Search

• ASMs with a very long half-life as co-medication do not affect LTM. • In the majority of cases there is no need for ASM withdrawal prior to LTM. • Baseline seizure frequency and FLE correlate with LTM seizure rates. • Seizure frequency and ASM reduction are associated with the first recorded seizure. • Enzyme inhibitor VPA is associated with longer time to first recorded seizure. To assess the impact of antiseizure medications (ASMs) with a very long half-life on long term video-EEG monitoring (LTM) in people with focal epilepsy (FE). In this retrospective cohort study, we searched our local database for people with FE who underwent ASM reduction during LTM at the University Hospital of 'La Fe', Valencia, from January 2013 to December 2019. Taking into account the half-life of the ASM, people with FE were divided into two groups: Group A contained individuals who were taking at least one ASM with a very long half-life at admission, and Group B consisted of those not taking very long half-life ASMs. Using multivariable analysis to control for important confounders, we compared the following outcomes between both groups: seizure rates per day, time to first seizure, and LTM duration. Three hundred seventy individuals were included in the study (154 in Group A and 216 in Group B). The median recorded seizure rates (1.3 seizures/day, range 0–15.3 vs.1.3 seizures/day, range 0–9.3, p-value=0.68), median time to the first seizure (24 h, range 2–119 vs. 24 h, range 2–100, p-value=0.92), and median LTM duration (4 days, range 2–5 vs. 4 days, range 2–5, p-value=0.94) were similar in both groups. Multivariable analysis did not reveal any significant differences in the three outcomes between the two groups (all p-values>0.05). ASMs with a very long half-life taken as co-medication do not significantly affect important LTM outcomes, including recorded seizure rates, time to the first seizure, or LTM duration. Therefore, in general, there is no need to discontinue ASMs with a very long half-life prior to LTM. [ABSTRACT FROM AUTHOR]

Disponibles depuis le début des années 1950, les glucocorticoïdes (GC) font aujourd'hui partie intégrante de la prise en charge de la polyarthrite rhumatoïde (PR). Leur rapidité d'action les rend particulièrement intéressants pour le traitement des poussées ou comme agents relais dans la PR débutante. L'efficacité des GC dans la PR a été établie, à la fois pour contrôler l'activité de la maladie et pour retarder la progression des dégradations articulaires. Parallèlement à ces bénéfices, les GC ont également des effets indésirables bien identifiés. Il est généralement déconseillé d'utiliser les GC sur de longues périodes, surtout à forte dose, et les directives récentes pour la prise en charge de la PR préconisent de ne pas recourir à ces agents, ou suggèrent de ne les utiliser qu'à titre de thérapie relais. Les perceptions relatives aux effets néfastes des GC, essentiellement fondées sur des études observationnelles, demeurent. Les corticothérapies prolongées à faible dose restent très prévalentes dans la pratique clinique, et des données récentes semblent indiquer que cette stratégie présente un rapport bénéfice–risque plutôt favorable, même chez les patients âgés. Ainsi, l'objectif de parvenir à équilibrer les bénéfices et les risques du traitement de la PR par des GC est toujours quelque peu controversé. Cette revue narrative met en avant la place, historique et actuelle, des GC dans la prise en charge de la PR, et résume les éléments récents étayant leurs effets bénéfiques et néfastes. De plus, des stratégies pratiques pour l'utilisation et la diminution des GC dans la PR sont proposées. Glucocorticoids have been available since the early 1950s and have since become an integral part of the management of rheumatoid arthritis (RA). Due to their rapid effect, glucocorticoids have an appealing profile for treating flares or as ''bridging'' agents in early RA. The efficacy of glucocorticoids to treat RA has been well established, both to control disease activity and to delay the progression of joint damage. However, despite their benefits, glucocorticoids have equally well-known adverse effects. It is generally accepted that long-term use of glucocorticoids, particularly at higher doses, is not advisable, and recent guidelines for the management of RA therefore either recommend against the use of glucocorticoids or suggest using them only as bridging therapy. Perceptions on the harmful effects of glucocorticoids remain, mainly based on observational studies. Prolonged glucocorticoid therapy at low doses is still highly prevalent in clinical practice, but recent data suggested a rather favourable risk-benefit balance for this strategy, even in senior patients. Balancing the benefits and risks of treating RA with glucocorticoids thus remains a somewhat controversial topic. Therefore, this narrative review outlines the historical and current position of glucocorticoids in the management of RA, while summarising recent evidence on their beneficial and detrimental effects. Furthermore, practical strategies for the current use and tapering of glucocorticoids in RA were formulated. [ABSTRACT FROM AUTHOR]

Les traitements de fond biologiques (bDMARD) occupent une place prépondérante dans la prise en charge de la spondylarthrite. Après l'obtention d'une rémission durable ou d'un faible niveau d'activité sous bDMARD, il est possible de maintenir cet état en réduisant la posologie de ces biothérapies. Les études démontrent de manière constante la non-infériorité de la décroissance des anti-TNF par rapport à la poursuite du traitement à pleine dose pour le maintien de la réponse thérapeutique mais les données disponibles sur la décroissance des inhibiteurs de l'interleukine-17 (anti-IL-17) sont rares. L'arrêt des anti-TNF et des anti-IL-17 expose toutefois les patients à un risque élevé de rechute et ne devrait pas être recommandé actuellement. Les bénéfices des schémas de décroissance et d'arrêt thérapeutique en matière de sécurité n'ont pas été clairement démontrés, les études n'étant généralement pas conçues pour évaluer cet aspect. Les données actuelles ne privilégient aucun protocole spécifique de décroissance ou d'arrêt mais le recours à un régime progressif ajusté sur l'activité de la maladie dans le cadre d'une approche plus personnalisée doit être encouragé. Des recherches supplémentaires seront nécessaires afin de clarifier ce qui constitue un « état acceptable de la maladie » pour entreprendre une décroissance ou un arrêt thérapeutique. Par ailleurs, aucun facteur prédictif fiable du succès de la décroissance ou de l'arrêt des traitements n'a encore été identifié. Une reprise évolutive du rhumatisme est possible après décroissance ou arrêt thérapeutique mais la réintroduction du bDMARD initial permet, dans la grande majorité des cas, de récupérer le contrôle de la maladie. Enfin, la plupart des patients se disent favorables à l'instauration de la décroissance lorsque préalablement informés des raisons et de l'intérêt de cette démarche. L'allégement et l'arrêt des traitements doivent faire l'objet d'une prise de décision partagée afin d'en améliorer les chances de succès. Biological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been achieved with bDMARDs, it may be possible to maintain this state with lower levels of these drugs. Studies consistently demonstrate that tapering of tumor necrosis factor alpha inhibitors (TNFi) is not inferior to full-dose continuation in terms of maintaining treatment response, while data for tapering of interleukin-17 inhibitors (IL-17i) is lacking. Complete discontinuation of TNFi and IL-17i, however, often results in relapse and should not be recommended at this moment. Clear safety benefits of tapering or discontinuation have not been shown, although studies were typically not designed to address this. Current evidence does not support specific tapering or discontinuation strategies, although stepwise disease activity-guided regimens do allow for a more personalized approach and might be preferred. The definition of what constitutes an appropriate disease state to initiate tapering or discontinuation is unclear, and requires further study. Also, reliable predictors of successful tapering and discontinuation have not yet been identified. Fortunately, if tapering or discontinuation fails, most patients are able to regain disease control when reverted to the original bDMARD regimen. Finally, most patients indicate that, when asked, they would be willing to try tapering if the rationale is clear and if it is in their best interests. The decision to taper or discontinue should be made through shared decision-making, as this could improve the likelihood of success. [ABSTRACT FROM AUTHOR]

