TB preventive therapy preferences among children and adolescents.

BACKGROUND: TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers.METHODS: We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis.RESULTS: Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits.CONCLUSIONS: Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.

Hierarchical autoclassification of cryo-EM samples and macromolecular energy landscape determination.

BACKGROUND AND OBJECTIVE: Cryo-electron microscopy using single particle analysis is a powerful technique for obtaining 3D reconstructions of macromolecules in near native conditions. One of its major advances is its capacity to reveal conformations of dynamic molecular complexes. Most popular and successful current approaches to analyzing heterogeneous complexes are founded on Bayesian inference. However, these 3D classification methods require the tuning of specific parameters by the user and the use of complicated 3D re-classification procedures for samples affected by extensive heterogeneity. Thus, the success of these approaches highly depends on the user experience. We introduce a robust approach to identify many different conformations presented in a cryo-EM dataset based on Bayesian inference through Relion classification methods that does not require tuning of parameters and reclassification strategies. METHODS: The algorithm allows both 2D and 3D classification and is based on a hierarchical clustering approach that runs automatically without requiring typical inputs, such as the number of conformations present in the dataset or the required classification iterations. This approach is applied to robustly determine the energy landscapes of macromolecules. RESULTS: We tested the performance of the methods proposed here using four different datasets, comprising structurally homogeneous and highly heterogeneous cases. In all cases, the approach provided excellent results. The routines are publicly available as part of the CryoMethods plugin included in the Scipion package. CONCLUSIONS: Our results show that the proposed method can be used to align and classify homogeneous and heterogeneous datasets without requiring previous alignment information or any prior knowledge about the number of co-existing conformations. The approach can be used for both 2D and 3D autoclassification and only requires an initial volume. In addition, the approach is robust to the "attractor" problem providing many different conformations/views for samples affected by extensive heterogeneity. The obtained 3D classes can render high resolution 3D structures, while the obtained energy landscapes can be used to determine structural trajectories.

[The hypertensive emergency situation : Recommendations for initial drug therapy management]. / Der hypertensive Notfall : Empfehlungen zum initialen medikamentösen Therapiemanagement.

The hypertensive emergency situation is characterized by an acute-mostly life-threatening-blood pressure derailment with the risk of acute end organ damage. It is an acute manifestation of arterial hypertension, which manifests in a variety of symptoms. The etiology is in most cases long-term (chronic) hypertension as a result of low compliance or inadequate antihypertensive therapy. It can also occur as a first manifestation of arterial hypertension. It requires timely antihypertensive drug therapy, which should be initiated in an intensive or intermediate care unit. The choice of antihypertensive therapy regimen should be based on the underlying end organ damage. Fast-acting, easily controllable and intravenously administered substances should be preferred. The most commonly used substances (groups) are urapidil, nitroglycerin, beta blockers and short-acting calcium channel blockers. With a few exceptions, a deliberate, rapid reduction in blood pressure of no more than 20-25% of the initial value is sufficient for extracerebral causes. A subsequent systolic blood pressure target of 160/100 mm Hg should be aimed for within the next 2-6 h. An overly rapid drop in blood pressure can lead to reduced blood flow to the central nervous system due to changes in autoregulation. Exceptions to this rule are acute aortic dissection and flash pulmonary edema-in these cases, prompt blood pressure normalization should be achieved. The initial acute therapy should be followed by a more detailed investigation of the cause and a long-term therapy setting based on this.

Mental health over nine months during the SARS-CoV2 pandemic: Representative cross-sectional survey in twelve waves between April and December 2020 in Austria.

BACKGROUND: There is accumulating evidence about detrimental impacts of the pandemic on population mental health, but knowledge on risk of groups specifically affected by the pandemic and variations across time is still limited. METHODS: We surveyed approximately n=1,000 Austrian residents in 12 waves between April and December 2020 (n=12,029). Outcomes were suicidal ideation (Beck Suicidal Ideation Scale), depressive symptoms (Patient Health Questionnaire-9), anxiety (Hospital Anxiety Depression Scale), and domestic violence. We also assessed the perceived burden from the pandemic. Demographic and Covid-19 specific occupational and morbidity-related variables were used to explain outcomes in multivariable regression analyses, controlling for well-established risk factors of mental ill-health, and variations over time were analyzed. RESULTS: Young age, working in healthcare or from home, and own Covid-19 illness were consistent risk factors controlling for a wide range of known mental health risk factors. Time patterns in the perceived burden from Covid-19-related measures were consistent with the time sequence of restrictions and relaxations of governmental measures. Depressive and anxiety symptoms were relatively stable over time, with some increase of depression during the second phase of lockdowns. Domestic violence increased immediately after both hard lockdowns. Suicidal ideation decreased slightly over time, with a low during the second hard lockdown. Mental health indicators for women and young people showed some deterioration over time, whereas those reporting own Covid-19 illness improved. LIMITATIONS: Data from before the pandemic were not available. CONCLUSIONS: Among mental health outcomes, increases in domestic violence and, to some smaller extent, depressive symptoms, appeared most closely related to the timing of hard lockdowns. Healthcare staff, individuals working from home, those with Covid-19, as well as young people and women are non-traditional risk groups who warrant heightened attention in prevention during and in the aftermath of the pandemic.

