Effect of rLH Supplementation during Controlled Ovarian Stimulation for IVF: Evidence from a Retrospective Analysis of 1470 Poor/Suboptimal/Normal Responders Receiving Either rFSH plus rLH or rFSH Alone

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification

Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy

Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV‐infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 ‘Pre-Pandemic’, 28 ‘Pandemic’) using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 (‘Pre-Pandemic’ cLBP) or between August 2020 and May 2022 (‘Pandemic’ cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r’s ≥ 0.35; P’s < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = −0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself

Ferromagnetic/superconducting proximity effect in La0.7Ca0.3MnO3 / YBa2Cu3O7 superlattices

We study the interplay between magnetism and superconductivity in high quality YBa2Cu3O7 (YBCO) / La0.7Ca0.3MnO3(LCMO)superlattices. We find evidence for the YBCO superconductivity depression in presence of the LCMO layers. We show that due to its short coherence length superconductivity survives in the YBCO down to much smaller thickness in presence of the magnetic layer than in low Tc superconductors. We also find that for a fixed thickness of the superconducting layer, superconductivity is depressed over a thickness interval of the magnetic layer in the 100 nm range. This is a much longer length scale than that predicted by the theory of ferromagnetic/superconducting proximity effect.Comment: 10 pages + 5 figures, submitted to Phys. Rev.

Microwave Electrodynamics of Electron-Doped Cuprate Superconductors

We report microwave cavity perturbation measurements of the temperature dependence of the penetration depth, lambda(T), and conductivity, sigma(T) of Pr_{2-x}Ce_{x}CuO_{4-delta} (PCCO) crystals, as well as parallel-plate resonator measurements of lambda(T) in PCCO thin films. Penetration depth measurements are also presented for a Nd_{2-x}Ce_{x}CuO_{4-delta} (NCCO) crystal. We find that delta-lambda(T) has a power-law behavior for T<T_c/3, and conclude that the electron-doped cuprate superconductors have nodes in the superconducting gap. Furthermore, using the surface impedance, we have derived the real part of the conductivity, sigma_1(T), below T_c and found a behavior similar to that observed in hole-doped cuprates.Comment: 4 pages, 4 figures, 1 table. Submitted to Physical Review Letters revised version: new figures, sample characteristics added to table, general clarification give

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings

Crossed Andreev reflection at ferromagnetic domain walls

We investigate several factors controlling the physics of hybrid structures involving ferromagnetic domain walls (DWs) and superconducting (S) metals. We discuss the role of non collinear magnetizations in S/DW junctions in a spin $\otimes$ Nambu $\otimes$ Keldysh formalism. We discuss transport in S/DW/N and S/DW/S junctions in the presence of inelastic scattering in the domain wall. In this case transport properties are similar for the S/DW/S and S/DW/N junctions and are controlled by sequential tunneling of spatially separated Cooper pairs across the domain wall. In the absence of inelastic scattering we find that a Josephson current circulates only if the size of the ferromagnetic region is smaller than the elastic mean free path meaning that the Josephson effect associated to crossed Andreev reflection cannot be observed under usual experimental conditions. Nevertheless a finite dc current can circulate across the S/DW/S junction due to crossed Andreev reflection associated to sequential tunneling.Comment: 18 pages, 8 figures, references added at the end of the introductio

Existence and regularity results for solutions to nonlinear parabolic equations

We prove existence and regularity result for a class of parabolic equations whose data belongs to the classical space-time space