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This study aimed to define clinical and virological parameters associated with spontaneous control of HIV replication in patients having initiated HAART during primary HIV infection, who underwent structured therapy interruption by two protocols with either fixed or HIV viremia‐guided scheme. At the end of the protocol all patients were changed to viremia‐guided scheme and observed for 12 months (follow‐up). Patients maintaining HIV viremia below the indications for resumption of HAART during the follow‐up, were defined controllers, those who had to resume HAART were defined non‐controllers. The following parameters were examined: pre‐interruption therapy duration, CD4+, HIV RNA, proviral DNA, evolution of viral quasispecies. No specific advantage was conferred by either interruption of structured therapy in the proportion of controllers and non‐controllers. Pre‐HAART and zenith CD4+, pre‐therapy interruption, HAART duration, but not pre‐HAART HIV RNA, were significantly higher in controllers as compared to non‐controllers. HIV RNA levels after the first interruption cycle of therapy were significantly lower in controllers than in non‐controllers. Proviral DNA levels were also lower in controllers at this time point. HIV RNA and proviral DNA levels associated with the last interruption of therapy cycle were not different from those associated with the first cycle, and, in spite of multiple waves of virus rebound, very few gag quasispecies variants emerged in each patient. The data suggest that pre‐treatment clinical parameters and virological events associated with the first viral rebound are crucial factors in determining the ability to control viral replication after multiple cycles of interruption of treatment. J. Med. Virol. 79: 1047–1054, 2007. © 2007 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

Semiconductor quantum dots (QDs) in planar germanium (Ge) heterostructures have emerged as front-runners for future hole-based quantum processors. Here, we present strong coupling between a hole charge qubit, defined in a double quantum dot (DQD) in planar Ge, and microwave photons in a high-impedance (Z r  = 1.3 kΩ) resonator based on an array of superconducting quantum interference devices (SQUIDs). Our investigation reveals vacuum-Rabi splittings with coupling strengths up to g 0 /2π = 260 MHz, and a cooperativity of C ~ 100, dependent on DQD tuning. Furthermore, utilizing the frequency tunability of our resonator, we explore the quenched energy splitting associated with strong Coulomb correlation effects in Ge QDs. The observed enhanced coherence of the strongly correlated excited state signals the presence of distinct symmetries within related spin functions, serving as a precursor to the strong coupling between photons and spin-charge hybrid qubits in planar Ge. This work paves the way towards coherent quantum connections between remote hole qubits in planar Ge, required to scale up hole-based quantum processors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Gate-tunable transmons (gatemons) employing semiconductor Josephson junctions have recently emerged as building blocks for hybrid quantum circuits. In this study, we present a gatemon fabricated in planar Germanium. We induce superconductivity in a two-dimensional hole gas by evaporating aluminum atop a thin spacer, which separates the superconductor from the Ge quantum well. The Josephson junction is then integrated into an Xmon circuit and capacitively coupled to a transmission line resonator. We showcase the qubit tunability in a broad frequency range with resonator and two-tone spectroscopy. Time-domain characterizations reveal energy relaxation and coherence times up to 75 ns. Our results, combined with the recent advances in the spin qubit field, pave the way towards novel hybrid and protected qubits in a group IV, CMOS-compatible material., (© 2024. The Author(s).)

In this work we theoretically investigate the possibility of observing strong coupling at mid-infrared frequencies within the group-IV semiconductor material platform. Our results show that the strong coupling condition is attainable in Ge/SiGe quantum wells integrated in hybrid metal-semiconductor microcavities, featuring a highly n-doped SiGe layer as one of the mirrors., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

This study reports the experimental demonstration of the first waveguide-integrated SiGe modulator using a PIN diode operating in a wide spectral range of the mid-infrared region. At the wavelength of 10 µm, an extinction ratio up to 10 dB is obtained in injection regime and 3.2 dB in depletion regime. High speed operation is obtained, up to 1.5 GHz. Furthermore, the device can also operate as an integrated photodetector. Photodetection has thus been characterized from 5.2 µm to 10 µm wavelengths showing an internal responsivity around 1 mA/W, and a 3 dB electro-optical bandwidth of 32 MHz. These results show a significant advancement in integrated photodetectors and electro-optical modulators for mid-infrared spectroscopy., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Superconductor/semiconductor hybrid devices have attracted increasing interest in the past years. Superconducting electronics aims to complement semiconductor technology, while hybrid architectures are at the forefront of new ideas such as topological superconductivity and protected qubits. In this work, we engineer the induced superconductivity in two-dimensional germanium hole gas by varying the distance between the quantum well and the aluminum. We demonstrate a hard superconducting gap and realize an electrically and flux tunable superconducting diode using a superconducting quantum interference device (SQUID). This allows to tune the current phase relation (CPR), to a regime where single Cooper pair tunneling is suppressed, creating a [Formula: see text] CPR. Shapiro experiments complement this interpretation and the microwave drive allows to create a diode with ≈ 100% efficiency. The reported results open up the path towards integration of spin qubit devices, microwave resonators and (protected) superconducting qubits on  the same silicon technology compatible platform., (© 2024. The Author(s).)

