Miracle-dz/UniFAR-FTUs huggingface dataset:
Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no additional efficacy in rheumatoid arthritis: an analysis of individual patient-level data.

OBJECTIVE To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA). METHODS In the extension of the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) study into an open-label study, all patients received CZP 400 mg every other week in combination with methotrexate (MTX). Before the open-label phase of the study, patients had received CZP 200 mg or 400 mg every other week, or placebo every other week, as add-on therapy to MTX. The open-label study included those who had completed the RAPID 1 study (to week 52) and also those who had been withdrawn from the study (at week 16, due to inadequate response). At 12 weeks and 48 weeks after enrollment in the open-label study, changes in the Disease Activity Score in 28 joints (DAS28) were compared in dose-escalation patients (200 mg increased to 400 mg every other week) versus stable-dosage patients (400 mg every other week), using cumulative probability plots of individual patient-level data. RESULTS In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early. CONCLUSION Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.
Primary blast lung injury prevalence and fatal injuries from explosions: Insights from postmortem computed tomographic analysis of 121 improvised explosive device fatalities

BACKGROUND Primary blast lung injury (PBLI) is an acknowledged cause of death in explosive blast casualties. In contrast to vehicle occupants following an in-vehicle explosion, the injury profile, including PBLI incidence, for mounted personnel following an external explosion has yet to be as well defined. METHODS This retrospective study identified 146 cases of UK military personnel killed by improvised explosive devices (IEDs) between November 2007 and July 2010. With the permission of Her Majesty’s Coroners, relevant postmortem computed tomography imaging was analyzed. PBLI was diagnosed by postmortem computed tomography. Injury, demographic, and relevant incident data were collected via the UK Joint Theatre Trauma Registry. RESULTS Autopsy results were not available for 1 of 146 cases. Of the remaining 145 IED fatalities, 24 had catastrophic injuries (disruptions), making further study impossible, leaving 121 cases; 79 were dismounted (DM), and 42 were mounted (M). PBLI was noted in 58 cases, 33 (79%) of 42 M fatalities and 25 (32%) of 79 DM fatalities (p < 0.0001). Rates of associated thoracic trauma were also significantly greater in the M group (p < 0.006 for all). Fatal head (53% vs. 23%) and thoracic trauma (23% vs. 8%) were both more common in the M group, while fatal lower extremity trauma (7% vs. 48%) was more commonly seen in DM casualties (p < 0.0001 for all). CONCLUSION Following IED strikes, mounted fatalities are primarily caused by head and chest injuries. Lower extremity trauma is the leading cause of death in dismounted fatalities. Mounted fatalities have a high incidence of PBLI, suggesting significant exposure to primary blast. This has not been reported previously. Further work is required to determine the incidence and clinical significance of this severe lung injury in explosive blast survivors. In addition, specific characteristics of the vehicles should be considered. LEVEL OF EVIDENCE Epidemiologic study, level IV.
Dynamic strength training in patients with early rheumatoid arthritis increases muscle strength but not bone mineral density.

OBJECTIVE To assess the effects of 12 months' dynamic strength training on muscle strength and bone mineral density (BMD) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis (RA). METHODS Thirty-two subjects in the training group (EG) and 33 in the control group (CG) completed the study. EG carried out strength training 2 times a week with moderate loads of 50-70% of repetition maximum. They were also encouraged to do recreational physical activities. CG performed recreational physical activities and range of motion exercises. Maximal strength of the knee extensors, trunk extensors and flexors, and grip strength were recorded with dynamometers. BMD was measured using dual x-ray absorptiometry. Modified Disease Activity Score, erythrocyte sedimentation rate, and pain were used for the estimation of disease activity, and Stanford Health Assessment Questionnaire to measure functional disability. RESULTS The 12 month resistance training in EG led to statistically significant mean increases of 22-35% in all muscle groups examined. CG patients were also able to increase their strength to some degree (3-24%), but at the end of the study strengths in CG were significantly lower than in EG. By the end of the study lumbar spine BMD had changed by +0.19% (4.24) in EG and by -1.14% (4.36) in CG. The corresponding changes of femoral BMD were +1.10% (3.71) and -0.03% (3.58). The changes in BMD were minor and statistically not significant in both groups. However, femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids (n = 15, 3 subjects from EG and 12 from CG) compared with changes in BMD among those not treated with systemic glucocorticoids (n = 50). CONCLUSION Minimally supervised strength training resulted in significant improvements in muscle strength without detrimental effects on disease activity. The detected annual changes in central BMD were minor and statistically insignificant in both groups. Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment.
A Critical Evaluation of Public Participation in the Sudanese Planning Mandates

