Miracle-dz/UniFAR-FTUs huggingface dataset:
Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double-blind, controlled, add-on clinical trial.

OBJECTIVES Valproic acid's well-known teratogenicity limits its use in women of childbearing age. Valnoctamide is an analog of valproate that does not undergo biotransformation to the corresponding free acid. In mice, valnoctamide has been shown to be distinctly less teratogenic than valproate. Valnoctamide is an anticonvulsant, and we hypothesized that valnoctamide is antimanic. METHODS We performed a double-blind, five-week, add-on, controlled trial of valnoctamide in mania. Patients were treated with risperidone at doses of the physician's discretion. Valnoctamide or placebo was begun at doses of 600 mg/day and increased to 1200 mg after four days. Weekly ratings by a psychiatrist blind to the study drug were conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI). RESULTS Fifteen valnoctamide patients and 17 placebo patients completed at least one post-baseline week and were included in data analysis. In all efficacy measures valnoctamide was more effective than placebo as an add-on to risperidone, using two-way analysis of variance (ANOVA) with time as the within-subject factor. Two-way ANOVA showed a significant effect of time (p < 0.001) and significant interaction between treatment and time (YMRS: p = 0.012; BPRS: p = 0.007; CGI: p = 0.003). Differences between valnoctamide and placebo were significant from week 3 to week 5. CONCLUSION Valnoctamide could be an important valproate substitute for women of childbearing age with bipolar disorder who may become pregnant.
Central suboptimal H ∞ filter design for linear time-varying systems with state and measurement delays

This article presents the central finite-dimensional H ∞ filters for linear systems with state and measurement delay that are suboptimal for a given threshold γ with respect to a modified Bolza–Meyer quadratic criterion including the attenuation control term with the opposite sign. In contrast to the results previously obtained for linear time delay systems, this article reduces the original H ∞ filtering problem to H 2 (optimal mean-square) filtering problem using the technique proposed in Doyle, Glover, Khargonekar, and Francis (1989 ‘State-space Solutions to Standard H 2 and H ∞ Control Problems’, IEEE Transactions on Automatic Control, 34, 831–847). Application of the reduction technique becomes possible, since the optimal closed-form filtering equations solving the H 2 (mean-square) filtering problem have been obtained for linear systems with state and measurement delays. This article first presents the central suboptimal H ∞ filter for linear systems with state and measurement delays, based on the optimal H 2 filter from Basin, Alcorta-Garcia, and Rodriguez-Gonzalez (2005, ‘Optimal Filtering for Linear Systems with State and Observation Delays’, International Journal of Robust and Nonlinear Control, 15, 859–871), which consists, in the general case, of an infinite set of differential equations. Then, the finite-dimensional central suboptimal H ∞ filter is designed in case of linear systems with commensurable state and measurement delays, which contains a finite number of equations for any fixed filtering horizon; however, this number still grows unboundedly as time goes to infinity. To overcome that difficulty, the alternative central suboptimal H ∞ filter is designed for linear systems with state and measurement delays, which is based on the alternative optimal H 2 filter from Basin, Perez, and Martinez-Zuniga (2006, ‘Alternative Optimal Filter for Linear State Delay Systmes’, International Journal of Adaptive Control and Signal Processing, 20, 509–517). In all cases, the standard H ∞ filtering conditions of stabilisability, detectability and noise orthonormality are assumed. Finally, to relax the standard conditions, this article presents the generalised versions of the designed H ∞ filters in the absence of the noise orthonormality. The proposed H ∞ filtering algorithms provide direct methods to calculate the minimum achievable values of the threshold γ, based on the existence properties for a bounded solution of the gain matrix equation. Numerical simulations are conducted to verify the performance of the designed central suboptimal filters for linear systems with state and measurement delays against the central suboptimal H ∞ filter available for linear systems without delays. The simulation results show a definite advantage in the values of the noise-output transfer function H ∞ norms in favour of the designed filters.
A new networked predictive control approach for systems with random network delay in the forward channel

This article is concerned with the design of a networked predictive control (NPC) scheme with random network delay in the forward channel. A new design method of NPC is proposed. Correspondingly, the necessary and sufficient conditions on the stability of the closed-loop networked control system are derived. The merit of the proposed design method lies in its decreased conservativeness, which is achieved by packing the current predictive control signal with history predictive signals. By this means, the future plant input is known. Therefore, the state predictor can be designed such that its performance and stability will not be affected by the future input of the plant, while the existing design methods of NPC cannot do so. The proposed design method is shown to be much less conservative than the existing result through several examples.
The relationship of bipolar disorder lifetime duration and vascular burden to cognition in older adults.

