The effects of knee joint angle on neuromuscular activity during electrostimulation in healthy older adults

Introduction Electrostimulation devices stimulate the common peroneal nerve, producing a calf muscle-pump action to promote venous circulation. Whether knee joint angle influences calf neuromuscular activity remains unclear. Our aim was to determine the effects of knee joint angle on lower limb neuromuscular activity during electrostimulation. Methods Fifteen healthy, older adults underwent 60 min of electrostimulation, with the knee joint at three different angles (0°, 45° or 90° flexion; random order; 20 min each). Outcome variables included electromyography of the peroneus longus, tibialis anterior and gastrocnemius medialis and lateralis and discomfort. Results Knee angle did not influence tibialis anterior and peroneus longus neuromuscular activity during electrostimulation. Neuromuscular activity was greater in the gastrocnemius medialis (p = 0.002) and lateralis (p = 0.002) at 90°, than 0° knee angle. Electrostimulation intensity was positively related to neuromuscular activity for each muscle, with a knee angle effect for the gastrocnemius medialis (p = 0.05). Conclusion Results suggest that during electrostimulation, knee joint angle influenced gastrocnemii neuromuscular activity; increased gastrocnemius medialis activity across all intensities (at 90°), when compared to 0° and 45° flexion; and did not influence peroneus longus and tibialis anterior activity. Greater electrostimulation-evoked gastrocnemii activity has implications for producing a more forceful calf muscle-pump action, potentially further improving venous flow

Phase II study of intraperitoneal recombinant interleukin-12 (rhIL-12) in patients with peritoneal carcinomatosis (residual disease < 1 cm) associated with ovarian cancer or primary peritoneal carcinoma

<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic advantages of intraperitoneal (IP) rhIL-12, tumor response to IP delivery of other cytokines as well as its potential anti-angiogenic effect provided the rationale for further evaluation of IPrhIL-12 in patients with persistent ovarian or peritoneal carcinoma.</p> <p>Methods</p> <p>A phase 2 multi-institutional trial (NCI Study #2251) of IP rIL-12 (300 nanogram/Kg weekly) was conducted in patients with ovarian carcinoma or primary peritoneal carcinoma.</p> <p>Patients treated with primary therapy for ovarian cancer who had no extraabdominal/parenchymal disease or bulky peritoneal disease were eligible. Four to 8 weeks from last chemotherapy, eligible patients underwent a laparotomy/laparoscopy. Patients with residual disease ≤ 1 cm were registered for the treatment phase 2–5 weeks post surgery. The effect of IP rIL-12 on the expression of TNFα , INFα , IL-10, IP-10, IL-8, FGF, VEGF was also studied.</p> <p>Results</p> <p>Thirty-four patients were registered for the first screening phase of the study. Median age was 56.6 years (range: 31–71); 12 completed the second phase and were evaluable for response/toxicity. Performance scores of IL-12 treated patients were 0 (11 pts) and 1 (1 pt). There were no treatment related deaths, peritonitis or significant catheter related complications. Toxicities included grade 4 neutropenia (1), grade 3 fatigue (4), headache (2), myalgia (2), non-neutropenic fever (1), drug fever (1), back pain (1), and dizziness (1). The best response observed was SD. Two patients had SD and 9 had PD, and 1 was evaluable for toxicity only.</p> <p>Peritoneal fluid cytokine measurements demonstrated a ≥ 3 fold relative increase post-rhIL-12: IFN-γ, 5/5 pts; TNF-α , 1/5; IL-10, 4/5; IL-8, 5/5; and VEGF, 3/5. IP10 levels were increased in 5/5 patients. Cytokine response profiles suggest either NK or T-cell mediated effects of IP rhIL-12. Cytokine/chemokine results also suggest a pleiotropic response since proteins with potential for either anti-tumor (IFN-γ , IP-10) or pro-tumor growth effects (VEGF, IL-8) were detected.</p> <p>Conclusion</p> <p>IP IL-12 can safely be administered at this dose and schedule to patients after first line chemotherapy for ovarian/peritoneal carcinoma. The maximum response was stable disease. Future IP therapies with rhIL-12 will require better understanding and control of pleiotropic effects of IL-12.</p

Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene

Mutations in PROP1 are a common genetic cause of multiple pituitary hormone deficiency (MPHD). We used a comparative genomics approach to predict the transcriptional regulatory domains of Prop1 and tested them in cell culture and mice. A BAC transgene containing Prop1 completely rescues the Prop1 mutant phenotype, demonstrating that the regulatory elements necessary for proper PROP1 transcription are contained within the BAC. We generated DNA sequences from the PROP1 genes in lemur, pig, and five different primate species. Comparison of these with available human and mouse PROP1 sequences identified three putative regulatory sequences that are highly conserved. These are located in the PROP1 promoter proximal region, within the first intron of PROP1, and downstream of PROP1. Each of the conserved elements elicited orientation-specific enhancer activity in the context of the Drosophila alcohol dehydrogenase minimal promoter in both heterologous and pituitary-derived cells lines. The intronic element is sufficient to confer dorsal expansion of the pituitary expression domain of a transgene, suggesting that this element is important for the normal spatial expression of endogenous Prop1 during pituitary development. This study illustrates the usefulness of a comparative genomics approach in the identification of regulatory elements that may be the site of mutations responsible for some cases of MPHD

