LLukas22/scidocs huggingface dataset:
Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study.

UNLABELLED
Methylnaltrexone is effective for opioid-induced constipation (OIC) in advanced illness patients. This 4-week, double-blind, randomized, placebo-controlled study investigated the effect of subcutaneous methylnaltrexone on OIC in patients receiving opioids for chronic, nonmalignant pain. Patients (N = 460) received subcutaneous methylnaltrexone 12 mg once daily (QD) or every other day (alternating with placebo) compared with placebo. Assessments included bowel movement count, time of bowel movement, straining, sense of complete evacuation, Bristol Stool Form Scales, and quality of life. Within 4 hours of first dose, 34.2% of patients in both methylnaltrexone groups had rescue-free bowel movements (RFBMs) versus 9.9% on placebo (P < .001). The estimated number needed to treat was about 4. On average, 28.9% of methylnaltrexone QD and 30.2% of methylnaltrexone alternate-day dosing resulted in RFBMs within 4 hours versus 9.4% QD and 9.3% alternate-day placebo injections (both P < .001). Both methylnaltrexone groups had significantly shorter time to first RFBM (P < .001) and greater increase in number of weekly RFBMs (P < .05) versus placebo. Adverse events included abdominal pain, diarrhea, nausea, and hyperhidrosis. Bristol Stool Form Scale scores (P = .002) and sensation of complete evacuation (P < .04) were significantly superior with methylnaltrexone QD; both methylnaltrexone groups reported no or mild straining during RFBMs in the first 2 weeks (P < .02). At 4 weeks, a significantly greater improvement in patient-reported, constipation-specific quality of life was seen in the alternate-day dosing (P < .05) and QD (P < .001) groups.


PERSPECTIVE
We present data demonstrating that subcutaneous methylnaltrexone 12 mg given once daily (QD) or every other day provides significant relief of OIC and was generally well tolerated in patients with chronic, nonmalignant pain. These results expand on prior effectiveness observed for the treatment of OIC in advanced illness patients to a broader population.
Short-latency crossed spinal responses are impaired differently in sub-acute and chronic stroke patients

OBJECTIVE
Investigate if patients with supraspinal lesions have impaired interlimb spinal reflex pathways. The short-latency crossed spinal response will be investigated during sitting from the non-paretic to paretic and paretic to non-paretic extremities at different stimulation intensities in chronic and sub-acute stroke patients.


METHODS
The ipsilateral tibial nerve of the paretic and non-paretic extremities were stimulated at motor threshold, 35% M-max and 85% M-max of the ipsilateral soleus while the contralateral soleus was contracted from 5% to 15% of the maximum voluntary contraction of the paretic soleus.


RESULTS
Chronic patients (from both extremities) had significantly less prominent inhibitory responses than healthy controls (post hoc tests: P<.01-P<.05). The responses were significantly modulated by stimulus intensity in healthy controls and chronic patients (P<.001-P<.05) but not sub-acute patients (P>.05). Some sub-acute patients had significantly more variable responses than chronic patients and healthy controls (P<.001-P⩽.05).


CONCLUSIONS
Short-latency interlimb reflexes are impaired differently in sub-acute vs. chronic patients, are impaired from the non-paretic and paretic extremity, and abnormal when compared to healthy controls.


SIGNIFICANCE
The inappropriate coordination could result in an inability to quickly avoid obstacles following a mechanical disturbance to the ipsilateral extremity. It also indicates that bilateral descending projections affect the response.
Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group: children versus adolescents.

OBJECTIVE
The aim of this study was to report the frequency of common treatment-emergent adverse events (AEs) from selective serotonin reuptake inhibitors (SSRIs) in children, adolescents, and adults.


METHOD
AE data were obtained from all published double-blind, placebo-controlled SSRI studies of children and adolescents that separated AE findings by age group. The AE findings were pooled for purposes of age-group comparisons. Double-blind, placebo-controlled SSRI studies of adolescents (n = 2) and of adults identified in systematically identified trials (n = 22) were assessed to compare patterns and rates across the age span. Other reports, primarily from the published SSRI literature, were added to clarify the findings presented.


RESULTS
Activation and vomiting SSRI AEs were 2- to 3-fold more prevalent in children than in adolescents, and their rate was lowest in adults. Somnolence as a SSRI AE was uncommon in children; its rate increased with advancing age. Insomnia and nausea were common SSRI AEs across the age span. Activation AEs were a frequent reason for discontinuation from SSRI clinical trials in preadolescents, whereas somnolence, nausea, and insomnia AEs were the most common reasons for trial discontinuations in adults.