In the last four decades, the concept of community participation is increasingly getting attention in most of the world. While there is quite extensive literature on the concept itself, the process of community participation evaluation still lags behind. The necessity to improve community participation requires understanding the context where plans are formulated, developed, approved and implemented. This context is guided by three main elements including; planning mandates and by laws; planners’ perception about community participation; and the actual planning practiced by planning institutions. Using Cohen and Uphoff three dimensions of participation as a benchmark, this article includes analysis of the extent to which planning mandates in Sudan provide guidance for planners in terms of what is participation and how and when to involve citizens in the planning process. This analysis was achieved through extensive literature reviews and critical study and analysis of planning mandates between 1950 and 2000. The conclusions drawn by this article show that planning mandates in Sudan have addressed the issue of Community Participation apprehensively in a very informative nature, the process of involving citizens in the planning process "as mandated" focus on area re-planning much more than urban/city planning. Equally, involving citizens as mandated occurs in the less important stages of planning.
CyberKnife Radiotherapy for Localized Prostate Cancer: Rationale and Technical Feasibility

There is a clear dose response for localized prostate cancer radiotherapy and there probably is a radiobiological rationale for hypo-fractionation. Combining the two should maximize tumor control and increase the therapeutic ratio. This study examines the rationale and technical feasibility of CyberKnife radiotherapy (a robotic arm-driven linear accelerator) for localized prostate cancer. Its ability to deliver non-coplanar non-isocentric arcs can yield maximally conformal isodoses. It is the only integrated system capable of target position verification and real-time tracking during delivery of conformal stereotactic radiotherapy. Inverse planning with the CyberKnife is used to design a course of radiotherapy for localized prostate cancer. Fiducial markers within the gland are used to verify organ position and track organ motion via an orthogonal pair of electronic x-ray imaging devices and provide real-time feedback correction to the robotic arm during delivery. Conformal isodose curves and dose volume histograms (DVH) are used to compare with an optimized Intensity-Modulated Radiotherapy (IMRT) plan actually delivered to the study patient based upon CT scan-derived organ volumes. The CyberKnife can produce superior DVHs for sparing of rectum and bladder and excellent DVHs for target coverage compared with IMRT, and possesses dose heterogeneities to the same degree as IMRT plans. Because of the significantly longer delivery times required it would be best suited for hypo-fractionated regimens. Such dose regimens might allow for biologically equivalent dose escalation without increased normal tissue toxicity. Since the CyberKnife can verify organ position and motion and correct for this in real-time it is the ideal means of achieving such excellent DVHs without a compromise in doses to normal tissues. These capabilities are essential if one contemplates hypo-fractionated regimens with large dose-per-fraction sizes (>5Gy to 10Gy) and dose-escalation.
Effect of extremely low frequency magnetic fields on cell proliferation and gene expression

Owing to concerns regarding possible effects of extremely low frequency magnetic fields (ELF‐MF) on human health, many studies have been conducted to elucidate whether ELF‐MF can induce modifications in biological processes. Despite this, controversies regarding effects of ELF‐MF are still rife. In this study, we investigated biological effects of ELF‐MF on MCF10A, MCF7, Jurkat, and NIH3T3 cell lines. ELF‐MF with a magnetic flux density of 1 mT at 60 Hz was employed to stimulate cells for 4 or 16 h, after which the effects of ELF‐MF on cell proliferation, cell death, cell viability, and DNA synthesis rates were assessed. Whereas Jurkat and NIH3T3 cells showed no consistent variation in cell number, cell viability, and DNA synthesis rate, MCF10A and MCF7 cells showed consistent and significant decreases in cell number, cell viability, and DNA synthesis rates. However, there was no effect of ELF‐MF on cell death in any of tested cell lines. Next, to investigate the effect of ELF‐MF on gene expression, we exposed MCF7 cells to 2 mT at 60 Hz for 16 h and examined transcriptional responses by using gene expression array. We found a gene, PMAIP1, that exhibited statistically significant variation using two‐fold cut‐off criteria and certified its expression change by using semi‐quantitative and quantitative reverse transcription polymerase chain reaction. From these results, we concluded that ELF‐MF could induce the delay of cell cycle progression in MCF7 and MCF10A cells in a cell context‐specific manner and could up‐regulate PMAIP1 in MCF7 cells. Bioelectromagnetics. 36:506–516, 2015. © 2015 Wiley Periodicals, Inc.
Design of a TS Based Fuzzy Nonlinear Unknown Input Observer with Fault Diagnosis Applications