Overprescription of pain medications directly fuels the opioid epidemic. Veterans are profoundly impacted. Tapered dose protocols may reduce excessive prescribing. A retrospective study of adult veterans who presented to our institution for primary total knee arthroplasty or total hip arthroplasty (THA) was performed. Postdischarge opioid use was reviewed before and after an opioid taper prescription protocol. The preprotocol and postprotocol groups had 299 and 89 veterans, respectively. Total Morphine Milligram Equivalent (MME) prescribed postdischarge, number of tablets prescribed, number of refills issued, 30-day emergency department visits, and 30-day readmissions were compared. Opioid naïve and chronic opioid users were both included. Preprotocol and postprotocol implementation group, in combination with surgery type (total knee arthroplasty versus THA) and opioid naïve status, predicted MME. On average, the postprotocol group received 224 MME less, THA patients received 177 MME less, and nonopioid naïve patients received 152 MME more. The opioid taper protocol led to less opioid administration after discharge. Taper protocols should be considered for postoperative pain management. III, retrospective comparison study. [ABSTRACT FROM AUTHOR]

In this paper, a novel fiber-optic axial-strain sensor based on a micro-cavity Fabry-Perot interferometer (FPI) is proposed and experimentally realized. This micro-cavity FPI is mainly composed of a micro-air-bubble in a tapered hollow-core fiber fabricated by arc-discharged multiple-tapering technique. The experimental results show that the maximum sensitivity of axial-strain can reach ∼8.9 p.m./με in the range from 0 to 1100 με with high linearity. Additionally, high repeatability and ultra-low crosstalk of temperature (∼0.078 με/°C) are demonstrated, which brings a detection accuracy of 1.5 %. With the merits of compactness, low cost and ease of fabrication, the proposed sensor is very promising and potential to high precision axial-strain related measurement. • An in-cavity micro-bubble based Fabry-Perot interferometer is fabricated by arc-discharged multiple-tapering technique. • A maximum sensitivity of ∼8.9 p.m./με is gained in the range from 0 to 1100 με, with high linearity and repeatability. • The sensor exhibits an ultra-low temperature cross-sensitivity of 0.078 με/°C, ensuring a detection accuracy of 1.5%. [ABSTRACT FROM AUTHOR]

• This work presents a comprehensive theoretical model that describes the mode coupling in strongly-coupled multicore fiber because of the tapering technique. • This study introduces a detailed theoretical model that characterizes mode coupling in strongly-coupled multicore fibers resulting from the tapering process. • The model incorporates an analysis of coupling between both adjacent and nonadjacent cores. • The coupling theory was assessed under two conditions: when light is injected into the central core and when it is injected into the external cores. We present a comprehensive theoretical model based on the coupled-mode theory, capable of analyzing the crosstalk in a multicore optical fiber taper. The novelty of our developed model lies in its ability to describe the mode coupling in strongly-coupled multicore fiber tapers, a feature not covered by previously reported models that are only suitable for weakly-coupled multicore fibers. In our approach, we consider all possible coupling interactions among both adjacent and nonadjacent cores, along with the self-coupling within each core of a homogeneous seven-core optical fiber. Moreover, we also take into account that when a homogeneous multicore fiber undergoes tapering, a propagation constant mismatch appears between the central and external cores, due to the closer proximity of the external cores to the surrounding environment. To validate our model, we implemented fiber tapers of different waist lengths and diameters in a seven-core optical fiber and compared their inter-core crosstalk with the simulated results. Unlike previous studies that only injected light into the central core, we also explored the case where the input is launched into any external core of the fiber tapers. For both scenarios, we verified that our theoretical model can describe the dynamics of mode coupling occurring in a tapered multicore fiber for a large range of waist diameters. We believe that the findings from this study could be useful for designing sensing and signal-processing devices. [ABSTRACT FROM AUTHOR]

Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA. [ABSTRACT FROM AUTHOR]

The semiparametric estimation of multivariate fractional processes based on the tapered periodogram of the differenced series is considered in this paper. We construct multivariate local Whittle estimators by incorporating the maximal efficient taper developed by Chen (2010). The proposed estimation method allows a wide range of potentially nonstationary long-range dependent series, being invariant to the presence of deterministic trends with the same extent of the differencing order, without a two-step procedure. We establish the consistency and asymptotic normality of the proposed estimators, which have no discontinuities, and show that the asymptotic variance is the same as that of the nontapered local Whittle estimation by increasing the order of a taper to infinity with a moderately slow rate. We examine the finite sample behavior of the proposed estimators through a simulation experiment. • A multivariate local Whittle estimation of fractional processes using the maximal efficient tapered periodogram is proposed. • The consistency and asymptotic normality of the proposed estimators are established. • We show that the efficiency loss in the estimators incurred by tapering is asymptotically recovered. [ABSTRACT FROM AUTHOR]

To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment. Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS≤2.4 and SJC≤1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics. A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ, and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare. A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients. [ABSTRACT FROM AUTHOR]

This paper describes the design and protocol of a pragmatic, randomized trial to evaluate the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Integrated Services for Pain: Interventions to Reduce Pain Effectively (INSPIRE) is a multicenter, randomized trial conducted at three academic health centers in the southeastern United States. Participants are adults receiving long-term opioid therapy of at least 20 morphine milligram equivalents daily for chronic noncancer pain. Participants were randomized to either the shared decision-making intervention or the motivational interviewing session and cognitive behavioral therapy for chronic pain intervention. All participants also received guideline-concordant care supporting opioid pharmacotherapy. The primary outcome was change from baseline in average daily prescribed opioid dose at 12 months, using prescribing data from electronic health records. Secondary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference and Physical Function at 12 months. This trial evaluates the comparative effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for chronic pain for the voluntary tapering of opioid dose in adults with chronic noncancer pain. Results from this study can guide clinicians, researchers, and policymakers as they seek to reduce opioid prescribing and improve management of chronic pain. ClinicalTrials.gov Identifier: NCT03454555 (https://clinicaltrials.gov/ct2/show/record/NCT03454555). Participant enrollment began on June 26, 2019. [ABSTRACT FROM AUTHOR]