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Measurement of the inclusive and differential Higgs boson production cross sections in the decay mode to a pair of τ Leptons in pp collisions at sqrt[s]=13 TeV

Measurements of the inclusive and differential fiducial cross sections of the Higgs boson are presented, using the τ lepton decay channel. The differential cross sections are measured as functions of the Higgs boson transverse momentum, jet multiplicity, and transverse momentum of the leading jet in the event, if any. The analysis is performed using proton-proton collision data collected with the CMS detector at the LHC at a center-of-mass energy of 13  TeV and corresponding to an integrated luminosity of 138  fb^{-1}. These are the first differential measurements of the Higgs boson cross section in the final state of two τ leptons. In final states with a large jet multiplicity or with a Lorentz-boosted Higgs boson, these measurements constitute a significant improvement over measurements performed in other final states

Prevalence, antimicrobial susceptibility and risk factors associated with non-typhoidal Salmonella on Ugandan layer hen farms

Abstract Background Non-typhoidal Salmonella (NTS) are among the leading global foodborne pathogens and a significant public health threat. Their occurrence in animal reservoirs and their susceptibilities to commonly used antimicrobials are poorly understood in developing countries. The aim of this study was to estimate the prevalence, determine antimicrobial susceptibility and identify risk factors associated with NTS presence in laying hen farms in Uganda through a cross-sectional study. Results Pooled faecal samples were collected from 237 laying hen farms and these were analysed for NTS following standard laboratory procedures. In total, 49 farms (20.7%; 95% Confidence interval (CI): 15.6–25.6%) were positive for NTS presence. Altogether, ten Salmonella serotypes were identified among the confirmed 78 isolates, and the predominant serotypes were Salmonella Newport (30.8%), S. Hadar (14.1%), S. Aberdeen (12.8%), S. Heidelberg (12.8%), and S. Bolton (12.8%). Phenotypic antimicrobial resistance was detected in 45(57.7%) of the isolates and the highest resistance was against ciprofloxacin (50.0%) followed by sulphonamides (26.9%) and sulphamethoxazole/trimethoprim (7.7%). Resistance was significantly associated with sampled districts (p = 0.034). Resistance to three or more drugs, multi-drug resistance (MDR) was detected in 12 (15.4%) of the isolates, 9 (75%) of these were from Wakiso district. A multivariable logistic model identified large farm size (OR = 7.0; 95% CI: 2.5–19.8) and the presence of other animal species on the farm (OR = 5.9; 95% CI: 2.1–16.1) as risk factors for NTS prevalence on farms. Having a separate house for birds newly brought to the farms was found to be protective (OR = 0,4; 95% CI: 0.2–0.8). Conclusion This study has highlighted a high prevalence and diversity of NTS species in laying hen farms in Uganda and identified associated risk factors. In addition, it has demonstrated high levels of antimicrobial resistance in isolates of NTS. This could be because of overuse or misuse of antimicrobials in poultry production. Also importantly, the insights provided in this study justifies a strong case for strengthening One Health practices and this will contribute to the development of NTS control strategies at local, national and international levels

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

This paper reviews and extends searches for the direct pair production of the scalar supersymmetric partners of the top and bottom quarks in proton-proton collisions collected by the ATLAS collaboration during the LHC Run 1. Most of the analyses use 20 fb$^{-1}$ of collisions at a centre-of-mass energy of $\sqrt{s}$ = 8 TeV, although in some case an additional 4.7 fb$^{-1}$ of collision data at $\sqrt{s}$ = 7 TeV are used. New analyses are introduced to improve the sensitivity to specific regions of the model parameter space. Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models

Search for supersymmetry in final states with two or three soft leptons and missing transverse momentum in proton-proton collisions at root s=13 TeV

ArXiv ePrint: 2111.06296 (https://arxiv.org/abs/2111.06296).Copyright © 2022 CERN, for the benefit of the CMS Collaboration. A search for supersymmetry in events with two or three low-momentum leptons and missing transverse momentum is performed. The search uses proton-proton collisions at s√ = 13 TeV collected in the three-year period 2016–2018 by the CMS experiment at the LHC and corresponding to an integrated luminosity of up to 137 fb−1. The data are found to be in agreement with expectations from standard model processes. The results are interpreted in terms of electroweakino and top squark pair production with a small mass difference between the produced supersymmetric particles and the lightest neutralino. For the electroweakino interpretation, two simplified models are used, a wino-bino model and a higgsino model. Exclusion limits at 95% confidence level are set on χ∼02/χ∼±1 masses up to 275 GeV for a mass difference of 10 GeV in the wino-bino case, and up to 205(150) GeV for a mass difference of 7.5 (3) GeV in the higgsino case. The results for the higgsino are further interpreted using a phenomenological minimal supersymmetric standard model, excluding the higgsino mass parameter μ up to 180 GeV with the bino mass parameter M1 at 800 GeV. In the top squark interpretation, exclusion limits are set at top squark masses up to 540 GeV for four-body top squark decays and up to 480 GeV for chargino-mediated decays with a mass difference of 30 GeV.SCOAP3