An approach for nonlinear unknown input observer (NUIO) design for nonlinear systems representable by a Takagi-Sugeno (TS) fuzzy system. The proposed NUIO design for TS fuzzy systems is carried out for two cases: 1) the premise variables do not depend on the unmeasured state variables; and 2) the premise variables depend on the unmeasured state variables. Sufficient conditions for the existence of NUIOs are derived, and an LMI based observer design strategy is proposed. Once the NUIOs are designed, fault detection and isolation problems for nonlinear systems described by TS fuzzy systems using the new NUIO is presented. To solve the actuator fault isolation problem, a system structure with two groups of inputs where one group is treated as unknown inputs is developed. A bank of NUIOs is then designed in order to investigate the following fault diagnosis problems: 1) How can the NUIOs be used for detecting faults? 2) Under what conditions is it possible to isolate single and/or multiple faults? 3) What is the maximum number of faults that can be isolated simultaneously? 4) How can multiple fault isolation be achieved? The article presents an NUIO based fault detection scheme for problem 1, gives sufficient conditions for problem 2, determines the maximum number of faults that can be isolated for problem 3, and proposes a fault diagnosis scheme using a bank of NUIOs to solve problem 4.
Model‐based analysis and design of a microchannel reactor for tissue engineering

Recently developed perfusion micro‐bioreactors offer the promise of more physiologic in vitro systems for tissue engineering. Successful application of such bioreactors will require a method to characterize the bioreactor environment required to elicit desired cell function. We present a mathematical model to describe nutrient/growth factor transport and cell growth inside a microchannel bioreactor. Using the model, we first show that the nature of spatial gradients in nutrient concentration can be controlled by both design and operating conditions and are a strong function of cell uptake rates. Next, we extend our model to investigate the spatial distributions of cell‐secreted soluble autocrine/paracrine growth factors in the bioreactor. We show that the convective transport associated with the continuous cell culture and possible media recirculation can significantly alter the concentration distribution of the soluble signaling molecules as compared to static culture experiments and hence needs special attention when adapting static culture protocols for the bioreactor. Further, using an unsteady state model, we find that spatial gradients in nutrient/growth factor concentrations can bring about spatial variations in the cell density distribution inside the bioreactor, which can result in lowered working volume of the bioreactor. Finally, we show that the nutrient and spatial limitations can dramatically affect the composition of a co‐cultured cell population. Our results are significant for the development, design, and optimization of novel micro‐channel systems for tissue engineering. © 2006 Wiley Periodicals, Inc.
Improving the detection of mTBI via Complexity Analysis by adopting an appropriate symbolization technique . A Magnetoencephalography Resting – State Study

Diagnosis of mild Traumatic Brain Injury (mTBI) was difficult due to the variability of obvious brain lesions using magnetic resonance imaging (MRI) or computed tomography (CT) scans. A promising tool for exploring potential biomarkers for mTBI is magnetoencephalography which has the advantage of high spatial and temporal resolution. By adopting proper analytic tools from the field of symbolic dynamics like Lempel-Ziv complexity (LZC), we can objectively characterize neural network alterations compared to healthy control. LZC is an estimator of the complexity of the system by enumerating the different patterns of the sequence. LZC needs first to binarize the time series using mean amplitude as the threshold. This procedure oversimplifies the rich information of brain activity captured via MEG. For that reason, we adopted neural-gas (NG) algorithm which has already been used for multichannel common symbolization. NG can transform a time series into more than two symbols by learning brain dynamics with a small error. To compare LZC with the NG symbolization approach, we adopted a proper complexity estimator called complexity index (CI). The whole analysis was presented to magnetoencephalographic (MEG) recordings of 30 mild Traumatic Brain Injury (mTBI) patients and 50 normal controls in δ frequency band. We compared CI and LZC via a classification procedure with k-NN and Support Vector Machines. Our results demonstrated that mTBI patients could be separated from normal controls with more than 97% classification accuracy based on CI with highest values considering to right frontal areas. In addition, a reversal relation between complexity and transition rate was demonstrated for both groups. These findings indicate that symbolization complexity could have a significant predictive value in the development of reliable biomarkers to help with the early detection of mTBI. Keywords—component; complexity; MEG; mTBI; Symbolization; Lempel-Ziv; Symbolic Dynamics
Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients.