Impact of bodyweight-adjusted antimicrobial prophylaxis on surgical-site infection rates.

BACKGROUND: Antimicrobial prophylaxis (AMP) adjustment according to bodyweight to prevent surgical-site infections (SSI) is controversial. The impact of weight-adjusted AMP dosing on SSI rates was investigated here. METHODS: Results from a first study of patients undergoing visceral, vascular or trauma operations, and receiving standard AMP, enabled retrospective evaluation of the impact of bodyweight and BMI on SSI rates, and identification of patients eligible for weight-adjusted AMP. In a subsequent observational prospective study, patients weighing at least 80 kg were assigned to receive double-dose AMP. Risk factors for SSI, including ASA classification, duration and type of surgery, wound class, diabetes, weight in kilograms, BMI, age, and AMP dose, were evaluated in multivariable analysis. RESULTS: In the first study (3508 patients), bodyweight and BMI significantly correlated with higher rates of all SSI subclasses (both P < 0.001). An 80-kg cut-off identified patients receiving single-dose AMP who were at higher risk of SSI. In the prospective study (2161 patients), 546 patients weighing 80 kg or more who received only single-dose AMP had higher rates of all SSI types than a group of 1615 who received double-dose AMP (odds ratio (OR) 4.40, 95 per cent c.i. 3.18 to 6.23; P < 0.001). In multivariable analysis including 5021 patients from both cohorts, bodyweight (OR 1.01, 1.00 to 1.02; P = 0.008), BMI (OR 1.01, 1.00 to 1.02; P = 0.007) and double-dose AMP (OR 0.33, 0.23 to 0.46; P < 0.001) among other variables were independently associated with SSI rates. CONCLUSION: Double-dose AMP decreases SSI rates in patients weighing 80 kg or more.

Low-dose (S)TEM elemental analysis of water and oxygen uptake in beam sensitive materials.

The performance stability of organic photovoltaics (OPVs) is largely determined by their nanoscale morphology and composition and is highly dependent on the interaction with oxygen and water from air. Low-dose cryo-(S)TEM techniques, in combination with OPV donor-acceptor model systems, can be used to assess oxygen- and water-uptake in the donor, acceptor and their interface. By determining a materials dependent critical electron dose from the decay of the oxygen K-edge intensity in Electron Energy Loss Spectra, we reliably measured oxygen- and water-uptake minimizing and correcting electron beam effects. With measurements below the dose limit the capability of STEM-EDX, EFTEM and STEM-EELS techniques are compared to qualitatively and quantitatively measure oxygen and water uptake in these OPV model systems. Here we demonstrate that oxygen and water is mainly taken up in acceptor-rich regions, and that specific oxygen uptake at the donor-acceptor interphase does not occur. STEM-EELS is shown to be the best suitable technique, enabling quantification of the local oxygen concentration in OPV model systems.

Hypothalamus enlargement in mood disorders.

OBJECTIVE: The purpose of this study was to determine, in vivo, whether the hypothalamus volume is reduced in patients with mood disorders. METHODS: The cross-sectional study included 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 patients with bipolar disorder, and 23 controls. Twenty of the controls were matched to the MDDu. Seven Tesla, T1-weighted magnetic resonance images were acquired and processed using methods specifically developed for high-precision volumetry of the hypothalamus. RESULTS: An overall group difference was observed for the left hypothalamus volume corrected for intracranial volume. Planned contrasts identified that the left hypothalamus was approximately 5% larger in each patient group compared with the control group. A paired t-test with the 20 matched pairs of MDDu and controls and without correction for covariates confirmed the larger left hypothalamus volume in MDDu. CONCLUSIONS: Contrary to our expectations, the hypothalamus volume was increased in patients with uni- and bipolar affective disorders. The effect was left-sided and independent of medication status or statistical correction for covariates. Supported by emerging evidence that the stress response may be related to structural and functional asymmetry in the brain, our finding suggests a crucial role of the hypothalamus in mood disorders.