• In patients with RA and SLE who have achieved a state of low disease activity or remission with low-dose glucocorticoids, tapering glucocorticoids increases the risk for flare. • There was no increased risk of adverse events with continued low-dose glucocorticoids, but the quality of evidence was very low and there are concerns about longer-term safety with low-dose glucocorticoids that were not addressed in this study. • Adrenal insufficiency was seen in only one of 238 patients who tapered low-dose glucocorticoids, and only in a trial that did not use a gradual glucocorticoid taper. To study the benefit and harm associated with continuing versus tapering low-dose glucocorticoids (GCs) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who have achieved low disease activity/remission. A protocolised (PROSPERO CRD42022325175) systematic review and meta-analysis of randomised trials was performed. Trials compared, in patients with low disease activity/remission and GCs at baseline, continued low-dose GCs (≤7.5 mg/d prednisone equivalent) with a taper. Co-primary outcomes were time to flare and adverse events (AEs), accompanied by secondary benefit and harm outcomes. We performed meta-analyses and evaluated risk of bias and quality of evidence (QoE). Subgroup analyses were conducted for patients with RA. Four trials (three: RA; one: SLE; study duration 24–104 weeks) with 472 participants were included. Tapering GCs resulted in a shorter time to flare (hazard ratio 3.41 [95 %-CI 1.96–5.93]; p <0.01; very low QoE). The risks of AEs, serious AEs, and withdrawal due to AEs were similar in both groups (very low to low QoE). There were more withdrawals due to lack of efficacy with tapered GCs (risk ratio 3.02 [1.56–5.87]; low QoE). In RA, the disease activity score-28 was lower with continued GCs (mean difference 0.49 [0.07–0.91]; low QoE). One of 238 patients in the tapering groups experienced adrenal insufficiency. Subgroup analyses yielded consistent results. In RA and SLE with low disease activity, continuing low-dose GCs may provide better sustained disease control, but QoE is insufficient. Adrenal insufficiency is very rare when tapering low-dose GCs. Longer-term safety concerns for GCs remain. [ABSTRACT FROM AUTHOR]

Purpose: To systematically evaluate the duration of focal onset seizures under medication withdrawal as a function of drug half-life.Methods: Adults with drug resistant focal epilepsy and invasive electroencephalographic (iEEG) recording between 01/2006 and 06/2016 (n = 128) were identified. Patients with multifocal or unknown epileptic foci were excluded, as well as subclinical seizures, isolated auras, or status epileptic. Antiepileptic drugs (AEDs) were withdrawn upon admission. The seizure duration was determined based on the invasive EEG data, and the latency since start of the monitoring was noted in hours. A negative binomial mixed model was used to compare the seizure durations before and after a cut-off, which was set at 2.5 half-lives of the individual anticonvulsive medication as this is thought to separate therapeutic and ineffective drug levels.Results: In total, 70 patients were included in the study and the duration of 672 seizures analyzed. On average, the patients were treated with 2.36 ± 0.78 AEDs. The individual cut-off of 2.5 half-lives was on average reached after 95.02 ± 80.18 h. The seizure frequency (321 vs. 351) and the rate of generalization (15.6% vs. 16.8%) was comparable before and after the individual cut-off point. The mean seizure duration was not statistically significantly prolonged after 2.5 half-lives by a factor of 1.168 for focal onset seizures (p = 0.090) and a factor of 1.091 for secondary generalized seizures (p = 0.545).Conclusions: Although AED withdrawal increases the likelihood for epileptic seizures, it did not prolong the seizure duration, nor did it increase the rate of secondary generalization in our study. [ABSTRACT FROM AUTHOR]

The following is a case report of an atypical presentation of spontaneous coronary artery disease. In this case, a male with risk factors, precipitated by an emotional stress, presented to the emergency room with atypical chest pain. Cardiac catheterization revealed tapering of the mid-left anterior descending artery, consistent with non-atherosclerotic spontaneous coronary artery disease. However due to repeat chest pain, a repeat cardiac catheterization was performed, revealing 100% occlusion of the mid-LAD. This case represents an atypical presentation of a pathology that is frequently missed, and underreported. This is important to discuss in order to increase awareness, as the management and follow up are actually conservative. [ABSTRACT FROM AUTHOR]

Background Oregon's Medicaid program is delivered through 16 Coordinated Care Organizations (CCOs) participating in a statewide performance improvement program to reduce high-dose opioid prescribing. CCOs were allowed flexibility to develop their own dose targets and any policies, trainings, guidelines, and/or materials to meet these targets. In this study, we characterize CCO strategies to reduce high-dose opioid prescribing across the 16 CCOs. Methods We reviewed relevant CCO documents and conducted semi-structured interviews with CCO administrators to acquire opioid-related policies, practices, timelines and contextual factors. We applied a systematic coding procedure to develop a comprehensive description of each CCO's strategy. We used administrative data from the state to summarize contextual utilization data for each CCO. Results Most CCOs selected a target daily morphine milligram equivalent (MME) dose of 90 mg. Sixteen issued quantity limits related to dose, eight restricted specific drug formulations (short-acting or long-acting), and 11 allowed for time-limited taper plan periods for patients over threshold. Many CCOs also employed provider trainings, feedback reports, and/or onsite technical assistance. Other innovations included incentive measures, electronic health record alerts, and toolkits with materials on local alternative therapy resources and strategies for patient communication. CCOs leveraging collaborations with regional partners appeared to mount a greater intensity of interventions than independently operating CCOs. Conclusions CCOs developed a diversity of interventions to confront high-risk opioid prescribing within their organization. As healthcare systems mount interventions to reduce risky opioid prescribing, it is critical to carefully describe these activities and examine their impact on process and health outcomes. [ABSTRACT FROM AUTHOR]

Objectives: An insomnia characterized by nighttime symptoms and daytime impairment is common. GABA-A receptor agonist (GABAA-RA) treatment is often used, but long-term use is controversial due to the poor risk-benefit ratio resulting from drug dependence and potential cognitive impairment. This study evaluated the effectiveness of add-on cognitive behavioral therapy for insomnia (CBT-I) and GABAA-RA dose-tapering in patients with primary insomnia resistant to pharmacotherapy.Methods: This randomized, multicenter, two-arm, parallel-group study compared CBT-I and treatment as usual (TAU) in patients with persistent primary insomnia despite GABAA-RA treatment. Screening was based on sleep diary entries, with ≥31-min sleep latency or wake after sleep onset, occurring ≥3 times in a week and total score of ≥8 on the Insomnia Severity Index (ISI). Primary outcome measures were severity of insomnia and GABAA-RA tapering rate.Results: A total of 51 patients were randomized and 49 patients were analyzed (CBT-I; n = 23, TAU; n = 26). A mixed-effects repeated-measures model revealed significant improvement in insomnia symptoms (ISI score) during the post-intervention (PI) and follow-up (FU) periods in the CBT-I versus the TAU group (PI; 10.91 vs. 14.33, p < 0.05, FU; 10.17 vs. 14.34, p < 0.01). GABAA-RA tapering rate approached 30% during follow-up in the CBT-I group; no significant intergroup difference was observed.Conclusion: Add-on CBT-I improved insomnia symptoms that were unresponsive to GABAA-RA therapy. No effect on tapering rate was observed in this study. CBT-I may promote dose reduction by optimizing the protocol and duration of treatment.Trial Registration: UMIN Clinical Trials Registry identifier: UMIN000014297. [ABSTRACT FROM AUTHOR]