OBJECTIVES We describe the cognitive function of older adults presenting with bipolar disorder (BD) and mania and examine whether longer lifetime duration of BD is associated with greater cognitive dysfunction. We also examine whether there are negative, synergistic effects between lifetime duration of BD and vascular disease burden on cognition. METHODS A total of 87 nondemented individuals with bipolar I disorder, age 60 years and older, experiencing manic, hypomanic, or mixed episodes, were assessed with the Dementia Rating Scale (DRS) and the Framingham Stroke Risk Profile (FSRP) as a measure of vascular disease burden. RESULTS Subjects had a mean (SD) age of 68.7 (7.1) years and 13.6 (3.1) years of education; 50.6% (n = 44) were females, 89.7% (n = 78) were white, and 10.3% (n = 9) were black. They presented with overall and domain-specific cognitive impairment in memory, visuospatial ability, and executive function compared to age-adjusted norms. Lifetime duration of BD was not related to DRS total score, any other subscale scores, or vascular disease burden. FSRP scores were related to the DRS memory subscale scores, but not total scores or any other domain scores. A negative interactive effect between lifetime duration of BD and FSRP was only observed with the DRS construction subscale. CONCLUSIONS In this study, lifetime duration of BD had no significant relationship with overall cognitive function in older nondemented adults. Greater vascular disease burden was associated with worse memory function. There was no synergistic relationship between lifetime duration of BD and vascular disease burden on overall cognition function. Addressing vascular disease, especially early in the course of BD, may mitigate cognitive impairment in older age.
Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM)

Bellivier F, Yon L, Luquiens A, Azorin J‐M, Bertsch J, Gerard S, Reed C, Lukasiewicz M. Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM). Bipolar Disord 2011: 13: 377–386. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.
Ephraim McDowell: The Qualities of a Good Surgeon

Objective:To identify those personal qualities which enabled Dr. Ephraim McDowell to be successful as the first surgeon in the world to remove a large ovarian tumor. Summary Background Data:Dr. McDowell, in 1809 and before anesthesia or antisepsis, removed a large ovarian tumor from his patient, Jane Todd Crawford, who then survived 33 years. Methods:Existing histories and accounts of Ephraim McDowell's life and operations were sifted for his personal qualities. A visit to the McDowell House and family 200th reunion in Danville, Kentucky, added details. Results:Qualities of confidence, compassion, courage, commitment, communication, courtesy, and especially cleanliness have been identified. Conclusions:Those qualities attributed to Ephraim McDowell perhaps were instrumental in his successes. Those basic qualities are still important for surgeons today.
Abatacept (CTLA-4IG) treatment reduces the migratory capacity of monocytes in patients with rheumatoid arthritis.

OBJECTIVE The binding of abatacept (CTLA-4Ig) to the B7 ligands CD80 and CD86 prevents the engagement of CD28 on T cells and thereby prevents effector T cell activation. In addition, a direct effect of CTLA-4Ig on antigen-presenting cells (APCs) could contribute to the therapeutic effect. To further elucidate the mechanism of CTLA-4Ig, we performed phenotype and functional analyses of APCs in patients with rheumatoid arthritis (RA) before and after the initiation of CTLA-4Ig therapy. METHODS Peripheral blood mononuclear cells were analyzed before and at 2 and 4 weeks after the initiation of CTLA-4Ig therapy. Proportions of APCs were determined by flow cytometry. CD14+ monocytes were further analyzed for the expression of costimulatory and adhesion molecules and for their transendothelial migratory capacity in vitro. In addition, CD14+ monocytes from healthy controls were analyzed for their migratory and spreading capacity. RESULTS Proportions and absolute numbers of monocytes were significantly increased in RA patients treated with CTLA-4Ig. The expression of several adhesion molecules was significantly diminished. In addition, monocytes displayed a significant reduction in their endothelial adhesion and transendothelial migratory capacity upon treatment with CTLA-4Ig. Likewise, isolated monocytes from healthy controls revealed a significant reduction in their migratory and spreading activity after preincubation with CTLA-4Ig or anti-CD80 and anti-CD86 antibodies. CONCLUSION We describe direct effects of CTLA-4Ig therapy on phenotype and functional characteristics of monocytes in RA patients that might interfere with the migration of monocytes to the synovial tissue. This additional mechanism of CTLA-4Ig might contribute to the beneficial effects of CTLA-4Ig treatment in RA patients.
Rotational thrombelastometry for the bedside monitoring of recombinant hirudin

