap70 is a likely therapeutic target.


The dorsiflexion-eversion test for diagnosis of tarsal tunnel syndrome.
The clinical diagnosis of tarsal tunnel syndrome lacks objectivity and consistency. We have devised a new diagnostic physical examination test in which the tibial nerve is compressed as it runs beneath the flexor retinaculum behind the medial malleolus. In this test, the ankle is passively maximally everted and dorsiflexed while all of the metatarsophalangeal joints are maximally dorsiflexed and held in this position for five to ten seconds. We performed this test on fifty normal volunteers (100 feet) and on thirty-seven patients (forty-four feet) treated operatively for tarsal tunnel syndrome between 1987 and 1997. We performed the maneuver both preoperatively and postoperatively and recorded any consequent changes in the signs and symptoms; during the operation we observed the altered anatomical relationships in the tarsal tunnel that were produced by the maneuver. The average duration of follow-up was three years and eleven months. Before the operation, the signs and symptoms of tarsal tunnel syndrome were intensified or induced by the maneuver in fifteen of the twenty feet of the patients who reported numbness, in fifteen of the seventeen feet of those who reported pain alone, and in six of the seven feet of those who had combined numbness and pain. Local tenderness was intensified in forty-two of forty-three feet, and it was induced in one foot in which it had been previously absent. A Tinel sign became more pronounced in forty-one feet, and the sign was induced in three feet in which it had been absent previously. During the operation, the tibial nerve was stretched and compressed beneath the laciniate ligament when the ankle was dorsiflexed, the heel was everted, and the toes were dorsiflexed. Preoperative signs and symptoms disappeared on an average of 2.9 months after the operation, and they could not be induced by repeating the test except in three patients, all of whom had tarsal tunnel syndrome subsequent to a fracture of the calcaneus. In the normal volunteers, no symptoms or signs could be induced by the test. This new physical examination test is effective in facilitating the diagnosis of tarsal tunnel syndrome.


Replication and polypeptide synthesis of Mill Door/79, an orbivirus isolated from ticks from a seabird colony in Scotland.
The replication and polypeptide synthesis of orbivirus isolate Mill Door/79, a member of the Kemerovo serogroup, were studied. In Vero cells cell-associated virus exceeded cell-free virus by about 2 log10 PFU/ml. Attempts to purify the virus resulted in the demonstration of five polypeptides. Thirteen virus-induced polypeptides and 10 segments of double-stranded RNA were identified in infected cells. Partial proteolysis demonstrated homology between some polypeptides.


Phylogenetic lineages in the Botryosphaeriales: a systematic and evolutionary framework.
The order Botryosphaeriales represents several ecologically diverse fungal families that are commonly isolated as endophytes or pathogens from various woody hosts. The taxonomy of members of this order has been strongly influenced by sequence-based phylogenetics, and the abandonment of dual nomenclature. In this study, the phylogenetic relationships of the genera known from culture are evaluated based on DNA sequence data for six loci (SSU, LSU, ITS, EF1, BT, mtSSU). The results make it possible to recognise a total of six families. Other than the Botryosphaeriaceae (17 genera), Phyllostictaceae (Phyllosticta) and Planistromellaceae (Kellermania), newly introduced families include Aplosporellaceae (Aplosporella and Bagnisiella), Melanopsaceae (Melanops), and Saccharataceae (Saccharata). Furthermore, the evolution of morphological characters in the Botryosphaeriaceae were investigated via analysis of phylogeny-trait association. None of the traits presented a significant phylogenetic signal, suggesting that conidial and ascospore pigmentation, septation and appendages evolved more than once in the family. Molecular clock dating on radiations within the Botryosphaeriales based on estimated mutation rates of the rDNA SSU locus, suggests that the order originated in the Cretaceous period around 103 (45-188) mya, with most of the diversification in the Tertiary period. This coincides with important periods of radiation and spread of the main group of plants that these fungi infect, namely woody Angiosperms. The resulting host-associations and distribution could have influenced the diversification of these fungi. New families - Aplosporellaceae Slippers, Boissin & Crous, Melanopsaceae Phillips, Slippers, Boissin & Crous, Saccharataceae Slippers, Boissin & Crous.