Microchannel heat sinks (MCHS) are widely used for active cooling of electronics. Considerable enhancements in thermal performance are achievable by finning the MCHS to extend heat transfer area and create local flow turbulence. Yet, the literature lacks multi-objective geometric optimizations of the fin design. This study optimizes the geometry of tapered squared cross-section pin-fins in a square base MCHS, where the fins' dimensions are manipulated in terms of their area, clearance, tapering width, and tapering height ratios (AR, CR, TWR, and THR, respectively). The optimization is based on an experimentally validated computational model. The performance is analyzed for 256 finned MCHS configurations, compared with a reference unfinned MCHS. The results show a high dependency of thermal performance on AR and THR, where the hydraulic performance is more affected by AR. The executed genetic optimization procedure demonstrated non-dominated designs with thermal resistances ranging between 0.00078 and 0.0033 K/W and pressure losses ranging between 0.229 and 2.64 kPa. By considering these two performance metrics to be equally important, a balanced design with AR, CR, TWR, and THR of 0.284, 5.52 × 10−5, 0.6, and 1.0 was identified, which brings down the thermal resistance and pressure losses to only 0.000983 K/W and 0.7133 kPa, respectively. [Display omitted] • Key geometric parameters of pin fins in microchannel heat sinks are optimized. • Tapering height ratio has the largest impact on thermal performance. • Zero-clearance fins enhance the thermal performance but with large pressure drop. • Pareto designs have thermal resistances between 0.00078 and 0.0033 K/W. • The minimum thermal resistance is reduced by 35% via genetic optimization. [ABSTRACT FROM AUTHOR]

• Most of 708 users of antidepressants describe the prescriber of their drugs as uninformed about withdrawal symptoms. • Prescribers were also described as unable to provide effective support to withdraw from antidepressants. • Recommendations included individualised, gradual withdrawal plans, with small doses, liquids or tapering strips. • Psychotherapy, withdrawal support groups, patient-led services, nutrition advice and 24-hour crisis support also suggested. • Professional bodies should urgently disseminate evidence-based withdrawal information to GPs and Psychiatrists. Approximately half of the tens of millions of people currently taking antidepressants will experience withdrawal symptoms when they try to reduce or come off them. Nearly half of these describe their symptoms as severe in surveys. Many prescribing doctors seem ill-informed and unprepared to provide effective discontinuation advice and support, often misdiagnosing withdrawal as a relapse of depression or anxiety. 708 members of online support groups for people on antidepressants, from 31 countries, completed a sentence in an online survey: 'A public health service to help people come off antidepressants should include................'. Two independent researchers categorised their responses into themes, and then reached consensus via discussion. Seven themes emerged: 'Prescriber Role', 'Information', 'Other Supports/Services', 'Strong Negative Feelings re Doctors/Services etc.', Informed Consent When Prescribed', 'Drug Companies' and: 'Public Health Campaign'. The most frequently mentioned requirements of the Prescriber Role were that prescribers be properly informed, provide small doses/liquid/tapering strips, develop a withdrawal plan and believe patients about their withdrawal experiences. The most frequently recommended other services were psychotherapy/counselling, support groups, patient led/informed services, nutrition advice, 24-hour crisis support and 'holistic/lifestyle' approaches. Many respondents were angry about how uninformed their doctors were and how they had been treated. [ABSTRACT FROM AUTHOR]

A core-shell geometry is employed for most next-generation, three-dimensional opto-electric devices based on III–V semiconductors and grown by metal organic vapor phase epitaxy (MOVPE). Controlling the shape of the shell layers is fundamental for device optimization, however no detailed analysis of the influence of growth conditions has been published to date. We study homogeneous arrays of gallium nitride core-shell microrods with height and diameter in the micrometer range and grown in a two-step selective area MOVPE process. Changes in shell shape and homogeneity effected by deliberately altered shell growth conditions were accurately assessed by digital analysis of high-resolution scanning electron microscope images. Most notably, two temperature regimes could be established, which show a significantly different behavior with regard to material distribution. Above 900 °C of wafer carrier temperature, the shell thickness along the growth axis of the rods was very homogeneous, however variations between vicinal rods increase. In contrast, below 830 °C the shell thickness is higher close to the microrod tip than at the base of the rods, while the lateral homogeneity between neighboring microrods is very uniform. This temperature effect could be either amplified or attenuated by changing the remaining growth parameters such as reactor pressure, structure distance, gallium precursor, carrier gas composition and dopant materials. Possible reasons for these findings are discussed with respect to GaN decomposition as well as the surface and gas phase diffusion of growth species, leading to an improved control of the functional layers in next-generation 3D V–III devices. [ABSTRACT FROM AUTHOR]

Some patients presenting with dilated short bowel suffer from dysmotility, leading to stasis and consequent bacterial overgrowth. These patients are candidates for intestinal reconfiguration surgery. We suggest a technique of lengthening and tapering of the dilated short bowel segment named segmental intestinal reconfiguration (SIR) based on the modified Yang-Monti principle and submit the first clinical experience. The SIR technique was applied in a 10 years old patient with segmental bowel dilation of ultra-short bowel due to intestinal atresia and resection, who received parenteral nutrition 50% of the daily requirements. He was diagnosed with liver disease associated with intestinal failure, metabolic bone disorder, and polyarthritis. The dilated bowel loop was transected in three places to produce two segments 6 cm long. Antimesenteric borders of the segments were incised along, resulting in 2 rectangular flaps 12x6 cm. The flaps were closed into a tube diagonally to form two neosegments, sutured together and with the open intestinal ends. The length of the reconfigured bowel loop after SIR increased from 12 to 26 cm. The signs of dysmotility disappeared 3 weeks after the operation. In 18 months, the mid-term outcome was evaluated. There were no bacterial overgrowth or dysmotility episodes during this period. The child has become active, gaining weight and height. Parenteral nutrition was reduced in half. First clinical application of the SIR technique showed its simplicity, feasibility and positive effect on the motility. [ABSTRACT FROM AUTHOR]

The graded viscosity banks technology (tapering) for polymer flooding is studied for several different models of mixing zones behavior. Depending on the viscosity function the limiting polymer injection profile is rigorously derived for the transverse flow equilibrium model, for the Koval model and for the Todd–Longstaff model. The potential gain in the polymer quantity compared to the profile with a finite number of slugs is numerically estimated. [ABSTRACT FROM AUTHOR]

Glucocorticoids have been available since the early 1950s and have since become an integral part of the management of rheumatoid arthritis (RA). Due to their rapid effect, glucocorticoids have an appealing profile for treating flares or as "bridging" agents in early RA. The efficacy of glucocorticoids to treat RA has been well established, both to control disease activity and to delay the progression of joint damage. However, despite their benefits, glucocorticoids have equally well-known adverse effects. It is generally accepted that long-term use of glucocorticoids, particularly at higher doses, is not advisable, and recent guidelines for the management of RA therefore either recommend against the use of glucocorticoids or suggest using them only as bridging therapy. Perceptions on the harmful effects of glucocorticoids remain, although mainly based on observational studies. Prolonged glucocorticoid therapy at low doses is still highly prevalent in clinical practice, but recent data suggest a rather favourable risk-benefit balance for this strategy, even in senior patients. Balancing the benefits and risks of treating RA with glucocorticoids thus remains a somewhat controversial topic. This narrative review outlines the historical and current position of glucocorticoids in the management of RA, while summarising recent evidence on their beneficial and detrimental effects. Furthermore, practical strategies for the current use and tapering of glucocorticoids in RA are formulated. [ABSTRACT FROM AUTHOR]