Background: Recombinant hirudin is used as an alternative anticoagulant, particularly in patients with heparin‐induced thrombocytopenia type II. However, bedside monitoring for hirudin is not available. The present study aims to evaluate rotational thrombelastometry regarding its suitability to detect the effects of recombinant hirudin on whole blood coagulation. Hirudin was added to whole blood samples from healthy donors (n=5) and thrombelastometry variables resulting from activation of samples with tissue factor, ellagic acid, and ecarin were determined.
Topographic electroencephalogram in children during mask induction of anaesthesia with sevoflurane

Background: Epileptiform patterns, spikes, polyspikes and periodic epileptiform discharges (PED) have been reported in electroencephalograms (EEGs) during anaesthesia induction with sevoflurane in healthy adults and children. Published recordings have been performed with a limited number of channels, and therefore the topographic distributions of these patterns are not known.
Radioiodine Therapy: Review of the Empiric Fixed Dose Approaches and Their Selective Applications

Copyright c 2013, the Korean Thyroid Association. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 방사성요오드 치료: 경험적 고정용량투여방법에 대한 고찰과 선별적 응용
Early time course of altered leukocyte response to lipopolysaccharide and peptidoglycan in porcine gunshot injury

Background: Penetrating injuries are frequently combined with polybacterial soiling. Clearance of the microorganisms depends on the ability to activate immune responses, but post‐traumatic hyporeactivity of immune cells is almost universal. The aim of this study was to map the early time course of this altered leukocyte reactivity, and to compare the reactions to subsequent Gram‐positive or Gram‐negative challenges.
High body mass index is associated with increased diurnal strains in the articular cartilage of the knee.

OBJECTIVE Obesity is an important risk factor for osteoarthritis (OA) and is associated with changes in both the biomechanical and inflammatory environments within the joint. However, the relationship between obesity and cartilage deformation is not fully understood. The goal of this study was to determine the effects of body mass index (BMI) on the magnitude of diurnal cartilage strain in the knee. METHODS Three-dimensional maps of knee cartilage thickness were developed from 3T magnetic resonance images of the knees of asymptomatic age- and sex-matched subjects with normal BMI (18.5-24.9 kg/m2) or high BMI (25-31 kg/m2). Site-specific magnitudes of diurnal cartilage strain were determined using aligned images recorded at 8:00 AM and 4:00 PM on the same day. RESULTS Subjects with high BMI had significantly thicker cartilage on both the patella and femoral groove, as compared to subjects with normal BMI. Diurnal cartilage strains were dependent on location in the knee joint, as well as BMI. Subjects with high BMI, compared to those with normal BMI, exhibited significantly higher compressive strains in the tibial cartilage. Cartilage thickness on both femoral condyles decreased significantly from the AM to the PM time point; however, there was no significant effect of BMI on diurnal cartilage strain in the femur. CONCLUSION Increased BMI is associated with increased diurnal strains in articular cartilage of both the medial and lateral compartments of the knee. The increased cartilage strains observed in individuals with high BMI may, in part, explain the elevated risk of OA associated with obesity or may reflect alterations in the cartilage mechanical properties in subjects with high BMI.
Resource Utilization Associated With Procurement of Transplantable Organs From Donors That Do Not Meet OPTN Eligible Death Criteria

