Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

Randomized controlled trials reflected clinical practice when comparing the course of low back pain symptoms in similar populations.

OBJECTIVE:This study compares participants in randomized controlled trials (RCTs) (the Minimal Invasive Treatment [MinT] trials) to participants in a related observational study with regard to their low back pain (LBP) symptom course. STUDY DESIGN AND SETTING:Eligible patients were diagnosed with chronic LBP originating from the facet joints (N = 615) or sacroiliac (SI) joints (N = 533) and were treated with radiofrequency denervation and an exercise program. Randomized patients were compared to patients in the related observational study who fulfilled all RCT eligibility criteria (observational group 1) and to patients who did not fulfill at least one of the RCT eligibility criteria (observational group 2). Outcomes were pain intensity, treatment success, and functional status over a 3-month period. Longitudinal mixed-model analyses and linear regression models were applied to analyze the differences in outcomes between the RCT and observational study groups. RESULTS:No differences in symptom course were found between patients in the RCTs and patients in observational group 1. Patients with facet joint pain in observational group 2 had overall less treatment success (odds ratios [OR], 0.67; 95% confidence interval [CI], 0.50-0.90), and less improvement in physical functioning (mean difference [MD], 5.82; 95% CI, 2.54-9.11) compared to the RCT patients. Patients with SI joint pain in observational group 2 had higher pain scores (MD, 0.40; 95% CI, 0.09-0.72), less treatment success (OR, 0.72; 95% CI, 0.54-0.96), and less improvement in physical functioning (MD, 7.16; 95% CI, 3.84-10.47) compared to the RCT patients. CONCLUSION:This supports the generalizability of results from the MinT RCTs as this study suggests that these RCTs reflect clinical practice when comparing similar populations. To what extent this holds true for all RCTs in LBP should be further explored

Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.

Stratified care integrated with eHealth versus usual primary care physiotherapy in patients with neck and/or shoulder complaints: protocol for a cluster randomized controlled trial.

BACKGROUND: Neck and shoulder complaints are common in primary care physiotherapy. These patients experience pain and disability, resulting in high societal costs due to, for example, healthcare use and work absence. Content and intensity of physiotherapy care can be matched to a patient's risk of persistent disabling pain. Mode of care delivery can be matched to the patient's suitability for blended care (integrating eHealth with physiotherapy sessions). It is hypothesized that combining these two approaches to stratified care (referred to from this point as Stratified Blended Approach) will improve the effectiveness and cost-effectiveness of physiotherapy for patients with neck and/or shoulder complaints compared to usual physiotherapy. METHODS: This paper presents the protocol of a multicenter, pragmatic, two-arm, parallel-group, cluster randomized controlled trial. A total of 92 physiotherapists will be recruited from Dutch primary care physiotherapy practices. Physiotherapy practices will be randomized to the Stratified Blended Approach arm or usual physiotherapy arm by a computer-generated random sequence table using SPSS (1:1 allocation). Number of physiotherapists (1 or > 1) will be used as a stratification variable. A total of 238 adults consulting with neck and/or shoulder complaints will be recruited to the trial by the physiotherapy practices. In the Stratified Blended Approach arm, physiotherapists will match I) the content and intensity of physiotherapy care to the patient's risk of persistent disabling pain, categorized as low, medium or high (using the Keele STarT MSK Tool) and II) the mode of care delivery to the patient's suitability and willingness to receive blended care. The control arm will receive physiotherapy as usual. Neither physiotherapists nor patients in the control arm will be informed about the Stratified Blended Approach arm. The primary outcome is region-specific pain and disability (combined score of Shoulder Pain and Disability Index & Neck Pain and Disability Scale) over 9 months. Effectiveness will be compared using linear mixed models. An economic evaluation will be performed from the societal and healthcare perspective. DISCUSSION: The trial will be the first to provide evidence on the effectiveness and cost-effectiveness of the Stratified Blended Approach compared with usual physiotherapy in patients with neck and/or shoulder complaints. TRIAL REGISTRATION: Netherlands Trial Register: NL8249 . Officially registered since 27 December 2019. Date of first enrollment: 30 September 2020. Study status: ongoing, data collection

Bridging the gap between the economic evaluation literature and daily practice in occupational health: a qualitative study among decision-makers in the healthcare sector