Gas-injection enhanced oil recovery (EOR) has good displacement efficiency but poor sweep efficiency. Foam can improve sweep efficiency in these processes, but its direct injection would not be practical due to its poor injectivity. Field results suggest that the well injectivity can be improved if gas and surfactant solution are injected in alternating slugs, leading to foam creation inside porous medium as gas and surfactant intermingle in situ. This process, referred to as Surfactant Alternating Gas (SAG), aims at reducing gas mobility at the displacement front. Behind the front, because of low water saturation, foam collapses (partially or completely); thus, gas mobility gradually increases to its original mobility at the injection well. This can potentially lead to fingering of the highly-mobile gas into the region with low-mobility gas in the form of foam. To the best of our knowledge this phenomenon has not been investigated in the literature, apparently due to poor grid resolutions employed in the numerical simulations and/or focus on other parameters, from which it is difficult to infer instabilities. In this paper we use an implicit-texture foam model to simulate a SAG process with fine grid resolution. The magnitude of the instabilities decreases with weaker foam, coarser grid resolution, increasing diffusion, and inclusion of capillary pressure, suggesting that fingering reflects the intrinsic physics of the process: it is not a numerical artifact. In a successful SAG process, as long as there is enough surfactant ahead of the gas bank to form a region with low mobility, the fluid ahead of it is efficiently displaced (i.e., stable front exists). In numerical simulations, however, there are extremely low discrete mobility values in grid blocks located at the front. In such a process, there can be fingering within the foam bank (unstable displacement), while the foam front itself appears relatively stable. Further studies are required to verify the extent to which simulations of fingering reflect numerical artifacts at the front. These results have practical implications, especially in calculation of the well injectivity and design of optimum slug size and foam strength in a SAG process. [ABSTRACT FROM AUTHOR]

Resumo Justificativa e objetivos Uma boa prática clínica com o uso de opioides como parte de um regime abrangente de tratamento da dor pode enfrentar desafios significativos. Apesar das diretrizes provenientes de sociedades/organizações não governamentais para o manejo da dor, ainda existem obstáculos significativos. A revisão de alguns princípios básicos da analgesia com opioide com base na experiência e no conhecimento das publicações atuais sobre esse cuidado importante da saúde é justificável. Conteúdo De acordo com as diretrizes, a literatura apoia o uso da dose total mais baixa de opioides que forneça o controle adequado da dor com menos efeitos adversos. A titulação (teste), ao iniciar a administração de um opioide, é uma maneira de começar com uma concentração baixa e ir devagar (avaliar a adequação da fórmula específica de um opioide). O ajuste (individualização) é reconhecer que vários fatores contribuem para a experiência pessoal da dor de um indivíduo, tais como fatores físicos, psicológicos, sociais, culturais, espirituais, farmacogenômicos e comportamentais. Finalmente, para aqueles pacientes nos quais a transição (redução gradual) do opioide é desejada, fazer essa transição muito rapidamente pode ter consequências negativas e é possível minimizar os problemas durante essa etapa por meio de uma redução gradual. Conclusão Uma abordagem simultânea, agressiva, porém conservadora, é defendida na literatura em que a terapia com opioides é dividida em três etapas principais (os 3 Ts – em inglês: titration, tailoring, tapering ): titulação (teste), ajuste (individualização) e transição (redução gradual). Estabelecer os três Ts, juntamente com a aplicação de outra boa prática médica e experiência/julgamento clínico, incluindo abordagens não farmacológicas, pode ajudar os profissionais de saúde no esforço para alcançar o tratamento ideal da dor. Background and objectives Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. Content Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. Conclusion We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non‐pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain. [ABSTRACT FROM AUTHOR]

The prediction of natural frequencies of rectangular plates where a profiled indentation is present is made using a Rayleigh–Ritz variational energy method. Panels with holes are often found for access cables and access gaps, and it is shown that the application of damping to the profile leads to a more efficient method of reducing vibration than covering a whole rectangular plate, which is advantageous where weight saving is necessary. [ABSTRACT FROM AUTHOR]

Biological disease-modifying antirheumatic drugs (bDMARDs) have taken up an important role in the management of axial spondyloarthritis. Once stable remission or low disease activity has been achieved with bDMARDs, it may be possible to maintain this state with lower levels of these drugs. Studies consistently demonstrate that tapering of tumor necrosis factor alpha inhibitors (TNFi) is not inferior to full-dose continuation in terms of maintaining treatment response, while data for tapering of interleukin-17 inhibitors (IL-17i) is lacking. Complete discontinuation of TNFi and IL-17i, however, often results in relapse and should not be recommended at this moment. Clear safety benefits of tapering or discontinuation have not been shown, although studies were typically not designed to address this. Current evidence does not support specific tapering or discontinuation strategies, although stepwise disease activity-guided regimens do allow for a more personalized approach and might be preferred. The definition of what constitutes an appropriate disease state to initiate tapering or discontinuation is unclear, and requires further study. Also, reliable predictors of successful tapering and discontinuation have not yet been identified. Fortunately, if tapering or discontinuation fails, most patients are able to regain disease control when reverted to the original bDMARD regimen. Finally, most patients indicate that, when asked, they would be willing to try tapering if the rationale is clear and if it is in their best interests. The decision to taper or discontinue should be made through shared decision-making, as this could improve the likelihood of success. [ABSTRACT FROM AUTHOR]

• Tapering the anti-TNF α among ax-SpA patients in sustained remission was not related to disease flare. • Tapering biologics doses in a slowly manner is recommended. • Stopping biologics in ax-SpA in remission is not recommended. The emergence of biologics has improved the management of patients with rheumatic disease, mainly with spondyloarthritis (SpA). Sustained remission has become a reachable goal thanks to the treat to target strategy. Contrary to rheumatoid arthritis, data on biologic optimization among SpA patients in remission is scarce and still a subject of debate. The main objective of this systematic review was to provide the most up-to-date published literature regarding biologic tapering in axial spondyloarthritis. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until December 20th 2021, and tackling tapering strategies of the biologics in patients with axial SpA were included Fourteen studies met the inclusion criteria. They were published between 2008 and 2020. The most studied molecules were Etanercept (ETN) (n = 13), Infliximab (IFX) (n = 6), Adalimumab (ADA) (n = 5), certolizumab pegol (CZP) (n = 2), Golimumab (n = 1) and ETN biosimilar. There are no studies published regarding anti-IL 17 tapering strategy. Patient-tailored dose reduction of anti TNF-α agents was successful in preserving stable low disease activity in most of the studies with remission rates ranging between 20.2 % and 93.7 %. Complete treatment discontinuation is associated with a high risk of flares. To conclude, published data indicate that a progressive tapering strategy for anti TNF-α therapy is successful among axial SpA in sustained remission. However, further studies with more homogenized tapering strategies are needed in order to ascertain the specific implication of each subset for a better holistic approach. [ABSTRACT FROM AUTHOR]