A promising alternative to bulk materials for the nonlinear coupling of optical fields is provided by photonic integrated circuits based on heterostructures made of asymmetric-coupled quantum wells. These devices achieve a huge nonlinear susceptivity but are affected by strong absorption. Here, driven by the technological relevance of the SiGe material system, we focus on Second-Harmonic Generation in the mid-infrared spectral region, realized by means of Ge-rich waveguides hosting p-type Ge/SiGe asymmetric coupled quantum wells. We present a theoretical investigation of the generation efficiency in terms of phase mismatch effects and trade-off between nonlinear coupling and absorption. To maximize the SHG efficiency at feasible propagation distances, we also individuate the optimal density of quantum wells. Our results indicate that conversion efficiencies of ≈ 0.6%/W can be achieved in WGs featuring lengths of few hundreds µm only.

Introduction: Inpatient Addiction Consultation Services (ACS) fill an important need by connecting hospitalized patients with substance use disorders with resources for treatment; however, providers of these services may be at risk for burnout. In this qualitative study, we aimed to identify factors associated with burnout and, conversely, resilience among multidisciplinary providers working on ACS., Methods: We completed 26 semi-structured interviews with clinicians working on ACS, including physicians, social workers, and advanced practice providers. Twelve institutions across the country were represented. The study recruited participants via email solicitation to ACS directors and then via snowball sampling. We used an inductive, grounded theory approach to analyze data., Results: Providers described factors contributing to burnout and strategies for promoting resilience, and three main themes arose: (1) Systemic barriers contributed to provider burnout, (2) Engaging in meaningful work increased resilience, and (3) Team dynamics influenced perceptions of burnout and resilience., Conclusion: Our results suggest that hospital-based addiction medicine work is intrinsically rewarding for many providers and that engaging with other addiction providers to debrief challenging encounters or engage in advocacy work can be protective against burnout. However, administrative and systemic factors are frequent sources of frustration for providers of ACS. Structured debriefings may help to mitigate burnout. Furthermore, training to enhance providers' ability to engage effectively in advocacy work within and between hospital systems has the potential to promote resilience and protect against burnout among ACS providers., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this work we theoretically investigate quantum confined Stark effect of intersubband transitions in asymmetric Ge/SiGe quantum wells for intensity modulation in the mid-infrared. Our calculations show that extinction ratios up to 1 dB and modulation speeds of several tens of GHz could be obtained in 100 µm long waveguides.

Background and Objectives: The opioid epidemic highlights the importance of evidence-based practices in the management of chronic pain and the need for improved resident education focused on chronic pain treatment and controlled substance use. We present the development, implementation, and outcomes of a novel, long-standing interprofessional safe prescribing committee (SPC) and resulting policy, protocol, and longitudinal curriculum to address patient care and educational gaps in chronic pain management for residents in training., Methods: The SPC developed and implemented an opioid prescribing policy, protocol, and longitudinal curriculum in a single, community-based residency program. We conducted a postcurriculum survey for resident graduates to assess impact of knowledge gained. We conducted a retrospective chart review for patients on chronic opioid therapy to assess change in morphine equivalent dosing (MED) and pain scores pre- and postintervention., Results: A postcurriculum survey was completed by 20/26 (77%) graduates; 18/20 (90%) felt well-equipped to manage chronic pain based on their residency training experience. We completed a retrospective chart review on 57 patients. We found a significant decrease in MED (-20.34 [SE 5.12], P<.0001) at intervention visit with MED reductions maintained through the postintervention period (-9.43 per year additional decrease [SE 5.25], P=.073). We observed improvement in postintervention pain scores (P=.017)., Conclusions: Our study illustrates the effectiveness of an interprofessional committee in lowering prescribed opioid doses and enhancing chronic pain education in a community-based residency setting.

Sea drowning is a common cause of accidental death worldwide. Respiratory complications such as acute pulmonary oedema, which is often complicated by acute respiratory distress syndrome, is often seen. Noninvasive ventilation is already widely used as a first approach to treat acute respiratory failure resulting from multiple diseases. We report a case of a 45 year old man with a history of epilepsy, motor and mental handicap who developed acute respiratory failure secondary to sea water drowning after an epileptic crisis. We illustrate successful and rapid management of this case with noninvasive ventilation. We emphasize the advantages and limitations of using noninvasive ventilation to treat acute respiratory failure due to sea water drowning syndrome.