Simulating activations with cytoarchitecture.
Cytoarchitectonic delineation of areas in post-mortem human brains provides the precise location of these areas. It has been possible to study the size and location of areas between post-mortem brains with multi-subject cytoarchitectonic data. If the structure-function relationship is assumed to be a one-to-one mapping for the purposes of inter-subject variability, then functional areas in the cortex will also adhere to the structure, and therefore, the location and size of cytoarchitectonic areas in the brain. Thus, it is possible to use the cytoarchitectonic data as being representative of the size and location of functional activations. Under this assumption, we simulated activations in cytoarchitectonic areas from ten post-mortem brains in this study. We then treated these data as we would a normal PET experiment. The purpose of this study is to demonstrate a standard PET image analysis on a simulated ten-subject PET study using cytoarchitecture to localize the activations. By doing so, we simulate activations with real inter-subject variability with the size and location of each area. Significant activations were obtained for activations simulated in areas 3a and 3b. A voxel-wise conjunction between simulated data and experimental data was made to better determine the underlying areas activated by the experimental tasks. This study presents a novel technique for demonstrating the effect of standard image analysis on the location and size of simulated activations as determined by cytoarchitectonic data from multiple subjects. Furthermore, this technique has been applied to better determine the underlying areas activated in an experiment.


Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts.
To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index. Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index). Two large, prospective cohort studies in Denmark. We measured levels of uric acid and related covariables in 58,072 participants from the Copenhagen General Population Study and 10,602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively. Blood pressure and prospectively assessed ischaemic heart disease. Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%). By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions.


Upper airways abnormalities and tracheal problems in Morquio's disease.
Morquio's disease is a metabolic disorder that can cause various respiratory abnormalities. Patients who live into adulthood are likely to develop upper airway problems and respiratory failure. With advances in home ventilation, these patients are increasingly likely to be referred to specialist respiratory units. We describe our experiences with two such patients.


Effects of targeted replacement of the tomatinase gene on the interaction of Septoria lycopersici with tomato plants.
Many plants produce constitutive antifungal molecules belonging to the saponin family of secondary metabolites, which have been implicated in plant defense. Successful pathogens of these plants must presumably have some means of combating the chemical defenses of their hosts. In the oat root pathogen Gaeumannomyces graminis, the saponin-detoxifying enzyme avenacinase has been shown to be essential for pathogenicity. A number of other phytopathogenic fungi also produce saponin-degrading enzymes, although the significance of these for saponin resistance and pathogenicity has not yet been established. The tomato leaf spot pathogen Septoria lycopersici secretes the enzyme tomatinase, which degrades the tomato steroidal glycoalkaloid alpha-tomatine. Here we report the isolation and characterization of tomatinase-deficient mutants of S. lycopersici following targeted gene disruption. Tomatinase-minus mutants were more sensitive to alpha-tomatine than the wild-type strain. They could, however, still grow in the presence of 1 mM alpha-tomatine, suggesting that nondegradative mechanisms of tolerance are also important. There were no obvious effects of loss of tomatinase on macroscopic lesion formation on tomato leaves, but trypan blue staining of infected tissue during the early stages of infection revealed more dying mesophyll cells in leaves that had been inoculated with tomatinase-minus mutants. Expression of a defense-related basic beta-1,3 glucanase gene was also enhanced in these leaves. These differences in plant response may be associated with subtle differences in the growth of the wild-type and mutant strains during infection. Alternatively, tomatinase may be involved in suppression of plant defense mechanisms.


Whistled Turkish alters language asymmetries.
Whistled languages represent an experiment of nature to test the widely accepted view that language comprehension is to some extent governed by the left hemisphere in a rather input-invariant manner. Indeed, left-hemisphere superiority has been reported for atonal and tonal languages, click consonants, writing and sign languages. The right hemisphere is specialized to encode acoustic properties like spectral cues, pitch, and melodic lines and plays a role for prosodic communicative cues. Would left hemisphere language superiority change when subjects had to encode a language that is constituted by acoustic properties for which the right hemisphere is specialized? Whistled Turkish uses the full lexical and syntactic information of vocal Turkish, and transforms this into whistles to transport complex conversations with constrained whistled articulations over long distances. We tested the comprehension of vocally vs. whistled identical lexical information in native whistle-speaking people of mountainous Northeast Turkey. We discovered that whistled language comprehension relies on symmetric hemispheric contributions, associated with a decrease of left and a relative increase of right hemispheric encoding mechanisms. Our results demonstrate that a language that places high demands on right-hemisphere typical acoustical encoding creates a radical change in language asymmetries. Thus, language asymmetry patterns are in an important way shaped by the physical properties of the lexical input.