CONCLUSIONS
Children are particularly vulnerable to specific AEs from certain medications, such as SSRIs. It is likely that the level of children's biological immaturity explains part of this phenomenon.
Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma.

This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m(2) (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m(2), lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105.
A Digital Signature Scheme Secure Against Adaptive Chosen-Message Attacks

Shafi Goldwasser∗∗ Silvio Micali∗∗ Ronald L. Rivest ∗∗ Abstract We present a digital signature scheme based on the computational difficulty of integer factorization. The scheme possesses the novel property of being robust against an adaptive chosen-message attack: an adversary who receives signatures for messages of his choice (where each message may be chosen in a way that depends on the signatures of previously chosen messages) can not later forge the signature of even a single additional message. This may be somewhat surprising, since the properties of having forgery being equivalent to factoring and being invulnerable to an adaptive chosen-message attack were considered in the folklore to be contradictory. More generally, we show how to construct a signature scheme with such properties based on the existence of a “claw-free” pair of permutations – a potentially weaker assumption than the intractibility of integer factorization. The new scheme is potentially practical: signing and verifying signatures are reasonably fast, and signatures are compact.
Clinical benefit of joint distraction in the treatment of severe osteoarthritis of the ankle: proof of concept in an open prospective study and in a randomized controlled study.

OBJECTIVE
Osteoarthritis (OA) is a degenerative, disabling joint disease that affects >10% of the adult population. No effective disease-modifying treatment is available. In the present study, we used joint distraction, a relatively new treatment in which mechanical contact between the articular surfaces is avoided while intraarticular intermittent fluid pressure is maintained, to treat patients with severe OA of the ankle.


METHODS
Patients with severe ankle OA (n = 57) who were being considered for joint fusion (arthrodesis) were treated with joint distraction in an open prospective study. In addition, a randomized trial was performed in 17 patients to determine whether joint distraction had a better outcome than debridement. A standardized evaluation protocol (physical examination, assessment of pain, mobility, and functional ability) was used, and changes in radiographic joint space width and subchondral sclerosis were measured. Thirty-eight patients in the open study have been followed up for >1 year, with up to 5 years of followup in 7 of them (mean +/- SD followup 2.8 +/- 0.3 years). Patients in the randomized study have been followed up for 1 year.


RESULTS
Significant clinical benefit was found in three-fourths of the 57 patients in the open prospective study. Most interestingly, the improvement increased over time. Radiographic evaluation showed increased joint space width and decreased subchondral sclerosis. Moreover, joint distraction showed significantly better results than debridement.


CONCLUSION
The clinical benefit of joint distraction in the treatment of severe OA is proof of the concept. Although the followup remains relatively short and effects over time remain unpredictable, our study creates possibilities for the treatment of severe OA in general. Considering the high prevalence of OA and the lack of a cure for it, joint distraction as a treatment of severe OA may have great medical, social, and economic impact.
Impaired visual recognition of biological motion in schizophrenia

BACKGROUND
Motion perception deficits have been suggested to be an important feature of schizophrenia but the behavioral consequences of such deficits are unknown. Biological motion refers to the movements generated by living beings. The human visual system rapidly and effortlessly detects and extracts socially relevant information from biological motion. A deficit in biological motion perception may have significant consequences for detecting and interpreting social information.


METHODS
Schizophrenia patients and matched healthy controls were tested on two visual tasks: recognition of human activity portrayed in point-light animations (biological motion task) and a perceptual control task involving detection of a grouped figure against the background noise (global-form task). Both tasks required detection of a global form against background noise but only the biological motion task required the extraction of motion-related information.


RESULTS
Schizophrenia patients performed as well as the controls in the global-form task, but were significantly impaired on the biological motion task. In addition, deficits in biological motion perception correlated with impaired social functioning as measured by the Zigler social competence scale [Zigler, E., Levine, J. (1981). Premorbid competence in schizophrenia: what is being measured? Journal of Consulting and Clinical Psychology, 49, 96-105.].