Ehlers-Danlos syndrome, characterized by hyperextensible skin, hypermobile joints, and fragile vessels, is the most common heritable disorder of connective tissue and has an estimated prevalence of 1 in 5000. Pulmonary involvement with signs of lung destruction (bullous emphysema) as first presentation is unusual. We report a case of monozygotic twins 37 years old men with occasional evidence of bullous emphysema with previously undiagnosed Ehlers-Danlos syndrome type IV. We emphasize the importance of considering uncommon genetic causes of emphysema in young adults, discuss underlining pathophysiological mechanisms and propose a conservative management and follow-up.

Background: Pharmaceutical opioid related deaths have increased. This study aimed to place pharmaceutical opioid overdose deaths within the context of heroin, cocaine, psychostimulants, and pharmaceutical sedative hypnotics examine demographic trends, and describe common combinations of substances involved in opioid related deaths., Methods: We reviewed deaths among 15-64 year olds in the US from 1999-2009 using death certificate data available through the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) Database. We identified International Classification of Disease-10 codes describing accidental overdose deaths, including poisonings related to stimulants, pharmaceutical drugs, and heroin. We used crude and age adjusted death rates (deaths/100,000 person years [p-y] and 95% confidence interval [CI] and multivariable Poisson regression models, yielding incident rate ratios; IRRs), for analysis., Results: The age adjusted death rate related to pharmaceutical opioids increased almost 4-fold from 1999 to 2009 (1.54/100,000 p-y [95% CI 1.49-1.60] to 6.05/100,000 p-y [95% CI 5.95-6.16; p<0.001). From 1999 to 2009, pharmaceutical opioids were responsible for the highest relative increase in overdose death rates (IRR 4.22, 95% CI 3.03-5.87) followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90). Heroin related overdose death rates increased from 2007 to 2009 (1.05/100,000 persons [95% CI 1.00-1.09] to 1.43/100,000 persons [95% CI 1.38-1.48; p<0.001). From 2005-2009 the combination of pharmaceutical opioids and benzodiazepines was the most common cause of polysubstance overdose deaths (1.27/100,000 p-y (95% CI 1.25-1.30)., Conclusion: Strategies, such as wider implementation of naloxone, expanded access to treatment, and development of new interventions are needed to curb the pharmaceutical opioid overdose epidemic., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Increased methamphetamine use occurred during the last decade and little is known about factors associated with death. This study assesses trends in psychostimulant deaths in the United States., Methods: Using the Centers for Disease Control and Prevention (CDC) Wonder Database, the authors searched deaths among 15- to 64-year-olds from 1999 to 2009 for decedents who died with "psychostimulants with abuse potential, excluding cocaine." The International Classification of Diseases (ICD) code T43.6 was used to identify methamphetamine-related deaths. Trends in death rates and the most common underlying causes of death were determined. For recent trends, age-adjusted death rates/100,000 person-years (p-y) and (95% confidence intervals [CIs]) among those who died with psychostimulants were calculated., Results: The rate of psychostimulant-related deaths increased 3-fold from 1999 (0.37/100,000 p-y; 95% CI: 0.354-0.39) to 2005 (1.05/100,000 p-y; 95% CI: 1.01-1.10). Deaths steadily declined from 2006 to 2008, but rose again in 2009 to 0.97/100,000 p-y (95% CI: 0.92-1.01). Across all age groups, men had a 2 to 3 times higher rate of death than women. American Indians/Alaska Natives were twice as likely to die a psychostimulant-related death as compared with non-Hispanic whites. The northwestern/western region of the US had the highest rates of psychostimulant-related deaths, whereas the northeastern region had the lowest death rates. "Accidental poisonings" (ICD-10: X40-49) was the most frequently listed cause of death among those who died with psychostimulants., Conclusions: Psychostimulant-related deaths increased from 1999 to 2006, declined from 2006 to 2008, but rebounded in 2009. Interventions targeting those at highest risk of death must be implemented and studied to prevent increasing deaths.

