Reduction Of Group Research Articles

Post-implantation analysis of genomic variations in the progeny from developing fetus to birth

The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families’ blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17–58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70–82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59–54.20) and 51.09 (49.22–52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P < 0.001). The average number of de novo indels among the multifetal reduction group and the newborn group was 26.26 (23.27–29.05) and 5.17 (4.82–5.52), respectively. To conclude, it has been observed that the quantity of de novo indels in the newborns experiences a significant decrease when compared to that in the aspirated embryonic tissues (7–9 weeks). This phenomenon is evident across all genomic regions, highlighting the adverse effects of de novo indels on the fetus and emphasizing the significance of embryonic implantation and intrauterine growth in human genetic selection mechanisms.

A comparison of endomorphism algebras

Let F be a non-archimedean local field and G be a connected reductive group over F. For a Bernstein block in the category of smooth complex representations of G(F), we have two kinds of progenerators: the compactly induced representation indKG(F)(ρ) of a type (K,ρ), and the parabolically induced representation IPG(ΠM) of a progenerator ΠM of a Bernstein block for a Levi subgroup M of G. In this paper, we construct an explicit isomorphism of these two progenerators. Moreover, we compare the description of the endomorphism algebra EndG(F)(indKG(F)(ρ)) for a depth-zero type (K,ρ) in [20] with the description of the endomorphism algebra EndG(F)(IPG(ΠM)) in [33], that are described in terms of affine Hecke algebras.

127 Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in Heart Failure with Reduced Ejection Fraction Patients: A Systematic Review and Meta-Analysis Stratified by Left Ventricular Ejection Fraction

Abstract Aim The primary objectives were to assess differences in mortality, repeat revascularization, new postoperative myocardial infarction (MI), and cerebrovascular accidents (CVA/stroke) between PCI and CABG in HFrEF patients, stratified by the degree of LVEF reduction. Method A comprehensive search of electronic databases was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria comprised clinical trials or observational cohort studies with ≥20 patients per group, comparing long-term outcomes in HFrEF patients (LVEF &amp;lt;50%) who underwent PCI or CABG. Data was extracted, and quality was assessed using the New Castle Ottawa (NOS) Risk of Bias tool. Hazard ratios (HRs) were pooled for time-to-event outcomes, with subgroup analysis based on LVEF. Heterogeneity was assessed, sensitivity analysis conducted, and publication bias evaluated. Results Twenty studies involving 25,031 patients met the inclusion criteria. In the severe LVEF reduction group (&amp;lt;35%), CABG was associated with significantly higher long-term survival, reduced repeat revascularization, and fewer postoperative MIs compared to PCI. In patients with moderate LVEF reduction (&amp;lt;40%), there was no difference in long-term survival, but repeat revascularization was lower in the CABG group . In the mild LVEF reduction group (&amp;lt;50%), CABG was associated with superior long-term survival and reduced repeat revascularization. Stroke rates were similar between PCI and CABG in all groups. Conclusions Individualized patient care should consider the degree of LVEF reduction when selecting between PCI and CABG, with CABG generally favored for improved outcomes in HFrEF patients. However, clinical presentation, patient characteristics, and cost-effectiveness should also be considered in the decision-making process.

A Hilbert–Mumford criterion for polystability for actions of real reductive Lie groups

AbstractWe study a Hilbert–Mumford criterion for polystablility associated with an action of a real reductive Lie group G on a real submanifold X of a Kähler manifold Z. Suppose the action of a compact Lie group with Lie algebra $$\mathfrak {u}$$ u extends holomorphically to an action of the complexified group $$U^{\mathbb {C}}$$ U C and that the U-action on Z is Hamiltonian. If $$G\subset U^{\mathbb {C}}$$ G ⊂ U C is compatible, there is a corresponding gradient map $$\mu _\mathfrak {p}: X\rightarrow \mathfrak {p}$$ μ p : X → p , where $$\mathfrak {g}= \mathfrak {k}\oplus \mathfrak {p}$$ g = k ⊕ p is a Cartan decomposition of the Lie algebra of G. Under some mild restrictions on the G-action on X, we characterize which G-orbits in X intersect $$\mu _\mathfrak {p}^{-1}(0)$$ μ p - 1 ( 0 ) in terms of the maximal weight functions, which we viewed as a collection of maps defined on the boundary at infinity ($$\partial _\infty G/K$$ ∂ ∞ G / K ) of the symmetric space G/K. We also establish the Hilbert–Mumford criterion for polystability of the action of G on measures.