CONCLUSION
The deficit in biological motion processing, which may be related to the previously documented deficit in global motion processing, could contribute to abnormal social functioning in schizophrenia.
Semi-active control of sliding isolated bridges using MR dampers : an experimental and numerical study

Sliding base-isolation systems used in bridges reduce pier drifts, but at the expense of increased bearing displacements under near-source pulse-type earthquakes. It is common practice to incorporate supplemental passive non-linear dampers into the isolation system to counter increased bearing displacements. Non-linear passive dampers can certainly reduce bearing displacements, but only with increased isolation level forces and pier drifts. The semi-active controllable non-linear dampers, which can vary damping in real time, can reduce bearing displacements without further increase in forces and pier drifts; and hence deserve investigation. In this study performance of such a ‘smart’ sliding isolation system, used in a 1:20 scaled bridge model, employing semi-active controllable magneto-rheological (MR) dampers is investigated, analytically and experimentally, under several near-fault earthquakes. A non-linear analytical model, which incorporates the non-linearities of sliding bearings and the MR damper, is developed. A Lyapunov control algorithm for control of the MR damper is developed and implemented in shake table tests. Analytical and shake table test results are compared. It is shown that the smart MR damper reduces bearing displacements further than the passive lowand high-damping cases, while maintaining isolation level forces less than the passive high-damping case. Copyright ? 2005 John Wiley & Sons, Ltd.
Neural networks vs . decision trees for intrusion detection

Signature based intrusion detection systems cannot detect new attacks. These systems are the most used and developed ones. Current anomaly based intrusion detection systems are also unable to detect all kinds of new attacks because they are designed to restricted applications on limited environment. Current hackers are using new attacks where neither preventive techniques mainly based on access control nor current intrusion detection systems can prevent the devastating results of these attacks against information systems. We enhance the notion of anomaly detection and we use both neural networks and decision trees for intrusion detection. Since these techniques are mainly applicable to misuse detection, we use our anomaly detection enhancement and improve these techniques for anomaly detection. Experimental results demonstrate that while neural networks are highly successful in detecting known attacks, decision trees are more interesting to detect new attacks. The proposed methods outperform previous work in detecting both known and new attacks.
Converting to doxercalciferol capsules from intravenous paricalcitol or doxercalciferol.

OBJECTIVE
The purpose of the 2 studies presented in this article was to determine the clinically appropriate dose of doxercalciferol capsules that is required to maintain similar intact parathyroid hormone control when converting from intravenous (IV) paricalcitol or doxercalciferol.


DESIGN
Both studies were multicenter, open-label, randomized designs comprising the following 3 periods: a screening period, a 5-week run-in period, and a 5-week treatment period.


SETTING
Dialysis centers in the United States.


PATIENTS
Patients with stage 5 chronic kidney disease receiving dialysis 3 times weekly for a minimum of 6 months and with recent intact parathyroid hormone measurements between 15.9 and 63.7 pmol/L (150 to 600 pg/mL) were included.


INTERVENTION
After a 5-week fixed-dose IV paricalcitol or doxercalciferol run-in period, subjects were randomized to doxercalciferol capsules for the 5-week treatment period. Conversion factors for the paricalcitol study were 0.5, 1.0, and 1.5 times the current paricalcitol dose. Conversion factors for the doxercalciferol study were 1.0, 1.5, and 2.0 times the current doxercalciferol injection dose.


RESULTS
The predicted conversion factor for paricalcitol injection to doxercalciferol capsules was 0.92, whereas the factor for doxercalciferol injection to doxercalciferol capsules was 1.49. No statistically significant changes in serum calcium and phosphorus levels were found in either study. The nature of adverse events was consistent with the administration of an active vitamin D therapy to patients with chronic kidney disease receiving dialysis.


CONCLUSION
The studies demonstrate patients on dialysis can be safely and effectively converted from IV paricalcitol or doxercalciferol to oral doxercalciferol.
A Discussion on IGBT Short-circuit Behavior and Fault Protection Schemes

AbstructIGBT’s are available with short-circuit withstand times approaching those of bipolar transistors. These IGBT’s can therefore be protected by the same relatively slow-acting circuitry. The more efficient IGBT’s, however, have lower shortcircuit withstand times. While protection of these types of IGBT’s is not difficult, it does require a reassessment of the traditional protection methods used for the bipolar transistors. An in-depth discussion on the behavior of IGBT’s under different short-circuit conditions is carried out and the effects of various parameters on permissible short-circuit time are analyzed. The paper also rethinks the problem of providing short-circuit protection in relation to the special characteristics of the most efficient IGBT’s. The pros and cons of some of the existing protection circuits are discussed and, based on the recommendations, a protection scheme is implemented to demonstrate that reliable short-circuit protection of these types of IGBT’s can be achieved without difficulty in a PWM motor-drive application. volts
Nodal symplectic spheres in ℂℙ2 with positive self-intersection

