Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

Objective: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. Methods: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. Results: Despite the small numbers,significant findings were possible. ADCmedian increased (p 30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). Conclusion: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. Advances in knowledge: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Proposal for a unified nomenclature for target site mutations associated with resistance to fungicides

Evolved resistance to fungicides is a major problem limiting our ability to control agricultural, medical and veterinary pathogens and is frequently associated with substitutions in the amino acid sequence of the target protein. The convention for describing amino-acid substitutions is to cite the wild type amino acid, the codon number and the new amino acid, using the one letter amino acid code. It has frequently been observed that orthologous amino acid mutations have been selected in different species by fungicides from the same mode of action class, but the amino acids have different numbers. These differences in numbering arise from the different lengths of the proteins in each species. The purpose of the current paper is to propose a system for unifying the labelling of amino acids in fungicide target proteins. To do this we have produced alignments between fungicide target proteins of relevant species fitted to a well-studied “archetype” species. Orthologous amino acids in all species are then assigned numerical “labels” based on the position of the amino acid in the archetype protein

The role of parental achievement goals in predicting autonomy-supportive and controlling parenting

Although autonomy-supportive and controlling parenting are linked to numerous positive and negative child outcomes respectively, fewer studies have focused on their determinants. Drawing on achievement goal theory and self-determination theory, we propose that parental achievement goals (i.e., achievement goals that parents have for their children) can be mastery, performance-approach or performance-avoidance oriented and that types of goals predict mothers' tendency to adopt autonomy-supportive and controlling behaviors. A total of 67 mothers (aged 30-53 years) reported their goals for their adolescent (aged 13-16 years; 19.4 % girls), while their adolescent evaluated their mothers' behaviors. Hierarchical regression analyses showed that parental performance-approach goals predict more controlling parenting and prevent acknowledgement of feelings, one autonomy-supportive behavior. In addition, mothers who have mastery goals and who endorse performance-avoidance goals are less likely to use guilt-inducing criticisms. These findings were observed while controlling for the effect of maternal anxiety

Use of conventional and alternative treatment strategies for a case of low back pain in a F/A-18 aviator

BACKGROUND: Low back pain can diminish jet pilot concentration and function during flight and be severe enough to ground pilots or cause decreased flying time. The objective of this case report is to present an example of the integration of chiropractic care with conventional treatments for the management of low back pain in a F/A-18 aviator. CASE PRESENTATION: The patient had insidious severe low back pain without radiation or neurological deficit, resulting in 24 hours of hospitalization. Spinal degeneration was discovered upon imaging. Four months later, it still took up to 10 minutes for him to get out of bed and several minutes to exit the jet due to stiffness and pain. He had discontinued his regular Marine Corps fitness training due to pain avoidance. Pain severity ranged from 1.5–7.1 cm on a visual analog scale. His Roland Morris Disability Questionnaire score was 5 out of 24. The pilot's pain was managed with the coordinated efforts of the flight surgeon, physiatrist, physical therapist, and doctor of chiropractic. Following this regimen he had no pain and no functional disability; he was able to fly multiple training missions per week and exercise to Marine Corps standards. CONCLUSION: A course of care integrating flight medicine, chiropractic, physical therapy, and physiatry appeared to alleviate pain and restore function to this F/A-18 aviator with low back pain

What the ‘Moonwalk’ Illusion Reveals about the Perception of Relative Depth from Motion