Background: Continued improvements in occupational health can only be ensured if decisions regarding the implementation and continuation of occupational health and safety interventions (OHS interventions) are based on the best available evidence. To ensure that this is the case, scientific evidence should meet the needs of decision-makers. As a first step in bridging the gap between the economic evaluation literature and daily practice in occupational health, this study aimed to provide insight into the occupational health decision-making process and information needs of decision-makers.Methods: An exploratory qualitative study was conducted with a purposeful sample of occupational health decision-makers in the Ontario healthcare sector. Eighteen in-depth interviews were conducted to explore the process by which occupational health decisions are made and the importance given to the financial implications of OHS interventions. Twenty-five structured telephone interviews were conducted to explore the sources of information used during the decision-making process, and decision-makers' knowledge on economic evaluation methods. In-depth interview data were analyzed according to the constant comparative method. For the structured telephone interviews, summary statistics were prepared.Results: The occupational health decision-making process generally consists of three stages: initiation stage, establishing the need for an intervention; pre-implementation stage, developing an intervention and its business case in order to receive senior management approval; and implementation and evaluation stage, implementing and evaluating an intervention. During this process, information on the financial implications of OHS interventions was found to be of great importance, especially the employer's costs and benefits. However, scientific evidence was rarely consulted, sound ex-post program evaluations were hardly ever performed, and there seemed to be a need to advance the economic evaluation skill set of decision-makers.Conclusions: Financial information is particularly important at the front end of implementation decisions, and can be a key deciding factor of whether to go forward with a new OHS intervention. In addition, it appears that current practice in occupational health in the healthcare sector is not solidly grounded in evidence-based decision-making and strategies should be developed to improve this. © 2013 van Dongen et al.; licensee BioMed Central Ltd

The learning effect of intraoperative video-enhanced surgical procedure training

BACKGROUND: The transition from basic skills training in a skills lab to procedure training in the operating theater using the traditional master-apprentice model (MAM) lacks uniformity and efficiency. When the supervising surgeon performs parts of a procedure, training opportunities are lost. To minimize this intervention by the supervisor and maximize the actual operating time for the trainee, we created a new training method called INtraoperative Video-Enhanced Surgical Training (INVEST). METHODS: Ten surgical residents were trained in laparoscopic cholecystectomy either by the MAM or with INVEST. Each trainee performed six cholecystectomies that were objectively evaluated on an Objective Structured Assessment of Technical Skills (OSATS) global rating scale. Absolute and relative improvements during the training curriculum were compared between the groups. A questionnaire evaluated the trainee's opinion on this new training method. RESULTS: Skill improvement on the OSATS global rating scale was significantly greater for the trainees in the INVEST curriculum compared to the MAM, with mean absolute improvement 32.6 versus 14.0 points and mean relative improvement 59.1 versus 34.6% (P = 0.02). CONCLUSION: INVEST significantly enhances technical and procedural skill development during the early learning curve for laparoscopic cholecystectomy. Trainees were positive about the content and the idea of the curriculum

Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

[EN]Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.This work has been partially supported by the following grants: FIS 02/1244-FEDER, DTS 15/00119-FEDER, RTICC RD06/0020/0035-FEDER and RTICC RD12/0036/0048-FEDER from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain; SA103/03 and SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain. The research activities of the EuroFlow Consortium were supported by the European Commission (grant STREP EU-FP6, LSHB-CT-2006–018708, entitled ‘Flow cytometry for fast and sensitive diagnosis and follow-up of hematological malignancies’)

Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, PPeer reviewe

ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study

Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD. Fourteen children (8–15 years) with ADHD defined according to the DSM-IV-TR criteria were randomly allocated to 30 sessions of EEG-neurofeedback (n = 8) or placebo feedback (n = 6). Safety measures (adverse events and sleep problems), ADHD symptoms and global improvement were monitored. With respect to feasibility, all children completed the study and attended all study visits and training sessions. No significant adverse effects or sleep problems were reported. Regarding the expectancy, 75% of children and their parent(s) in the active neurofeedback group and 50% of children and their parent(s) in the placebo feedback group thought they received placebo feedback training. Analyses revealed significant improvements of ADHD symptoms over time, but changes were similar for both groups. This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD. However, a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds. Additionally, implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training. Based on the results of this pilot study, changes are made in the design of the ongoing study