Signal detection on the battlefield: priming self-protection vs. revenge-mindedness differentially modulates the detection of enemies and allies.
Detecting signs that someone is a member of a hostile outgroup can depend on very subtle cues. How do ecology-relevant motivational states affect such detections? This research investigated the detection of briefly-presented enemy (versus friend) insignias after participants were primed to be self-protective or revenge-minded. Despite being told to ignore the objectively nondiagnostic cues of ethnicity (Arab vs. Western/European), gender, and facial expressions of the targets, both priming manipulations enhanced biases to see Arab males as enemies. They also reduced the ability to detect ingroup enemies, even when these faces displayed angry expressions. These motivations had very different effects on accuracy, however, with self-protection enhancing overall accuracy and revenge-mindedness reducing it. These methods demonstrate the importance of considering how signal detection tasks that occur in motivationally-charged environments depart from results obtained in conventionally motivationally-inert laboratory settings.


Hegemonic masculinity: combining theory and practice in gender interventions.
The concept of hegemonic masculinity has been used in gender studies since the early-1980s to explain men's power over women. Stressing the legitimating power of consent (rather than crude physical or political power to ensure submission), it has been used to explain men's health behaviours and the use of violence. Gender activists and others seeking to change men's relations with women have mobilised the concept of hegemonic masculinity in interventions, but the links between gender theory and activism have often not been explored. The translation of 'hegemonic masculinity' into interventions is little examined. We show how, in South Africa and Sweden, the concept has been used to inform theoretically-based gender interventions and to ensure that men are brought into broader social efforts to build gender equity. We discuss the practical translational challenges of using gender theory broadly, and hegemonic masculinity in particular, in a Swedish case study, of the intervention Machofabriken [The Macho Factory], and illustrate how the concept is brought to life in this activist work with men. The concept has considerable practical application in developing a sustainable praxis of theoretically grounded interventions that are more likely to have enduring effect, but evaluating broader societal change in hegemonic masculinity remains an enduring challenge.


Fragmentation mechanism of UV-excited peptides in the gas phase.
We present evidence that following near-UV excitation, protonated tyrosine- or phenylalanine-containing peptides undergo intersystem crossing to produce a triplet species. This pathway competes with direct dissociation from the excited electronic state and with dissociation from the electronic ground state subsequent to internal conversion. We employ UV-IR double-resonance photofragment spectroscopy to record conformer-specific vibrational spectra of cold peptides pre-excited to their S1 electronic state. The absorption of tunable IR light by these electronically excited peptides leads to a drastic increase in fragmentation, selectively enhancing the loss of neutral phenylalanine or tyrosine side-chain, which are not the lowest dissociation channels in the ground electronic state. The recorded IR spectra evolve upon increasing the time delay between the UV and IR pulses, reflecting the dynamics of the intersystem crossing on a timescale of ~80 ns and <10 ns for phenylalanine- and tyrosine-containing peptides, respectively. Once in the triplet state, phenylalanine-containing peptides may live for more than 100 ms, unless they absorb IR photons and undergo dissociation by the loss of an aromatic side-chain. We discuss the mechanism of this fragmentation channel and its possible implications for photofragment spectroscopy and peptide photostability.


Constraints and efficiency of cattle marketing in semiarid pastoral system in Kenya.
Livestock keeping is regarded as a store of wealth for pastoralists in Kenya, besides their social and cultural functions. The objective of this study was to prioritize constraints to cattle marketing in a semiarid pastoral area of Narok in Kenya and to analyze efficiency of cattle marketing in transit markets located in Garissa, Kajiado and Narok counties. Primary data collection from traders was done through participatory interviews and market surveys, while time series market price data were obtained from secondary sources. Five focus group interviews were organized with a total of 61 traders in markets from Narok County, while a total of 187 traders who purchased cattle from transit markets provided data on a number of cattle purchased, purpose of purchase, buying prices and mode of transport. Market performance was analyzed through trader's market share, gross margins, Gini coefficient and coefficient of correlation between time series price data. The marketing constraints which were ranked high included lack of market for meat, trekking of cattle to markets, lack of price information and occurrence of diseases. About 10 % of traders purchased over 50 % of cattle which were supplied in markets, revealing a high concentration index. Further, a gross marketing margin per cattle purchased was positive in all markets revealing profitability. Moderate correlation coefficients existed between time series market price data for cattle purchased from Ewaso Ngiro and Mulot markets (r = 0.5; p < 0.05), while those between Dagoretti and Garissa markets were weak (r = 0.2; p > 0.05). The integration of markets, occurrence of diseases and trekking of cattle to markets are factors which may increase a risk of infectious disease spread. These results call for support of disease surveillance activities within markets in pastoral areas so that farms and systems which are connected are protected from threats of infectious diseases.