Reducing Central Nervous System–Active Medications to Prevent Falls and Injuries Among Older Adults

High-risk medications that contribute to adverse health outcomes are frequently prescribed to older adults. Deprescribing interventions reduce their use, but studies are often not designed to examine effects on patient-relevant health outcomes. To test the effect of a health system-embedded deprescribing intervention targeting older adults and their primary care clinicians for reducing the use of central nervous system-active drugs and preventing medically treated falls. In this cluster randomized, parallel-group, clinical trial, 18 primary care practices from an integrated health care delivery system in Washington state were recruited from April 1, 2021, to June 16, 2022, to participate, along with their eligible patients. Randomization occurred at the clinic level. Patients were community-dwelling adults aged 60 years or older, prescribed at least 1 medication from any of 5 targeted medication classes (opioids, sedative-hypnotics, skeletal muscle relaxants, tricyclic antidepressants, and first-generation antihistamines) for at least 3 consecutive months. Patient education and clinician decision support. Control arm participants received usual care. The primary outcome was medically treated falls. Secondary outcomes included medication discontinuation, sustained medication discontinuation, and dose reduction of any and each target medication. Serious adverse drug withdrawal events involving opioids or sedative-hypnotics were the main safety outcome. Analyses were conducted using intent-to-treat analysis. Among 2367 patient participants (mean [SD] age, 70.6 [7.6] years; 1488 women [63%]), the adjusted cumulative incidence rate of a first medically treated fall at 18 months was 0.33 (95% CI, 0.29-0.37) in the intervention group and 0.30 (95% CI, 0.27-0.34) in the usual care group (estimated adjusted hazard ratio, 1.11 (95% CI, 0.94-1.31) (P = .11). There were significant differences favoring the intervention group in discontinuation, sustained discontinuation, and dose reduction of tricyclic antidepressants at 6 months (discontinuation adjusted rate: intervention group, 0.23 [95% CI, 0.18-0.28] vs usual care group, 0.13 [95% CI, 0.09-0.17]; adjusted relative risk, 1.79 [95% CI, 1.29-2.50]; P = .001) and secondary time points (9, 12, and 15 months). In this randomized clinical trial of a health system-embedded deprescribing intervention targeting community-dwelling older adults prescribed central nervous system-active medications and their primary care clinicians, the intervention was no more effective than usual care in reducing medically treated falls. For health systems that attend to deprescribing as part of routine clinical practice, additional interventions may confer modest benefits on prescribing without a measurable effect on clinical outcomes. ClinicalTrials.gov Identifier: NCT05689554.

A Stone–von Neumann equivalence of categories for smooth representations of the Heisenberg group

The classical Stone–von Neumann theorem relates the irreducible unitary representations of the Heisenberg group Hn to non-trivial unitary characters of its center Z, and plays a crucial role in the construction of the oscillator representation for the metaplectic group. In this paper we extend these ideas to non-unitary and non-irreducible representations, thereby obtaining an equivalence of categories between certain representations of Z and those of Hn. Our main result is a smooth equivalence, which involves the fundamental ideas of du Cloux on differentiable representations and smooth imprimitivity systems for Nash groups. We show how to extend the oscillator representation to the smooth setting and give an application to degenerate Whittaker models for representations of reductive groups. We also include an algebraic equivalence, which can be regarded as a generalization of Kashiwara’s lemma from the theory of D-modules.

