Hierarchical Phased-Array Antennas Coupled to Al KIDs: A Scalable Architecture for Multi-band Millimeter/Submillimeter Focal Planes.

We present the optical characterization of two-scale hierarchical phased-array antenna kinetic inductance detectors (KIDs) for millimeter/submillimeter wavelengths. Our KIDs have a lumped-element architecture with parallel plate capacitors and aluminum inductors. The incoming light is received with a hierarchical phased array of slot dipole antennas, split into 4 frequency bands (between 125 GHz and 365 GHz) with on-chip lumped-element band-pass filters, and routed to different KIDs using microstriplines. Individual pixels detect light for the 3 higher-frequency bands (190-365 GHz), and the signals from four individual pixels are coherently summed to create a larger pixel detecting light for the lowest frequency band (125-175 GHz). The spectral response of the band-pass filters was measured using Fourier transform spectroscopy (FTS), the far-field beam pattern of the phased-array antennas was obtained using an infrared source mounted on a 2-axis translating stage, and the optical efficiency of the KIDs was characterized by observing loads at 294 K and 77 K. We report on the results of these three measurements.

Economic evaluation of doravirine/tenofovir disoproxil fumarate/lamivudine for HIV-1-infected adults in Russia: a cost-minimization and budget impact analysis.

BACKGROUND: In Russia, before 2022, the list of vital and essential drugs for HIV-infected patients previously untreated with antiretroviral drugs included the fixed-dose combination rilpivirine/tenofovir disoproxil fumarate/emtricitabine (RPV/TDF/FTC) but not doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/TDF/3TC). METHODS: An indirect comparison of the efficacy of DOR/TDF/3TC and RPV/TDF/FTC defined by virologic suppression (HIV-1 RNA of <50 copies/mL at week 48) was made. The per-patient drug costs over 1 year were compared in a cost-minimization analysis. A budget impact analysis considered the costs to the healthcare system of including DOR/TDF/3TC as a treatment option for eligible patients in Russia over a 3-year time horizon. RESULTS: The indirect treatment comparison of DOR/TDF/3TC and RPV/TDF/FTC in treatment-naïve patients with baseline HIV-1 RNA 100,000 copies/ml or less showed no statistically significant difference (RR 0.914, 95% CI 0.833-1.003). In the cost-minimization analysis, the per-patient cost of one year of treatment with RPV/TDF/FTC and DOR/TDF/3TC was, respectively, ₽320,975 and ₽151,192, for a saving of ₽169,783. In the budget impact analysis, the adoption of DOR/TDF/3TC into clinical practice is expected to reduce drug costs by ₽333 million (23.8%) in year 3. CONCLUSIONS: Fixed-dose combination DOR/TDF/3TC is equally effective and cost-saving compared to RPV/TDF/FTC from Russian vital and essential drugs list perspective.

Large-Area Superconducting Nanowire Single-Photon Detectors for Operation at Wavelengths up to 7.4 µm.

The optimization of superconducting thin-films has pushed the sensitivity of superconducting nanowire single-photon detectors (SNSPDs) to the mid-infrared (mid-IR). Earlier demonstrations have shown that straight tungsten silicide nanowires can achieve unity internal detection efficiency (IDE) up to λ = 10 µm. For a high system detection efficiency (SDE), the active area needs to be increased, but material nonuniformity and nanofabrication-induced constrictions make mid-IR large-area meanders challenging to yield. In this work, we improve the sensitivity of superconducting materials and optimize a high-resolution nanofabrication process to demonstrate large-area SNSPDs with unity IDE at 7.4 µm. Our approach yields large-area meanders down to 50 nm width, with average line-width roughness below 10%, and with a lower impact from constrictions compared to previous demonstrations. Our methods pave the way to high-efficiency SNSPDs in the mid-IR band with potential impacts on astronomy, imaging, and physical chemistry.

Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides.

BACKGROUND: Increases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF. METHODS: Adults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines. RESULTS: A total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents. CONCLUSIONS: TDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.

Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization.