Background The strategy of evaluating every donation opportunity warrants an investigation into the financial feasibility of this practice. The purpose of this investigation is to measure resource utilization required for procurement of transplantable organs in an organ procurement organization (OPO). Methods Donors were stratified into those that met OPTN-defined eligible death criteria (ED donors, n=589) and those that did not (NED donors, n=703). Variable direct costs and time utilization by OPO staff for organ procurement were measured and amortized per organ transplanted using permutation methods and statistical bootstrapping/resampling approaches. Results More organs per donor were procured (3.66±1.2 vs. 2.34±0.8, P<0.0001) and transplanted (3.51±1.2 vs. 2.08±0.8, P<0.0001) in ED donors compared with NED donors. The variable direct costs were significantly lower in the NED donors ($29,879.4±11590.1 vs. $19,019.6±7599.60, P<0.0001). In contrast, the amortized variable direct costs per organ transplanted were significantly higher in the NED donors ($8,414.5±138.29 vs. $9,272.04±344.56, P<0.0001). The ED donors where thoracic organ procurement occurred were 67% more expensive than in abdominal-only organ procurement. The total time allocated per donor was significantly shorter in the NED donors (91.2±44.9 hr vs. 86.8±78.6 hr, P=0.01). In contrast, the amortized time per organ transplanted was significantly longer in the NED donors (23.1±0.8 hr vs. 36.9±3.2 hr, P<0.001). Discussion The variable direct costs and time allocated per organ transplanted is significantly higher in donors that do not meet the eligible death criteria.
Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometry

Background: Platelet dysfunction contributes to the pathophysiology of bleeding complications during and after cardiac surgery. In most surgical institutions, no peri‐operative point‐of‐care monitoring of platelet function is used. We evaluated the usefulness of the Multiplate® platelet function analyser based on impedance aggregometry for identifying groups of patients at a high risk of transfusion of platelet concentrates (PC).
Modified Fulkerson Osteotomy

ABSTRACT A method of performing the Fulkerson osteotomy is described, which creates an unusually stable fixation. The procedure involves the classic oblique osteotomy and intact distal bony bridge as well as a proximal dovetail roof and double bicortical screw fixation. This is followed by proximal soft tissue balancing. This modified technique allows a sufficiently strong construct that can (a) withstand the forces involved when the quadriceps is stimulated under anesthesia; (b) shorten the postoperative stay; and (c) minimize the time needed for postsurgical brace protection.
Changes in Mortality Patterns Following Total Hip or Knee Arthroplasty Over the Past Two Decades: A Nationwide Cohort Study

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective procedures for patients with moderate‐to‐severe osteoarthritis. Mortality rates after THA and TKA may have changed because of new surgical techniques, improvement of peri‐ and postoperative care, and performance of surgery in older patients having multiple comorbidities. However, data on secular mortality trends are scarce. We undertook this study to evaluate mortality patterns between 1989 and 2007 in patients undergoing elective THA and TKA.
Genetische und immunzytometrische Diagnostik bei der akuten myeloischen Leukämie und ihre Bedeutung für die Wahl der Therapiestrategie/Genetic and immunophenotypical diagnostics for acute myeloid leukemia and their implication on treatment strategy

Zusammenfassung Bei der akuten myeloischen Leukämie (AML) spielen zyto- und molekulargenetische Veränderungen eine zentrale Rolle in der Pathogenese, sind unverzichtbar für die diagnostische Kategorisierung, stellen die wichtigsten Faktoren für die Vorhersage des Therapieansprechens und der klinischen Prognose dar und werden zunehmend für spezifische Genotyp-adaptierte Induktions- und Konsolidierungsstrategien genutzt. Insbesondere für die AML-Entitäten Core-binding-factor AML, charakterisiert durch die t(8;21) und die inv(16)/t(16;16), und AML mit NPM1 Mutation sowie die AML mit einer FLT3 Internen Tandemduplikation zeichnen sich in klinischen Studien spezifische, molekular zielgerichtete Therapiestrategien ab. Der Zusammenhang zwischen der enormen Bedeutung der genetischen Veränderungen in der Leukämogenese und ihre Rolle als potentielle Zielstrukturen für bereits bekannte und neue Medikamente wird zur schrittweisen Substitution der rein Risiko-adaptierten zu einer immer mehr Genotyp-adaptierten Therapiestrategie führen. Abstract Cytogenetic and molecular genetic abnormalities in acute myeloid leukemia (AML) play an important role in the pathogenesis, are absolutely necessary for disease classification, are the most important prognostic factors for induction success and survival, and are increasingly used for specific genotype-adapted treatment approaches. In particular, molecular targeted treatment strategies are evolving within clinical trials in the AML entities core-binding factor AML, characterized by t(8;21) and inv(16)/t(16;16) and AML with mutated NPM1, as well as AML with an internal tandem duplication of the FLT3 gene. The link between the leukemogenic importance of genetic abnormalities and their role as a potential target for well-known and novel drugs will contribute to the stepwise replacement of purely risk-adapted therapy to a more and more genotype-adapted treatment strategy.
Mixed Cryoglobulinemia–Associated Vasculitis