Detection of HIV-1-infected cells from patients using nonisotopic in situ hybridization.
We have demonstrated that a sensitive, nonisotopic in situ hybridization (ISH) assay can be used to detect HIV-infected cells from seropositive, asymptomatic individuals. Our assay is based on the detection of a biotinated HIV DNA probe hybridized to human immunodeficiency virus (HIV)-infected peripheral blood lymphocytes (PBL) using streptavidin and alkaline phosphatase to identify positive cells. This assay is rapid in that it can be performed within a day and is sensitive enough to unambiguously identify a rare, single, positive cell. Patient samples derived from HIV-seropositive hemophiliacs and HIV-seropositive infants were analyzed before and after coculture with normal PBL. The same samples were investigated using a Dupont P24 antigen-capture kit. It was found that ISH always detected the same positive samples as antigen capture, often in shorter times of coculture. In situ hybridization detected over half of our HIV-infected hemophilia patient population as virus positive, whereas the antigen capture assay detected less than one fourth as virus positive. In situ hybridization detected positive cells directly, without coculture, in 12 out of 35 (34%) hemophiliacs and in three out of eight (37%) infants. The speed, sensitivity, and confidence of ISH and nonisotopic detection indicates that it will be useful as a tool for clinical research and diagnosis.


Optimizing screening for osteoporosis in patients with fragility hip fracture.
Osteoporosis, the underlying cause of most hip fractures, is underdiagnosed and undertreated. The 2008 Joint Commission report Improving and Measuring Osteoporosis Management showed only an average of 20% of patients with low-impact fracture are ever tested or treated for osteoporosis. We developed an integrated model utilizing hospitalists and orthopaedic surgeons to improve care of osteoporosis in patients with hip fracture. Does our integrated model combining hospitalists and orthopaedic surgeons improve the frequency of evaluation for osteoporosis, screening for secondary causes, and patients' education on osteoporosis? Our Hospitalist-Orthopaedic Surgeon Integrated Model of Care was implemented in September 2009. We compared the rate of evaluation and treatment of osteoporosis in 140 patients admitted with fragility hip fracture at our institution before (70 patients) and after (70 patients) implementation of the care plan. Evaluation of patients for osteoporosis was higher in the postimplementation group compared to the preimplementation group (89% versus 24%). Screening of patients for secondary causes of osteoporosis was also improved in the postimplementation group (89% versus 0%), as was the proportion of patients who received education for osteoporosis management (89% versus 0%). Our model of integrated care by hospitalists and orthopaedic surgeons resulted in improvement in the evaluation for osteoporosis, screening for secondary causes of osteoporosis, and education on osteoporosis management in patients with hip fracture at our institution. This may have important implications for treatment of these patients. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Chemical synthesis of oligodeoxyribonucleotides containing the Dewar valence isomer of the (6-4) photoproduct and their use in (6-4) photolyase studies.
The pyrimidine(6-4)pyrimidone photoproduct, a major UV lesion formed between adjacent pyrimidine bases, is transformed to its Dewar valence isomer upon exposure to UVA/UVB light. We have synthesized a phosphoramidite building block of the Dewar photoproduct formed at the thymidylyl(3'-5')thymidine site and incorporated it into oligodeoxyribonucleotides. The diastereoisomers of the partially protected dinucleoside monophosphate bearing the (6-4) photoproduct, which were caused by the chirality of the phosphorus atom, were separated by reversed-phase chromatography, and the (6-4) photoproduct was converted to the Dewar photoproduct by irradiation of each isomer with Pyrex-filtered light from a high-pressure mercury lamp. The Dewar photoproduct was stable under both acidic and alkaline conditions at room temperature. After characterization of the isomerized base moiety by NMR spectroscopy, a phosphoramidite building block was synthesized in three steps. Although the ordinary method could be used for the oligonucleotide synthesis, benzimidazolium triflate as an alternative activator yielded better results. The oligonucleotides were used for the analysis of the reaction and the binding of Xenopus (6-4) photolyase. Although the affinity of this enzyme for the Dewar photoproduct-containing duplex was reportedly similar to that for the (6-4) photoproduct-containing substrate, the results suggested a difference in the binding mode.