BACKGROUND AND OBJECTIVE: Many people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice. METHODS: PLWH prescribed TDF for ≥ 4 weeks who switched to TAF were identified in the OPERA cohort. Patterns of dyslipidemia were compared before and after switch based on NCEP ATPIII guidelines. Elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD ≥ 7.5%) and statin use were assessed. RESULTS: Among 6423 PLWH switched from TDF to TAF, the proportion with dyslipidemia/severe dyslipidemia observed after switch from TDF to TAF increased statistically significantly (p < 0.0001) with total cholesterol (5-10%), low-density lipoprotein cholesterol (16-23%), and triglycerides (21-27%), but decreased statistically significantly with high-density lipoprotein cholesterol (35-30%, p < 0.0001). These patterns of dyslipidemia persisted in sensitivity analyses restricted to PLWH who maintained all other antiretrovirals (N = 4328) or stratified by pharmaco-enhancer use before and after switch. An elevated ASCVD risk was detected in 29% before and 31% after switch. As many as 59% of PLWH with an elevated ASCVD risk were not prescribed a statin after switch from TDF to TAF. CONCLUSIONS: In this large, diverse population of PLWH in the USA, the switch from TDF to TAF was associated with development of less favorable lipid profiles, regardless of pharmaco-enhancers or third-agent use. Statins remained underutilized after a switch from TDF to TAF.

Weight gain before and after switch from TDF to TAF in a U.S. cohort study.

INTRODUCTION: Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. METHODS: Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. RESULTS: A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. CONCLUSIONS: In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.

Demonstration of a Thermally Coupled Row-Column SNSPD Imaging Array.

While single-pixel superconducting nanowire single photon detectors (SNSPDs) have demonstrated remarkable efficiency and timing performance from the UV to near-IR, scaling these devices to large imaging arrays remains challenging. Here, we propose a new SNSPD multiplexing system using thermal coupling and detection correlations between two photosensitive layers of an array. Using this architecture with the channels of one layer oriented in rows and the second layer in columns, we demonstrate imaging capability in 16-pixel arrays with accurate spot tracking at the few-photon level. We also explore the performance trade-offs of orienting the top layer nanowires parallel and perpendicular to the bottom layer. The thermally coupled row-column scheme is readily able to scale to the kilopixel size with existing readout systems and, when combined with other multiplexing architectures, has the potential to enable megapixel scale SNSPD imaging arrays.

Healthcare resource utilization and costs in patients with HIV-1 who switched first-line antiretroviral therapy.

Objectives: This study compared healthcare utilization and costs associated with switching the first-line protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) based antiretroviral (ARV) regimen due to reasons other than virologic failure among patients with HIV-1. Methods: This was a retrospective analysis of commercial and Medicare Advantage with Part D enrollees in two US administrative claims databases. The study population comprised adults with HIV-1 infection initiating antiretroviral therapy (ART) on PI- or NNRTI-containing regimens from 1 January 2006 to 31 December 2015. Patients with a subsequent change in anchor agent were assigned to the switch cohort; the non-switch cohort was constructed using propensity score matching of three non-switching patients for each patient in the switch cohort. Patient characteristics and per patient per month healthcare resource utilization and costs were compared between the cohorts during the pre-switch, switch (15 days before and after switching) and post-switch periods. Costs during the switch period were also estimated with a multivariable-adjusted model. Results: The matched study population consisted of 1204 patients who switched their first-line PI- or NNRTI-based regimen and 3612 patients who did not. Compared with the non-switch cohort, patients who switched had higher healthcare resource utilization during the pre-switch, switch and post-switch periods. Mean unadjusted non-ART costs in the switch cohort were nearly double ($2944 versus $1530, p < .001), more than double ($2562 versus $1215, p < .001) and 1.5 times higher ($1473 versus $968, p < .001) than costs in the non-switch cohort in the pre-switch, switch and post-switch periods, respectively. Conclusions: Patients with HIV-1 who initiated PI- or NNRTI-based regimens and switched ARTs for reasons other than virologic failure used more healthcare resources and incurred greater costs relative to patients in the non-switch cohort. This study highlights the importance of initiating patients on appropriate first-line ART to avoid the need to switch due to reasons other than virologic failure.

Optically Addressing Single Rare-Earth Ions in a Nanophotonic Cavity.

We demonstrate optical probing of spectrally resolved single Nd^{3+} rare-earth ions in yttrium orthovanadate. The ions are coupled to a photonic crystal resonator and show strong enhancement of the optical emission rate via the Purcell effect, resulting in near radiatively limited single photon emission. The measured high coupling cooperativity between a single photon and the ion allows for the observation of coherent optical Rabi oscillations. This could enable optically controlled spin qubits, quantum logic gates, and spin-photon interfaces for future quantum networks.

Nanophotonic rare-earth quantum memory with optically controlled retrieval.