This article reports the investigation of the growth behaviors of platinum-catalyzed GaN nanostructures grown via chemical vapor deposition method by manipulating growth temperature and ammonia flow rate. Morphological observation revealed the tapering behavior of GaN nanostructures at high growth temperatures and high ammonia flow rates in which the GaN nanowires were observed to be grown from the surface of GaN microcrystal structures. Growth mechanism of the tapering effect was discussed. X-ray diffraction showed the synthesized GaN nanostructures are of wurzite structure with no existence of impurities and found that GaN nanostructures grown at 1050 °C under ammonia flow rate of 250 sccm possessed the highest degree of crystallinity. Raman measurement exhibited no peak shift in E 2 (high) while a redshift in A 1 (LO) mode with rising growth temperatures, indicating the decreased of carrier concentration in the GaN nanostructures. [ABSTRACT FROM AUTHOR]

Three dimensional blood flow in compliant, tapering vessels of a truncated vascular system model containing two levels of bifurcation was investigated numerically using a commercially available finite element analysis and simulation software. Although the branching pattern and the geometry of the human vascular system are complex, they can be specified for small arteries using Murray's hypothesis that the structure of the vascular system obeys the principle of minimum work. Accordingly, in the current vascular system model, the parent/daughter diameter ratios and the angles of bifurcation were specified according to Murray's law. Another geometrical parameter, the ratio of blood vessel length to diameter, was determined according to data found in the literature. The vascular system model also includes a 5 mm thick layer of tissue surrounding the vessels. This tissue layer helps to resist artery deformation during the cardiac cycle. Experimentally measured time dependent blood velocity data, available in the literature, were used as the inlet boundary condition to represent the cardiac cycle. An outflow boundary model, consisting of an elastic tube followed by a contraction tube, was used at the four outlets to represent both the compliance and the pressure drop of the small arteries, arterioles, and capillaries that would follow the truncated vascular system. The results show that, at each bifurcation, the blood flow velocity decreases significantly in the transition from the parent vessel to the daughter vessels due to the higher total cross-sectional area of the daughter vessels as compared to the parent vessel. This decrease in velocity is partially recovered along the arteries due to the tapering of the blood vessels. It can also be observed from the results that the pressure distributions and pressure drops along the vascular system are in good agreement with the physiological data found in the literature. The results also show that the velocity profiles immediately following a bifurcation are not initially symmetric, with their maxima shifted toward the inner part of the bifurcation in the daughter vessels. Finally, the results show that the maximum deformation is about 2% of the average vessel radius, which is relatively small and typical for small arteries. [ABSTRACT FROM AUTHOR]

We describe a new procedure for making recessed tips on multimode optical glass fibers. The method is based on etching fiber tips in 40% hydrofluoric acid for defined immersion times. As the etching velocity decreases radially from the core center in multimode graded index fibers, a recess can be formed in the tip of flat-cut tapered or untapered fibers. Etched fiber tips showed improved focussing of excitation light coupled into the fiber at the opposite end, and very efficient excitation of thin layers of optical indicators immobilized into the recess. The sensor chemistry is well protected when immobilized in recessed fiber tips and allows the construction of O 2 microoptodes with improved mechanical stability that can measure repeatedly even in very cohesive biofilms, tissue and dry soil. [ABSTRACT FROM AUTHOR]

This article gives a narrative overview of what constitutes climatological data and their typical features, with a focus on aspects relevant to statistical modeling. We restrict the discussion to univariate spatial fields and focus on maximum likelihood estimation. To address the problem of enormous datasets, we study three common approximation schemes: tapering, direct misspecification, and composite likelihood for Gaussian and non-Gaussian distributions. We focus particularly on the so-called 'sinh-arcsinh distribution', obtained through a specific transformation of the Gaussian distribution. Because it has flexible marginal distributions – possibly skewed and/or heavy-tailed – it has a wide range of applications. One appealing property of the transformation involved is the existence of an explicit inverse transformation that makes likelihood-based methods straightforward. We describe a simulation study illustrating the effects of the different approximation schemes. To the best of our knowledge, a direct comparison of tapering, direct misspecification, and composite likelihood has never been made previously, and we show that direct misspecification is inferior. In some metrics, composite likelihood has a minor advantage over tapering. We use the estimation approaches to model a high-resolution global climate change field. All simulation code is available as a Docker container and is thus fully reproducible. Additionally, the present article describes where and how to get various climate datasets. • We present a short overview of climatological data and spatial statistics' uses in climatological data analysis. • We introduce the so-called 'sinh-arcsinh processes', based on a transformation having an explicit inverse. • We discuss different likelihood estimation approaches for large spatial datasets which are suited for climatological data. • We compare tapering, direct misspecification, and composite likelihood estimation in a simulation study. [ABSTRACT FROM AUTHOR]

We summarize advances in empirical likelihood (EL) for time series data. The EL formulation for independent data is briefly presented, which can apply for inference in special time series problems, reproducing the Wilks phenomenon of chi-square limits for log-ratio statistics. For more general inference with time series, versions of time domain block-based EL, and its generalizations based on divergence measures, are described along with their distributional properties; some approaches are intended for mixing time processes and others are tailored to time series with a Markovian structure. We also present frequency domain EL methods based on the periodogram. Finally, EL for long-range dependent processes is reviewed as well as recent advantages in EL for high dimensional problems. Some illustrative numerical examples are given along with a summary of open research issues for EL with dependent data. [ABSTRACT FROM AUTHOR]

Abstract: To improve safety and serviceability of super-tall buildings in strong winds, aerodynamic optimization of building shapes is considered to be the most efficient approach. Aerodynamic optimization is aimed at solving the problem from the source in contrast to structural optimization which is aimed at increasing the structural resistance against winds. However, there are two challenges that usually limit the applicability of aerodynamic optimization in design practice. One is a potential conflict between optimization schemes and other design aspects, and another is a potential conflict between cost and effectiveness. To minimize these conflicts, it is important to conduct aerodynamic studies in early design stage to gain reasonable assessment on various optimization options. This paper summarizes the aerodynamic approaches that have been used with success in building designs, and discusses the principles and effectiveness of these approaches. To provide a guideline for preliminary design, this paper proposes a practical approach to assess the effectiveness of tapering, twisting and stepping, the three common schemes of aerodynamic optimization in super-tall building design. [Copyright &y& Elsevier]

Abstract: Applying the finite element analysis on the photonic band-gap materials with a cavity at the center for two types of structures, circular and square shape holes with the same cross section, filtering operation of these structures is simulated and compared. Any variations in the structure parameters, such as cavity length, period and hole dimensions, change the transmission peak and frequency bandwidth of these structures. The effects of rotation of square holes and ellipticity of circular holes on filtering operation are studied. Other new structures such as tapered, shortened and non-uniform rotated structures are proposed and filtering characteristics of them are discussed. It is found that, by rotating the square holes around their axis, it is possible to have a blue-shift in the transmission peak wavelength without notable variations in the filter peak and bandwidth. It is concluded that the increase of elliptical holes diameters length causes the decrease of transmission peak and increase of bandwidth with blueshift of the peak wavelength. This shift is larger for one of the elliptical diameter values considered that is along the waveguide length. [Copyright &y& Elsevier]