Objectives: Psychostimulants are highly addictive and their use is increasing. Little is known about psychostimulant-related deaths. This study identified characteristics, risk factors, and contributing substances reported upon death among former prison inmates who died from a psychostimulant-related death., Methods: This retrospective cohort study of released inmates from 1999 to 2003 (N = 30,237) linked data from the Washington State Department of Corrections with the National Death Index. We examined characteristics of individuals who died with psychostimulants listed among their causes of death. These were categorized into 3 groups: (1) noncocaine psychostimulants, (2) cocaine only, and (3) all psychostimulants. Cox proportional hazards regression determined risk factors for death in each group, and the risk of death in the first 2 weeks after release from prison, Results: Of the 443 inmates who died, 25 (6%) had noncocaine psychostimulants listed among their causes of death. Six of these 25 deaths had both noncocaine psychostimulants and cocaine listed among their causes-of-death. Most of the former inmates who died with noncocaine psychostimulants were male (n = 21, 84%) and non-Hispanic white (88%, n = 22). Cocaine only was listed among the causes-of-death for 49 former inmates; most were male (n = 35, 71%) and non-Hispanic white (n = 27, 55%). Longer length of incarceration was associated with a reduced risk of death from any psychostimulant use (hazard ratio = 0.76, confidence interval = 0.63-0.920 for each additional year of incarceration) and from use of noncocaine psychostimulants (hazard ratio = 0.42, 95% CI = 0.22-0.80). Risk of death was highest during the first 2 weeks postrelease for cocaine only-related deaths (incidence mortality ratio = 1224.0, confidence interval = 583-1865)., Conclusions: Former prisoners have a significant risk of death from psychostimulants, especially within the first 2 weeks postrelease.

The most reliable predictor of treatment efficacy in hepatitis C is HCV viremia decay at week 12 [early virological response (EVR)]. We investigated whether the ability of peripheral blood mononuclear cells (PBMC) to mount an interferon (IFN) response in vitro could be predictive of EVR. Fifteen patients treated with PEG IFNalpha + RBV, with pre-therapy frozen PBMC, were retrospectively selected. After a 3 hr PBMC exposure to IFNalpha in vitro, up-regulation of mRNA for IFN-stimulated genes (ISG) was measured by membrane super-array. ISG mRNA levels in unstimulated PBMC were low, but beta2M and CASP1 were significantly higher in EVR vs non-EVR. ISG mRNA up-regulation by IFN was more pronounced in EVR vs non-EVR. For 7 genes (IP-10, IFIT1, IFIT2, IFIT3, TRAIL, KIAA1628 and OAS2) cut-off levels were established, by ROC analysis, able to correctly classify all EVR and non-EVR. Early virological response to PEG IFNalpha +RBV is correlated with the pre-therapy ability of PBMC to activate an IFN response in vitro. If validated in a wider cohort of patients, the ability of this set of ISG to discriminate between EVR and non-EVR may be useful for pre-therapy evaluation, particularly in patients with unfavourable combinations of conventional response predictors.

Background: We estimated the prevalence of hepatitis C virus (HCV) in cervical cytobrush samples from HCV/human immunodeficiency virus (HIV)-coinfected women and analyzed the HCV quasi species in both cytobrush and plasma samples. Possible compartmentalization of viral quasi species in the genital tract and plasma was evaluated by comparison of genetic heterogeneity and use of phylogenetic analysis., Methods: Paired plasma and cytobrush samples were obtained from 85 HCV/HIV-coinfected women. The presence of HCV in cytobrush samples was evaluated by reverse-transcription polymerase chain reaction of the 5' untranslated region. Viral quasi species were analyzed by cloning and sequencing the highly variable region-1 in 8 patients., Results: HCV was detected in 27% of cytobrush samples. The composition of viral quasi species was different in the 2 body compartments at both the nucleotide and amino acid level. In fact, the mean complexity was significantly lower in cytobrush samples, and a similar trend was observed for the other parameters of heterogeneity. Phylogenetic analysis and amino acid alignment identified several viral variants that were unique to each body compartment., Conclusions: Our data suggest that the genital and plasma quasi species represent distinct subpopulations, which possibly reflects compartmentalized viral replication. Alternatively, cell carriers harboring viral quasi species in the genital tract that are distinct from those in plasma could transfer the virus through the barrier separating the 2 body sites.

Vero cells transfected with either neo- or bcl-2-plasmid were infected with SARS-CoV at a high multiplicity of infection. Apoptosis appeared after the onset of CPE and completion of virus replication, and could be prevented by Bcl-2 expression. Apoptosis is likely mediated by the mitochondrial pathway, as demonstrated by its inhibition using Bcl-2, and by the activation of the caspase cascade, resulting in PARP cleavage. Prevention of apoptosis did not affect susceptibility to infection, kinetics and extent of viral replication and release, thus implying that apoptosis is not involved in facilitating release and/or dissemination of SARS-CoV in Vero cells.

We used a molecular panel, targeting seven enteric viruses, to explore the advantage of using molecular methods to establish the etiology of enteric diseases and to evaluate the prevalence of enteric viruses in asymptomatic human immunodeficiency virus-infected patients. This approach favors rapidity and sensitivity of laboratory diagnosis of viral enteric syndromes.