Optical quantum memories are essential elements in quantum networks for long-distance distribution of quantum entanglement. Scalable development of quantum network nodes requires on-chip qubit storage functionality with control of the readout time. We demonstrate a high-fidelity nanophotonic quantum memory based on a mesoscopic neodymium ensemble coupled to a photonic crystal cavity. The nanocavity enables >95% spin polarization for efficient initialization of the atomic frequency comb memory and time bin-selective readout through an enhanced optical Stark shift of the comb frequencies. Our solid-state memory is integrable with other chip-scale photon source and detector devices for multiplexed quantum and classical information processing at the network nodes.

Assessing the reliability and validity of a newly developed insomnia treatment satisfaction questionnaire (ITSAT-Q).

PURPOSE: To produce a valid insomnia treatment satisfaction questionnaire (ITSAT-Q) to assess treatment satisfaction with pharmacotherapy for use in patients with insomnia. PATIENTS AND METHODS: Items developed for a self-administered questionnaire were analyzed using exploratory factor analysis (EFA), which produced 5 dimensions. Confirmatory factor analysis was used to verify results from EFA, and structural equation modeling was used to test the hypothesized relationship among the dimensions. Data were collected from patients as part of a Sleep Research Project from January 2008 until October of 2008. RESULTS: Approximately 69.8% of the sample (n=298) was female. Item-to-total correlations were 0.66 for convenience, ranged from 0.52 to 0.62 for expectations, from 0.54 to 0.69 for value, from 0.50 to 0.57 for effectiveness, and from 0.58 to 0.72 for treatment satisfaction. All standardized parameter estimates from confirmatory factor analysis were significant (p<0.01). Goodness of fit measures for the final structural equation model were chi(2)=45.2 (d.f.=45); p=0.465; CFI=1.00; TLI=1.00; and RMSEA=0.004. Treatment satisfaction was a strong and significant predictor of value, and effectiveness was a strong predictor of treatment satisfaction (p<0.01). Expectations were a strong and equal predictor of both treatment satisfaction and value (p<0.001). CONCLUSION: The ITSAT-Q provided acceptable results for instrument reliability and validity. Findings from this study will provide additional insight regarding patient perceptions of treatment satisfaction and other related therapeutic dimensions to help prescribers assess pharmacotherapy.

Analysis of the impact of the Uruguay Round Agreements Act on pharmaceutical patents.

The Uruguay Round Agreements Act (URAA) was enacted by the United States Congress in 1994. The URAA provided substantial modifications to the framework for U.S. patent law that came into effect January 1, 1953. Changes in patent regulation are especially important in the pharmaceutical sector because the patent system determines, in large part, the reward that an inventor can derive from discovery of a new drug. Most pharmaceutical patents are classified as utility patents. Pharmaceutical patents may include claims for the active ingredient per se, for the formulation of the active ingredient for use as a pharmaceutical, for therapeutic indications and uses, and for methods of manufacturing the drug. The U.S. has a First-to-Invent system to establishing the right of priority of an invention, but most countries have a First-to-File priority system. The First-to-Invent system allows for public disclosure of inventions prior to patent filing. In contrast, the First-to-File system encourages early filing of patent applications. In both systems, filing an application for a patent as soon as the drug is discovered allows inventors to obtain an earlier date of invention relative to potential competitors and establish the right of priority over the invention.

The impact of allergic rhinitis on work productivity.

AIM: Patients with allergic rhinitis experience a multitude of symptoms that usually compromise some aspect of lifestyle. However, few data are available that specifically address the impact of allergic rhinitis on work productivity. METHODS: A questionnaire was developed and mailed to 2,065 patients enrolled in a 500,000-member managed care organisation. Patients were identified by diagnostic codes for allergic rhinitis as determined by a retrospective examination of medical and prescription claims records from January 1 2000 to December 31 2000. Patients were divided into three different care groups according to whether they were managed by family physicians, by allergists, or were self-managed. RESULTS: Chi-square and analysis of variance tests revealed significant differences among the three care groups (p<0.05) for years with allergies, symptoms, family history, testing, immunotherapy, test value, and prescribed antihistamine use. Multiple linear regression analysis revealed that sleep, health, certain allergy symptoms and prescribed antihistamines were significantly related to work productivity. CONCLUSIONS: The results of this study revealed that the ability of individuals with allergic rhinitis to engage in productive work is influenced by sleep, health-related quality of life (HRQoL), specific symptoms, and prescribed antihistamine use.