1: Let ω be the canonical Kähler structure on CP We prove that any ω-symplectic sphere with positive ordinary double points is isotopic, among such curves, to an algebraic curve. In other words, if J is a ω-tamed almost complex structure on CP, the rational J-curves with ordinary double points are isotopic to algebraic curves. Moreover, calling Nd the number of degree d rational J-curves going through 3d− 1 points “in general position”, it follows from the proof that Nd does not depend on the almost complex structure J . Since they were introduced by M. Gromov in 1985 [1], pseudo-holomorphic curves have proven to be powerful tools in global symplectic geometry. By comparing their spaces of curves, one can compare symplectic manifolds. The aim of this paper is to compare some pseudo-holomorphic and algebraic curves in CP. The result we propose here can nevertheless be formulated without the formalism of pseudo-holomorphic curves. Let ω denote the canonical Kähler form on CP. We have the following theorem: Theorem 1. Any symplectic sphere in (CP, ω) having only positive ordinary double point singularities is symplectically isotopic (among symplectic spheres with such singularities) to an algebraic curve. AMS classification: 53Cxx, 58Dxx, 58G03, 14H99
Inverse planning simulated annealing for magnetic resonance imaging-based intracavitary high-dose-rate brachytherapy for cervical cancer.

PURPOSE
To develop a technique using exclusively magnetic resonance imaging (MRI) to perform dwell position identification, targets and organs at risk delineation, and to apply inverse planning dose optimization to high-dose-rate brachytherapy for cervical cancer.


METHODS AND MATERIALS
We included 15 consecutive women treated with high-dose-rate (HDR) brachytherapy for cervical cancer. All patients underwent MRI after placement of tandem and ring applicator containing a gadodiamide-filled dummy marker. This technique allowed direct visualization of the source pathway and precise definition of the intra-applicator source positions. For each patient, we delineated gross target volume (GTV), high-risk clinical target volume (HR-CTV), and organs at risk on MRI, according to the European Gynecological GEC-ESTRO Working Group definitions. We performed inverse planning simulated annealing (IPSA) and analyzed the dose-volume histograms with the following endpoints: D(90), D(100), and V(100) for GTV and HR-CTV; D0.1 cc, D1 cc, D2 cc for bladder, rectum, and bowel; and dose at Point A.


RESULTS
The intra-applicator source pathway was easily visualized on MRI using the gadodiamide-filled marker. IPSA provided excellent target coverage. The mean D(90) and V(100) for HR-CTV were 103+/-5% and 92+/-3%, respectively. IPSA provided excellent bladder sparing. D1 cc and D2 cc of bladder were 73+/-10% and 67+/-10%, respectively.


CONCLUSIONS
We developed a novel technique that allows direct visualization of the intra-applicator source pathway on MRI. Using this technique, we successfully performed inverse planning directly from MRI.
Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand.

BACKGROUND
The life expectancy of patients undergoing a Fontan procedure is unknown.


METHODS AND RESULTS
Follow-up of all 1006 survivors of the 1089 patients who underwent a Fontan procedure in Australia and New Zealand was obtained from a binational population-based registry including all pediatric and adult cardiac centers. There were 203 atriopulmonary connections (AP; 1975-1995), 271 lateral tunnels (1988-2006), and 532 extracardiac conduits (1997-2010). The proportion with hypoplastic left heart syndrome increased from 1/173 (1%) before 1990 to 80/500 (16%) after 2000. Survival at 10 years was 89% (84%-93%) for AP and 97% (95% confidence interval [CI], 94%-99%) for lateral tunnels and extracardiac conduits. The longest survival estimate was 76% (95% CI, 67%-82%) at 25 years for AP. AP independently predicted worse survival compared with extracardiac conduits (hazard ratio, 6.2; P<0.001; 95% CI, 2.4-16.0). Freedom from failure (death, transplantation, takedown, conversion to extracardiac conduits, New York Heart Association III/IV, or protein-losing enteropathy/plastic bronchitis) 20 years after Fontan was 70% (95% CI, 63%-76%). Hypoplastic left heart syndrome was the primary predictor of Fontan failure (hazard ratio, 3.8; P<0.001; 95% CI, 2.0-7.1). Ten-year freedom from failure was 79% (95% CI, 61%-89%) for hypoplastic left heart syndrome versus 92% (95% CI, 87%-95%) for other morphologies.


CONCLUSIONS
The long-term survival of the Australia and New Zealand Fontan population is excellent. Patients with an AP Fontan experience survival of 76% at 25 years. Technical modifications have further improved survival. Patients with hypoplastic left heart syndrome are at higher risk of failure. Large, comprehensive registries such as this will further improve our understanding of late outcomes after the Fontan procedure.