Background: While reduced exposure to prescription opioids may decrease risks, including overdose and opioid use disorder, abrupt tapering or discontinuation may pose new risks.Objectives: To examine potentially unsafe tapering and discontinuation among dosage changes in opioid prescriptions dispensed to US patients on high-dose long-term opioid therapy.Design: Longitudinal observational study of adults (≥18 years) on stable high-dose (≥50 oral morphine milligram equivalents [MME] daily dosage) long-term opioid therapy during a 180-day baseline and a 360-day follow-up using all-payer pharmaceutical claims data, 2017-2019.Measures: Dosage tapering, increases, and/or stability during follow-up; sustained dosage stability, reductions, or discontinuation at the end of follow-up; and tapering rate. Patients could experience more than one outcome during follow-up.Results: Among 595,078 patients receiving high-dose long-term opioid therapy in the sample, 26.7% experienced sustained dosage reductions and 9.3% experienced discontinuation. Among patients experiencing tapering, 62.0% experienced maximum taper rates between > 10-40% reductions per month and 36.1% experienced monthly rates ≥ 40%. Among patients with mean baseline daily dosages ≥ 150 MME, 47.7% experienced a maximum taper rate ≥ 40% per month. Relative to baseline, 19.7% of patients experiencing tapering had long-term dosage reductions ≥ 40% per month at the end of follow-up.Implications: Dosage changes for patients on high-dose long-term opioid therapy may warrant special attention, particularly over shorter intervals, to understand how potentially sudden tapering and discontinuation can be reduced while emphasizing patient safety and shared decision-making. Rapid discontinuation of opioids can increase risk of adverse outcomes including opioid withdrawal. [ABSTRACT FROM AUTHOR]

• 16 patients tapered steroids while receiving open-label satralizumab. • Three patients discontinued steroids and remained relapse free. • Two patients relapsed (no lasting change in EDSS score) and remained in the trial. • The annualized relapse rate did not increase from the double-blind period. • The safety profile of satralizumab was comparable with the ITT population. Neuromyelitis optica spectrum disorder (NMOSD) is a rare, chronic, autoimmune disease, characterized by astrocytopathic lesions in the central nervous system (Beekman et al., 2019 ; Fujihara et al., 2020). The main aim of NMOSD maintenance therapy is to reduce the frequency and severity of relapses and minimize future disability (Fujihara et al., 2020). Oral corticosteroids are used long-term to prevent relapses, but are associated with serious complications (Kessler et al., 2016 ; Kimbrough et al., 2012). In the SAkuraSky study, satralizumab reduced the risk of relapse in patients with NMOSD compared with placebo, with comparable rates of serious adverse events and infections between treatment arms (Yamamura et al., 2019). Here, we report on 16 patients who tapered their steroid dose during the openlabel extension (OLE) period of SAkuraSky. SAkuraSky was a phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study of satralizumab in combination with immunosuppressive therapies (ISTs) in patients with NMOSD. Patients were randomized 1:1 to receive 120 mg subcutaneous satralizumab or placebo in addition to a stable dose of their baseline IST. After completing the DB period or experiencing relapse, patients could enter the OLE period. In the OLE, all patients received satralizumab, and IST doses could be tapered at the investigator's discretion. We assessed the different steroid tapering patterns and their impact on relapse and safety. Patients were considered to have tapered their steroids if their steroid dose at the clinical cut-off date (CCOD: February 18, 2020) was lower than on the first day of the OLE. Annualized relapse rate (ARR) was calculated as the number of relapses divided by the total number of patientyears at risk. Overall, 36 patients receiving oral corticosteroids entered the OLE, of whom 16 tapered their steroid dose. The mean age (range) at baseline was 44.9 (16–73) years, all 16 were female, 14 (88%) were Japanese, and 15 (94%) were AQP4-IgG seropositive. None were receiving any additional ISTs. Patients tapered their steroids from a median of 10 (range: 5–25) mg/day at OLE baseline to 2.75 (0–15) mg/day at the CCOD. Three patients discontinued steroids entirely, and all three remained relapse free. One patient who remained relapse free had temporary increases in steroid dose. Three relapses were observed in two patients who tapered steroids during the OLE; all three relapses required treatment. One of the relapses occurred shortly after a drop in steroid dose from 25 to 10 mg/day. The ARR for steroid-tapered patients was numerically lower in the OLE period than the satralizumab group in the DB period. The safety profile of satralizumab was in line with the overall SAkuraSky population. Two serious infections were observed in steroid-tapered patients in the OLE, both in the same patient: one event (hepatitis E) occurred before the patient began tapering their steroid dose; and one event (influenza) occurred while the patient was tapering. During the OLE of SAkuraSky, 16 patients tapered steroids and the ARR did not increase from the DB period. Patient numbers limit interpretation. [ABSTRACT FROM AUTHOR]

Abstract: We consider asymptotic distributions of maximum deviations of sample covariance matrices, a fundamental problem in high-dimensional inference of covariances. Under mild dependence conditions on the entries of the data matrices, we establish the Gumbel convergence of the maximum deviations. Our result substantially generalizes earlier ones where the entries are assumed to be independent and identically distributed, and it provides a theoretical foundation for high-dimensional simultaneous inference of covariances. [Copyright &y& Elsevier]

Abstract: We study the efficiency of semiparametric estimates of memory parameter. We propose a class of shift invariant tapers of order (p,q). For a fixed p, the variance inflation factor of the new tapers approaches 1 as q goes to infinity. We show that for , the proposed tapered Gaussian semiparametric estimator has the same limiting distribution as the nontapered version for . The new estimator is mean and polynomial trend invariant, and is computationally advantageous in comparison to the recently proposed exact local Whittle estimator. The simulation study shows that our estimator has comparable or better mean squared error in finite samples for a variety of models. [ABSTRACT FROM AUTHOR]

Abstract: Bile-stained vomiting in a neonate indicates significant pathology and suggests mechanical obstruction. Congenital discontinuity of the bowel (atresia) is a common cause of mechanical intestinal obstruction in neonates. Key features of duodenal/intestinal atresia and their management are discussed in this article. [Copyright &y& Elsevier]

Abstract: The use of composite materials for strengthening and repair of steel structures has attracted a great deal of attention during the last years. In this paper, the research work conducted at Chalmers University of technology during the last five years in this field is reviewed. The results from various types of tests are summarized and discussed. Aspects related to stress analysis of adhesive joints, joint modification and failure modes in steel elements strengthened with bonded CFRP-laminates are discussed. Research needs within the studied problems are also highlighted. [Copyright &y& Elsevier]

Abstract: To restore the orthogonality of the spreading code, an equalizer is adopted at the receiving site for a HSDPA system. In this paper, BER performance and complexity analysis of various equalizers are compared under different outdoor channels. Results show that with tapering technique, the fast FFT-circulant and Expand-truncate equalizers can ease the condition number problem at a high SNR multipath channel. Simulations also show that the CG method has a satisfactory BER improvement. However, its performance depends notably on the number of iterations. [Copyright &y& Elsevier]