Screen Media Use and Mental Health of Children and Adolescents

Excessive screen media use has been associated with poorer mental health among children and adolescents in several observational studies. However, experimental evidence supporting this hypothesis is lacking. To investigate the effects of a 2-week screen media reduction intervention on children's and adolescents' mental health. This prespecified secondary analysis of a cluster randomized clinical trial with a 2-week follow-up included 89 families (with 181 children and adolescents) from 10 Danish municipalities in the region of Southern Denmark. All study procedures were carried out in the home of the participants. Enrollment began on June 6, 2019, and ended on March 30, 2021. This analysis was conducted between January 1 and November 30, 2023. Families were randomly allocated to a screen media reduction group or a control group. The 2-week screen media reduction intervention was designed to ensure a high level of compliance to the reduction in leisure-time screen media use. Participants allocated to the intervention group had to reduce their leisure-time screen media use to 3 hours per week or less per person and hand over smartphones and tablets. The main outcome was the between-group mean difference in change in total behavioral difficulties, measured by the Strengths and Difficulties Questionnaire at 2-week follow-up. Results were estimated using mixed-effects tobit regression models. Analyses were carried out as both intention to treat and complete case. In the sample of 89 families including 181 children and adolescents (intervention group [45 families]: 86 children; mean [SD] age, 8.6 [2.7] years; 42 girls [49%]; control group [44 families]: 95 children; mean [SD] age, 9.5 [2.5] years; 57 girls [60%]), there was a statistically significant between-group mean difference in the total difficulties score, favoring the screen media reduction intervention (-1.67; 95% CI, -2.68 to -0.67; Cohen d, 0.53). The greatest improvements were observed for internalizing symptoms (emotional symptoms and peer problems; between-group mean difference, -1.03; 95% CI, -1.76 to -0.29) and prosocial behavior (between-group mean difference, 0.84; 95% CI, 0.39-1.30). This secondary analysis of a randomized clinical trial found that a short-term reduction in leisure-time screen media use within families positively affected psychological symptoms of children and adolescents, particularly by mitigating internalizing behavioral issues and enhancing prosocial behavior. More research is needed to confirm whether these effects are sustainable in the long term. ClinicalTrials.gov Identifier: NCT04098913.

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

A controlled clinical study of vertebroplasty for the treatment of osteoporotic vertebral compression fractures after self-made spinal positioner and manual reduction

To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.

Reductive covers of klt varieties

In this article, we study G -covers of klt varieties, where G is a reductive group. First, we exhibit an example of a klt singularity admitting a \mathbb{P}{\mathrm{GL}}_{n}(\mathbb{K}) -cover that is not of klt type. Then, we restrict ourselves to G -quasi-torsors, a special class of G -covers that behave like G -torsors outside closed subsets of codimension two. Given a G -quasi-torsor X\rightarrow Y , where G is a finite extension of a torus \mathbb{T} , we show that X is of klt type if and only if Y is of klt type. We prove a structural theorem for \mathbb{T} -quasi-torsors over normal varieties in terms of Cox rings. As an application, we show that every sequence of \mathbb{T} -quasi-torsors over a variety with klt type singularities is eventually a sequence of \mathbb{T} -torsors. This is the torus version of a result due to Greb–Kebekus–Peternell regarding finite quasi-torsors of varieties with klt type singularities. On the contrary, we show that in any dimension there exists a sequence of finite quasi-torsors and \mathbb{T} -quasi-torsors over a klt type variety, such that infinitely many of them are not torsors. We show that every variety with klt type singularities is a quotient of a variety with canonical factorial singularities. We prove that a variety with Zariski locally toric singularities is indeed the quotient of a smooth variety by a solvable group. Finally, motivated by the work of Stibitz, we study the optimal class of singularities for which the previous results hold.

Non-commutative resolutions of linearly reductive quotient singularities

ABSTRACT We prove the existence of non-commutative crepant resolutions (in the sense of Van den Bergh) of quotient singularities by finite and linearly reductive group schemes in positive characteristic. In dimension 2, we relate these to resolutions of singularities provided by G-Hilbert schemes and F-blowups. As an application, we establish and recover results concerning resolutions for toric singularities, as well as canonical, log terminal and F-regular singularities in dimension 2.

Multiplicative Higgs bundles and involutions

In this paper we generalize the theory of multiplicative G-Higgs bundles over a curve to pairs (G,θ), where G is a reductive algebraic group and θ is an involution of G. This generalization involves the notion of a multiplicative Higgs bundle taking values in a symmetric variety associated to θ, or in an equivariant embedding of it. We also study how these objects appear as fixed points of involutions of the moduli space of multiplicative G-Higgs bundles, induced by the involution θ.

G-torsors and universal torsors over nonsplit del Pezzo surfaces

Let S be a smooth del Pezzo surface that is defined over a field K and splits over a Galois extension L. Let G be either the split reductive group given by the root system of SL in PicSL, or a form of it containing the Néron–Severi torus. Let G be the G-torsor over SL obtained by extension of structure group from a universal torsor T over SL. We prove that G does not descend to S unless T does. This is in contrast to a result of Friedman and Morgan that such G always descend to singular del Pezzo surfaces over C from their desingularizations.