The patient, a 75-year-old woman, presented with a 1-week history of dyspnea, cough, and fever. For the last 8 years, she had experienced recurrent episodes of purpura, arthralgias, and myalgias (Meltzer’s triad), which had been diagnosed as mixed cryoglobulinemia. Following admission, she developed respiratory and renal failure, hemodynamic instability, encephalopathy, palpable purpura, and digital necrosis (A) (arrow). Her rheumatoid factor level was 3,450 IU/ml, the C3 level was 0.20 gm/liter, the C4 level was 0.05 gm/liter, and the cryocrit reading was 33%. Viral serologic studies for human immunodeficiency virus, hepatitis B virus (HBV), HCV, and HCV RNA were negative. Bone marrow biopsy revealed normal frequencies of plasma cells without features suggestive of a lymphoproliferative disorder. Renal histopathologic evaluation showed glomeruli with amorphous, eosinophilic deposits in the capillary lumen, compatible with cryoglobulin deposits (B) (boxes). Electron microscopy confirmed the presence of subendothelial deposits in the glomerular capillary loops (C) (arrows). Widespread cryoglobulinemic vasculitis was diagnosed. A treatment regimen of plasmapheresis, corticosteroids, cyclophosphamide, and anti-CD20 monoclonal antibody (rituximab) was initiated, resulting in progressive reduction of the cryocrit reading (D) and complete clinical recovery. Most patients with mixed cryoglobulinemia have a chronic disease course limited to purpura, arthralgia, asthenia, and polyneuropathy (1). However, acute widespread cryoglobulinemic vasculitis occurs in 10–15% of cases. Patients with primary mixed cryoglobulinemia tend to have more severe disease than patients with secondary mixed cryoglobulinemia (2). Targeted B cell depletion with rituximab is an effective therapeutic option for life-threatening flares of cryoglobulinemic vasculitis that have not been responsive to treatment with glucocorticoids and/or immunosuppressive agents (3).
Multi-rate digital redesign of cascaded and dynamic output feedback systems

In this paper, a new indirect digital redesign method is presented for multi-rate sampled-data control systems with cascaded and dynamic output feedback controllers. These analogue controllers are often pre-designed based on desirable frequency specifications, such as bandwidth, natural angular frequency, etc. To take advantage of the digital controller over the analogue controller, digital implementation of these analogue controllers are often desirable. As only measured input-output signals are available, an ideal state reconstructing algorithm is utilised to obtain the multi-rate discrete-time states of the original continuous-time system. Based on the Chebyshev quadrature method, the gains of the multi-rate cascaded and the output feedback digital controllers are determined from their continuous-time counterparts according to the different sampling rates employed in the different parts of the closed-loop system. As a result, the respective analogue controllers with the high-frequency and low-frequency characteristics can be implemented using the respective fast-rate sampling and slow-rate sampling digital controllers. Unlike the classical direct bilinear transform method, which is an open-loop direct digital redesign method, the proposed digital controllers take into account the state-matching of the original continuous-time closed-loop system and the digitally redesigned sampled-data closed-loop system. To further improve the state-matching performance, an improved digital redesign approach is also developed to construct the multi-rate cascaded and dynamic output feedback digital controllers. Illustrative examples are given to demonstrate the effectiveness of the developed methods.