Abstract: One major problem when using bonded Fiber Reinforced Polymer laminates is the presence of high interfacial stresses near the end of the composite laminate which might govern the failure of the strengthening schedule. A method that has been proposed for reducing the magnitude of the interfacial stresses is laminate end tapering, which can be used with or without adhesive fillets. In this paper, a comprehensive FE study has been conducted to investigate the effect of using normal and reverse tapering with and without adhesive fillets on the interfacial stress distribution in the adhesive joints at different locations, including the mid-thickness of the adhesive layer, as well as interfaces. The results indicate that using the correct combination of tapering and adhesive fillet can reduce the magnitude of the interfacial stresses significantly. However, the inappropriate use of tapering and adhesive fillets might cause higher stresses than those in joints without geometrical modification. [Copyright &y& Elsevier]

Abstract: Smoothed nonparametric kernel spectral density estimates are considered for stationary data observed on a d-dimensional lattice. The implications for edge effect bias of the choice of kernel and bandwidth are considered. Under some circumstances the bias can be dominated by the edge effect. We show that this problem can be mitigated by tapering. Some extensions and related issues are discussed. [Copyright &y& Elsevier]

Abstract: Background: To evaluate the differences between the immediate and tapered cessation protocols of hormone therapy in terms of recurrence of menopausal symptoms. Materials and methods: In this prospective, randomized clinical study 70 consecutive patients in whom hormone therapy was no longer preferred were recruited from the menopause clinic of a university hospital and rank randomized into two groups. In group 1 (n =35) hormone therapy was immediately discontinued and in group 2 (n =35) the medication was tapered. Every patient was questioned about vasomotor symptoms before the initiation of hormone therapy at the first visit, and then revisited at the end of 2 and 4 weeks. Results: We did not find any statistically significant difference between two protocols in terms of symptom severity and frequency at the end of 2 and 4 weeks of discontinuation. Although statistically insignificant, the symptoms tended to recur in fewer patients and in a less severe form in both groups when compared with their pretreatment status. Conclusions: Tapering or immediate discontinuing of hormone therapy did not affect the recurrence rate and severity of menopausal symptoms at the end of 4 weeks. [Copyright &y& Elsevier]

Abstract: Objectives: Reimplantation of megaureters may be complicated by excessive bulk of tissue when plicated, or stenosis at the anastomosis site when excisional tapering is performed. Some urologists in our institution reimplant megaureters without tailoring, while others routinely tailor megaureters. Aiming to compare success rates, we report our experience in reimplanting obstructive megaureters with and without tailoring. Materials: The medical records of 30 boys and four girls with primary obstructive megaureters (a total of 38 ureters) were reviewed. Median age at operation was 18 months (range 1 month to 8 years). Of the ureters, 16/38 were tailored and 22/38 were reimplanted without tailoring. Results: Preoperative mean diameter (per ultrasound) of the 16 tailored ureters was 16.1mm (range 10–26mm). Postoperative ultrasound showed resolution of hydronephrosis in 3/16 (19%), an improvement in 11/16 (69%), and no change in the degree of hydronephrosis in 2/16 (13%). Preoperative mean diameter of the non-tailored ureters was 14mm (range 10–27mm), and postoperative ultrasound showed resolution of hydronephrosis in 11/22 (50%), an improvement in 10/22 (45%), and no change in the degree of hydronephrosis in 1/22 (5%). Of the tailored ureters, 1/16 needed re-operation because of anastomotic stricture, and one girl had recurrent urinary tract infections. Of the non-tailored ureters, four had recurrent infection, of whom one boy underwent redo reimplantation because of grade 2 vesicoureteric reflux. Conclusion: In this series non-tailoring reimplantation was an equivalent option to tailoring in obstructive megaureters. [Copyright &y& Elsevier]

Long term use of immunosuppressants impacts the cardiovascular system and increases the risk of infection and malignancy. To effectively reduce immunosuppression in a transplant recipient a tool is needed to directly monitor the level of immune function. The Cylex® Immune Cell Function Assay, approved by the FDA for the assessment of cell-mediated immunity, shows promise as an objective measure of a transplant recipient's immune function. In a blinded retrospective study, the immune function was compared to clinical courses and histological examinations of biopsies of 20 small bowel transplant recipients during periods of immunosuppressant tapering. Eight patients with no major adverse events or changes of immunosuppressive therapy had moderate to low immune function and were categorized as immunologically and clinically stable. Twelve patients displaying strong immune responses were immunologically and clinically volatile requiring addition of steroids and or OKT3. Results validate the clinical utility of the Cylex Immune Cell Function Assay as an objective too for assessing immune function. By evaluating immune function, physicians now can identify those patients who are candidates for minimization of immunosuppressant therapy, manage the timing and rate of immunosuppressant weaning and be forewarned of increased patient risk. [ABSTRACT FROM AUTHOR]

The aim of the present work is to investigate the influence of a tapered undulator on the main parameters of an free electron laser (FEL). The experiments were carried out at the Darmstadt FEL at an electron beam energy of 31 MeV and a wavelength of 7 μm. The effect of tapering depth on various important free electron laser characteristics such as the wavelength corresponding to the peak of the spectral distribution, the spectral width, the small signal gain and the electron energy extraction efficiency has been experimentally observed and quantitatively understood. It is shown for example that the wavelength shift is well described taking into account short pulse effects. Furthermore, for the first time, it has been found that for some values of the tapering depth the FEL efficiency exceeds that of the uniform undulator by more than 35% and 18% for negative and positive tapering, respectively. The experimental data of the spectral distributions for different tapering values are compared with predictions based on simulations for the interaction processes in the tapered undulator and with the experimental results recently obtained at the IR DEMO FEL at the Thomas Jefferson National Accelerator Facility. [Copyright &y& Elsevier]

Tapering process of WEDM, which can generate curved surfaces on workpiece, is a very unique ability of this machining process. This report is dedicated to the removal analysis of tapering WEDM and to the improvement of contouring accuracy in application to conjugate surfaces. An inclined discharge angle (IDA) analysis was proposed to study the removal mechanism with a novel point of view. Based upon the analysis, a theoretical removal model was proposed. Furthermore, it might be reasonable that the machining load and contouring error could be inferred from the removal burden. Therefore, an improvement strategy including control of discharged power and wire tension was proposed to adapt to the variation of machining load. Effects of the proposed method were verified through experiments. It is evident that the tapering accuracy was improved significantly, and it is feasible to the generation of precise conjugate surface. [Copyright &y& Elsevier]

This paper is concerned with the inelastic local buckling of flat plate structures that contain plates with variable thicknesses. Use is made of the semi-analytical complex finite strip method, which is augmented with transverse bubble functions. Stiffness and stability matrices are derived for inclusion in the finite strip method, which is based on the deformation theory of plasticity. The numerical scheme is programmed, and several numerical examples are presented to illustrate the prowess and scope of the procedure. The inelastic local buckling of tapered plates subjected to compression and shear with different boundary conditions is studied first, and the method is then applied to the inelastic local buckling of channel sections with tapered flanges and stiffened plates with variable thickness and different geometries. Slenderness limits for channels that delineate between local buckling and yield (and that define the transition from non-compact to slender cross-sections) are discussed. [Copyright &y& Elsevier]