Do changes in weight status affect cognitive function in children and adolescents with obesity? A secondary analysis of a clinical trial.
It is unclear whether an association exists between obesity in children/adolescents and cognitive function, and whether the latter can be altered by body mass index (BMI) standard deviation score (SDS) reductions. We aimed to determine whether an association exists between BMI SDS and cognitive function in children/adolescents with obesity engaged in an obesity intervention. Second, we sought to determine if BMI SDS reduction at 12 months was associated with improved cognitive function. Secondary analysis of a clinical trial. Participants (n=69) were recruited from an obesity intervention. Eligible participants (recruited June 2013 to June 2015) were aged 6-16 years, with a BMI ≥98th centile or BMI >91st centile with weight-related comorbidities. Primary outcome measure was change in BMI SDS from baseline at 12 months. Dependent variables of cognitive functioning and school achievement were assessed at baseline and 12 months, using dependent variables of cognitive functioning (elements of Ravens Standard Progressive Matrices, Wide Range Achievement Test-fourth edition and Wechsler Intelligence Scale for Children-fourth edition). At baseline, BMI SDS was not associated with all aspects of cognitive function tested (n=69). Reductions in BMI SDS over time did not alter cognitive function overall. However, there was a greater reduction in comprehension standard scores in participants who increased their BMI SDS (adjusted estimated difference -6.1, 95% CI -11.6 to -0.6; p=0.03). There were no observed associations between BMI SDS and cognitive function in participants, apart from comprehension in the exploratory analyses, which may have been a random finding. Further studies need to include larger longitudinal cohorts incorporating a wider BMI range at entry to determine whether our findings persist. ANZCTR12611000862943; Pre-results.


The effect of killing and preservative solutions on estimates of maggot age in forensic cases.
Length of the oldest maggots recovered from a body often provide an accurate estimate of the time since death. The length of maggots of Protophormia terraenovae (Robineau-Desvoidy) of known age, at peak of feeding, was measured after 5 days immersion in one of 15 killing and preservative solutions, some of which are routinely used at autopsy and in forensic entomology; controls were killed in boiling water. There was shrinkage in all 15 solutions which translated into an underage error of 9.7 h in 70% ethanol, 11 h in San Veino and 16.8 h in formalin. Larvae of Calliphora vicina (Robineau-Desvoidy) underwent even greater shrinkage, which resulted in an underage error of 19.2 h in 70% ethanol, 26.4 h in formalin and 28.8 h in San Veino. Young third instar larvae underwent more shrinkage than older ones, with underage errors (in hours) as follows: P. terraenovae-70% ethanol 24 and San Veino, 24; C. vicina-70% ethanol, 7.2 and San Veino, 14.4. Maggots killed in boiling water and then placed in preservative solutions did not shrink. Length of the crop, which may be useful in age estimates of postfeeding larvae, was not altered significantly for forensic purposes in these solutions. The highly significant alterations in maggot length underscore a need for standardization in the treatment of maggots collected at the crime scene and at autopsy if their length is to be interpreted in a valid and consistent way. Recommendations are made for treatment of maggots wherever they are collected.


Human polymorphisms in nicotinic receptors: a functional analysis in iPS-derived dopaminergic neurons.
Tobacco smoking is a public health problem, with ∼5 million deaths per year, representing a heavy burden for many countries. No effective therapeutic strategies are currently available for nicotine addiction, and it is therefore crucial to understand the etiological and pathophysiological factors contributing to this addiction. The neuronal α5 nicotinic acetylcholine receptor (nAChR) subunit is critically involved in nicotine dependence. In particular, the human polymorphism α5D398N corresponds to the strongest correlation with nicotine dependence risk found to date in occidental populations, according to meta-analysis of genome-wide association studies. To understand the specific contribution of this subunit in the context of nicotine addiction, an efficient screening system for native human nAChRs is needed. We have differentiated human induced pluripotent stem (iPS) cells into midbrain dopaminergic (DA) neurons and obtained a comprehensive characterization of these neurons by quantitative RT-PCR. The functional properties of nAChRs expressed in these human DA neurons, with or without the polymorphism in the α5 subunit, were studied with the patch-clamp electrophysiological technique. Our results in human DA neurons carrying the polymorphism in the α5 subunit showed an increase in EC50, indicating that, in the presence of the polymorphism, more nicotine or acetylcholine chloride is necessary to obtain the same effect. This human cell culturing system can now be used in drug discovery approaches to screen for compounds that interact specifically with human native and polymorphic nAChRs.-Deflorio, C., Blanchard, S., Carisì, M. C., Bohl, D., Maskos, U. Human polymorphisms in nicotinic receptors: a functional analysis in iPS-derived dopaminergic neurons.