When one visual object moves behind another, the object farther from the viewer is progressively occluded and/or disoccluded by the nearer object. For nearly half a century, this dynamic occlusion cue has beenthought to be sufficient by itself for determining the relative depth of the two objects. This view is consistent with the self-evident geometric fact that the surface undergoing dynamic occlusion is always farther from the viewer than the occluding surface. Here we use a contextual manipulation ofa previously known motion illusion, which we refer to as the‘Moonwalk’ illusion, to demonstrate that the visual system cannot determine relative depth from dynamic occlusion alone. Indeed, in the Moonwalk illusion, human observers perceive a relative depth contrary to the dynamic occlusion cue. However, the perception of the expected relative depth is restored by contextual manipulations unrelated to dynamic occlusion. On the other hand, we show that an Ideal Observer can determine using dynamic occlusion alone in the same Moonwalk stimuli, indicating that the dynamic occlusion cue is, in principle, sufficient for determining relative depth. Our results indicate that in order to correctly perceive relative depth from dynamic occlusion, the human brain, unlike the Ideal Observer, needs additionalsegmentation information that delineate the occluder from the occluded object. Thus, neural mechanisms of object segmentation must, in addition to motion mechanisms that extract information about relative depth, play a crucial role in the perception of relative depth from motion

Reproducibility of postural control measurement during unstable sitting in low back pain patients

<p>Abstract</p> <p>Background</p> <p>Postural control tests like standing and sitting stabilometry are widely used to evaluate neuromuscular control related to trunk balance in low back pain patients. Chronic low back pain patients have lesser postural control compared to healthy subjects. Few studies have assessed the reproducibility of the centre of pressure deviations and to our knowledge no studies have investigated the reproducibility of three-dimensional kinematics of postural control tests in a low back pain population. Therefore the aim of this study was to assess the test-retest reproducibility of a seated postural control test in low back pain patients.</p> <p>Methods</p> <p>Postural control in low back pain patients was registered by a three dimensional motion analysis system combined with a force plate. Sixteen chronic low back pain patients having complaints for at least six months, were included based on specific clinical criteria. Every subject performed 4 postural control tests. Every test was repeated 4 times and lasted 40 seconds. The force plate registered the deviations of the centre of pressure. A Vicon-612-datastation, equipped with 7 infra-red M1 camera's, was used to track 13 markers attached to the torso and pelvis in order to estimate their angular displacement in the 3 cardinal planes.</p> <p>Results</p> <p>All Intraclass Correlation Coefficients (ICC) calculated for the force plate variables did not exceed 0.73 (ranging between 0.11 and 0.73). As for the torso, ICC's of the mean flexion-extension and rotation angles ranged from 0.65 to 0.93 and of the mean lateral flexion angle from 0.50 to 0.67. For the pelvis the ICC of the mean flexion-extension angle varied between 0.66 and 0.83, the mean lateral flexion angle between 0.16 and 0.81 and the mean rotation angle between 0.40 and 0.62.</p> <p>Consecutive data suggest that the low test-retest reproducibility is probably due to a learning effect.</p> <p>Conclusion</p> <p>The test-retest reproducibility of these postural control tests in an unstable sitting position can globally be considered as rather moderate. In order to improve the test-retest reproducibility, a learning period may be advisable at the beginning of the test.</p

Post-Kala-azar Dermal Leishmaniasis in Nepal: A Retrospective Cohort Study (2000–2010)

Post-kala-azar dermal leishmaniasis (PKDL) is a skin disorder seen in patients treated for Leishmania donovani visceral leishmaniasis (VL), a neglected tropical disease that is fatal if left untreated. In the Indian subcontinent, PKDL is seen in 5–10% of all past VL cases and is also reported in some without history of VL. As persons with PKDL do not feel sick, the disease has only cosmetic significance for the individual and treatment is rarely sought. However, PKDL lesions harbour parasites and therefore could represent a source of transmission, through the bite of female sand flies. Our study shows that the occurrence of PKDL in patients with past treated VL is low in Nepal compared to neighboring countries. Treatment of the original VL episode with SSG (sodium stibogluconate), inadequate treatment and treatment on ambulatory basis were significantly associated with PKDL. Though SSG has since been replaced by other drugs, counseling and supervision of adherence to the prescribed VL treatment is of vital importance to reduce risk of treatment failure and relapse as well as later development of PKDL. Policy makers should include surveillance and case management of PKDL in the VL elimination program

Predictors of nurses’ and midwives’ intentions to provide maternal and child healthcare services to adolescents in South Africa