The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10(-5); n = 54, 34%), MRD positive (between <10(-4) and ≥10(-5); n = 20, 12%), and MRD positive (≥10(-4); n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10(-4) and ≥10(-5) vs ≥10(-4) (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials. gov as #NCT01237249.
Effect of Squat Depth and Barbell Load on Relative Muscular Effort in Squatting

Abstract Bryanton, MA, Kennedy, MD, Carey, JP, and Chiu, LZF. Effect of squat depth and barbell load on relative muscular effort in squatting. J Strength Cond Res 26(10): 2820–2828, 2012—Resistance training is used to develop muscular strength and hypertrophy. Large muscle forces, in relation to the muscle's maximum force–generating ability, are required to elicit these adaptations. Previous biomechanical analyses of multi-joint resistance exercises provide estimates of muscle force but not relative muscular effort (RME). The purpose of this investigation was to determine the RME during the squat exercise. Specifically, the effects of barbell load and squat depth on hip extensor, knee extensor, and ankle plantar flexor RME were examined. Ten strength-trained women performed squats (50–90% 1 repetition maximum) in a motion analysis laboratory to determine hip extensor, knee extensor, and ankle plantar flexor net joint moment (NJM). Maximum isometric strength in relation to joint angle for these muscle groups was also determined. Relative muscular effect was determined as the ratio of NJM to maximum voluntary torque matched for joint angle. Barbell load and squat depth had significant interaction effects on hip extensor, knee extensor, and ankle plantar flexor RME (p < 0.05). Knee extensor RME increased with greater squat depth but not barbell load, whereas the opposite was found for the ankle plantar flexors. Both greater squat depth and barbell load increased hip extensor RME. These data suggest that training for the knee extensors can be performed with low relative intensities but require a deep squat depth. Heavier barbell loads are required to train the hip extensors and ankle plantar flexors. In designing resistance training programs with multi-joint exercises, how external factors influence RME of different muscle groups should be considered to meet training objectives.
Health Care Expenditure Prediction With a Single Item, Self-Rated Health Measure

Background:Prediction models that identify populations at risk for high health expenditures can guide the management and allocation of financial resources. Objective:To compare the ability for identifying individuals at risk for high health expenditures between the single-item assessment of general self-rated health (GSRH), “In general, would you say your health is Excellent, Very Good, Good, Fair, or Poor? ,” and 3 more complex measures. Study Design:We used data from a prospective cohort, representative of the US civilian noninstitutionalized population, to compare the predictive ability of GSRH to: (1) the Short Form-12, (2) the Seattle Index of Comorbidity, and (3) the Diagnostic Cost-Related Groups/Hierarchal Condition Categories Relative-Risk Score. The outcomes were total, pharmacy, and office-based annualized expenditures in the top quintile, decile, and fifth percentile and any inpatient expenditures. Data Source:Medical Expenditure Panel Survey panels 8 (2003–2004, n = 7948) and 9 (2004–2005, n = 7921). Results:The GSRH model predicted the top quintile of expenditures, as well as the SF-12, Seattle Index of Comorbidity, though not as well as the Diagnostic Cost-Related Groups/Hierarchal Condition Categories Relative-Risk Score: total expenditures [area under the curve (AUC): 0.79, 0.80, 0.74, and 0.84, respectively], pharmacy expenditures (AUC: 0.83, 0.83, 0.76, and 0.87, respectively), and office-based expenditures (AUC: 0.73, 0.74, 0.68, and 0.78, respectively), as well as any hospital inpatient expenditures (AUC: 0.74, 0.76, 0.72, and 0.78, respectively). Results were similar for the decile and fifth percentile expenditure cut-points. Conclusions:A simple model of GSRH and age robustly stratifies populations and predicts future health expenditures generally as well as more complex models.