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The ‘Reduction group’ involved dose reduction of tacrolimus while the ‘Conversion group’ included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3–4 and 4–5). In the iVL 4–5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3–4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.

Analysis of risk factors for failed closed reduction in pediatric Gartland Type III supracondylar humerus fracture

PurposeGartland Type III supracondylar humerus fractures are commonly treated using closed reduction followed by percutaneous pin fixation. However, conversion to open reduction may be necessary if closed reduction fails. This study aimed to identify risk factors associated with failed closed reduction and provide a theoretical basis for clinical decision-making in the treatment of Gartland Type III fractures. MethodsA retrospective analysis was conducted on children with Gartland Type III supracondylar humerus fracture who underwent surgical treatment between April 2017 and June 2018. Based on whether or not the closed reduction was successful, patients were split into the open reduction group and the closed reduction group. Within the closed reduction group, subgroup analysis based on surgery duration was carried out. Data were collected from medical records and X-ray images. Univariate and multivariate regression analyses were utilized to evaluate the relationship between variables and failed closed reduction. ResultsThe study included 36 patients in the open reduction group and 135 patients in the closed reduction group. Multivariate analysis revealed that the presence of angle (P=0.024, OR=3.199), rotation (P=0.000, OR=6.359), skin creases (P=0.013, OR=4.077), anterior-posterior displacement ratio (P=0.011, OR=4.337), fracture angle in the anteroposterior view (P=0.014, OR=0.939), and fracture distal displacement direction (P=0.002, OR=5.384) were independent risk factors for failed closed reduction. Subgroup analysis showed that fracture distal displacement direction (P=0.013), skin folds (P=0.013), lateral displacement ratio (P=0.016), and anterior-posterior displacement value (P=0.005) significantly influenced the duration of closed reduction surgery. ConclusionThe presence of sharp angle or rotation at the fracture ends, skin folds on the anterior elbow, minor anterior-posterior displacement of the fracture, higher medial inclination of the fracture plane, and distal fracture displacement towards the radial side are independent risk factors for failed closed reduction in pediatric Gartland Type III supracondylar humerus fracture.

Effectiveness of Mindfulness-based Stress Reduction Group Training on Resilience and high-risk Behaviors of Students with Self-harm Experience in Raz and Jorglan Cities

Effectiveness of Mindfulness-based Stress Reduction Group Training on Resilience and high-risk Behaviors of Students with Self-harm Experience in Raz and Jorglan Cities

Global liftings between inner forms of GSp(4)

For reductive groups G over a number field we discuss automorphic liftings of cohomological cuspidal irreducible automorphic representations π of G(A) to irreducible cohomological automorphic representations of H(A) for the quasi-split inner form H of G, and other inner forms as well. We show the existence of nontrivial weak global cohomological liftings in many cases, in particular for the case where G is anisotropic at the archimedean places. A priori, for these weak liftings we do not give a description of the precise nature of the corresponding local liftings at the ramified places, nor do we characterize the image of the lifting. For inner forms of the group H=GSp(4) however we address these finer questions. Especially, we prove the recent conjectures of Ibukiyama and Kitayama on paramodular newforms of square-free level.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

Twisted Whittaker category on affine flags and the category of representations of the mixed quantum group

Let $G$ be a reductive group, and let $\check {G}$ be its Langlands dual group. Arkhipov and Bezrukavnikov proved that the Whittaker category on the affine flags ${\operatorname {Fl}}_G$ is equivalent to the category of $\check {G}$ -equivariant quasi-coherent sheaves on the Springer resolution of the nilpotent cone. This paper proves this theorem in the quantum case. We show that the twisted Whittaker category on ${\operatorname {Fl}}_G$ and the category of representations of the mixed quantum group are equivalent. In particular, we prove that the quantum category $\mathsf {O}$ is equivalent to the twisted Whittaker category on ${\operatorname {Fl}}_G$ in the generic case. The strong version of our main theorem claims a motivic equivalence between the Whittaker category on ${\operatorname {Fl}}_G$ and a factorization module category, which holds in the de Rham setting, the Betti setting, and the $\ell$ -adic setting.