BACKGROUND: Adolescent mothers are at a much higher risk for maternal mortality compared to mothers aged 20 years and above. Newborns born to adolescent mothers are also more likely to have low birth weight, with the risk of long-term effects such as early onset of adult diabetes than newborns of older mothers. Few studies have investigated the determinants of adequate quality maternal and child healthcare services to pregnant adolescents. This study was conducted to gain an understanding of nurses’ and midwives’ intentions to provide maternal and child healthcare and family planning services to adolescents in South Africa. METHODS: A total of 190 nurses and midwives completed a cross-sectional survey. The survey included components on demographics, knowledge of maternal and child healthcare (MCH) and family planning (FP) services, attitude towards family planning services, subjective norms regarding maternal and child healthcare and family planning services, self-efficacy with maternal and child healthcare and family planning services, and intentions to provide maternal and child healthcare and family planning services to adolescents. Pearson’s correlation analysis was conducted to determine the association between knowledge, attitude, subjective norms, self-efficacy, and intention variables for FP and MCH services. A 2-step linear regression analysis was then conducted for both FP and MCH services to predict the intentions to provide FP and MCH services to adolescents. RESULTS: Self-efficacy to conduct MCH services (β = 0.55, p < 0.01) and years of experience as a nurse- midwife (β = 0.14, p < 0.05) were associated with stronger intentions to provide the services. Self-efficacy to provide FP services (β = 0.30, p < 0.01) was associated with stronger intentions to provide FP services. CONCLUSIONS: Self-efficacy has a strong and positive association with the intentions to provide both MCH and FP services, while there is a moderate association with attitude and norms. There is a need to improve and strengthen nurses’ and midwives’ self-efficacy in conducting both MCH and FP services in order to improve the quality and utilization of the services by adolescents in South Africa.IS

Cost-effectiveness of exercise therapy versus general practitioner care for osteoarthritis of the hip: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is the most common joint disease, causing pain and functional impairments. According to international guidelines, exercise therapy has a short-term effect in reducing pain/functional impairments in knee OA and is therefore also generally recommended for hip OA. Because of its high prevalence and clinical implications, OA is associated with considerable (healthcare) costs. However, studies evaluating cost-effectiveness of common exercise therapy in hip OA are lacking. Therefore, this randomised controlled trial is designed to investigate the cost-effectiveness of exercise therapy in conjunction with the general practitioner's (GP) care, compared to GP care alone, for patients with hip OA.</p> <p>Methods/Design</p> <p>Patients aged ≥ 45 years with OA of the hip, who consulted the GP during the past year for hip complaints and who comply with the American College of Rheumatology criteria, are included. Patients are randomly assigned to either exercise therapy in addition to GP care, or to GP care alone. Exercise therapy consists of (maximally) 12 treatment sessions with a physiotherapist, and home exercises. These are followed by three additional treatment sessions in the 5th, 7th and 9th month after the first treatment session. GP care consists of usual care for hip OA, such as general advice or prescribing pain medication. Primary outcomes are hip pain and hip-related activity limitations (measured with the Hip disability Osteoarthritis Outcome Score [HOOS]), direct costs, and productivity costs (measured with the PROductivity and DISease Questionnaire). These parameters are measured at baseline, at 6 weeks, and at 3, 6, 9 and 12 months follow-up. To detect a 25% clinical difference in the HOOS pain score, with a power of 80% and an alpha 5%, 210 patients are required. Data are analysed according to the intention-to-treat principle. Effectiveness is evaluated using linear regression models with repeated measurements. An incremental cost-effectiveness analysis and an incremental cost-utility analysis will also be performed.</p> <p>Discussion</p> <p>The results of this trial will provide insight into the cost-effectiveness of adding exercise therapy to GPs' care in the treatment of OA of the hip. This trial is registered in the Dutch trial registry <url>http://www.trialregister.nl</url>: trial number <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1462">NTR1462</a>.</p