Predicting suicidal ideation by interpersonal variables, hopelessness and depression in real-time. An ecological momentary assessment study in psychiatric inpatients with depression.

OBJECTIVE: To extend evidence on the short-term variability of passive and active suicidal ideation (SI) and the association with suggested proximal risk factors such as interpersonal variables (perceived burdensomeness [PB], thwarted belongingness [TB], hopelessness, and depression) in real-time. METHODS: This is an observational study using a prospective design applying ecological momentary assessments (EMA). Eligible for study inclusion were inpatients with unipolar depression, current or lifetime suicidal ideation, and fluent German. Over six days, 74 participants rated their momentary level of passive and active SI, PB, TB, depressiveness, and hopelessness up to 10 times per day on smartphones. Data was collected from August 2015 to July 2017. Compliance was excellent (89.7%). RESULTS: Mean squared successive differences supported temporal instability for all variables. According intra-class correlations, between 25% and 47% of variance was accounted for by within-person variability. Multilevel analysis demonstrated significant positive associations between hopelessness, depressiveness, PB, and TB with passive SI. Prospectively, hopelessness and PB remained predictors of passive SI. For active SI, hopelessness, depression, PB, and TB were significantly associated cross-sectionally. Prospectively, hopelessness, PB, and the interaction PBxTB predicted active SI. All models were controlled for previous level of SI. CONCLUSIONS: This study provides further evidence on the short-term variability of SI in very short time frames implying the need of assessing SI repeatedly in clinical and research settings. The associations between interpersonal variables and passive and active SI were only partial in line with assumptions of the Interpersonal Theory of Suicide. Overall, the effects were small warranting further investigation.

[Pacemaker and MRI in clinical practice]. / Herzschrittmacher und MRT im klinischen Alltag.

The number of cardiac pacemaker wearers is continuously increasing in Germany as well as worldwide. The probability of indications for a magnetic resonance imaging (MRI) examination during the lifetime is approximately 50-75% for every person. An MRI examination is nowadays possible for pacemaker wearers under certain conditions. Due to the technical developments during the last 10 years certain MRI-conditional pacemakers are available. The recommendations of the German and American medical specialist societies currently allow an MRI examination in patients with conventional pacemakers beyond the approval conditions (off-label use) under prespecified conditions, based on the study data. This article summarizes the information on conditions of use and reprogramming strategies as well as on the study situation for the clinical routine.

Adverse obstetric history is not a risk factor for poor outcome after ventral rectopexy for obstructive defaecation syndrome.

AIM: Ventral rectopexy (VR) has gained popularity in the management of obstructive defaecation syndrome (ODS) due to a symptomatic rectocele ± intussusception. Data on the efficacy and safety of VR are variable and there are few predictors of successful outcome. This study aimed to examine whether or not an adverse obstetric history influenced the functional outcome following VR for ODS. METHOD: This was a retrospective study of a cohort of 76 consecutive patients who had undergone VR for ODS at a tertiary referral centre between 2012 and 2015. Patients were followed up by telephone questionnaire. The obstetric history and pre- and postoperative symptoms of ODS and faecal incontinence (FI) were obtained from telephone interviews. RESULTS: In this cohort, symptoms of ODS were significantly improved by surgery, with 56% of patients showing a reduction of symptoms of 50% or more (P < 0.001). Subgroup analysis demonstrated that a lower body mass index (BMI; 24.4 vs 27.3 kg/m2 ; P < 0.05) and shorter duration of symptoms (7 vs 10 years; P < 0.05) led to a better outcome. VR had no effect on FI. Obstetric factors such as foetal weight, instrumental delivery, episiotomy, perineal tear and total number of deliveries did not influence outcomes. CONCLUSION: Patients with a less straightforward obstetric history can be reassured that this should not adversely influence the functional outcome after VR for ODS. Colorectal surgeons who offer this surgery should warn patients with an elevated BMI or with longstanding symptoms that the operation may be less successful than for those with a lower BMI or shorter duration of symptoms.

[Attention deficit-hyperactivity disorder (ADHD) and comorbid mental disorders : ADHD-specific self-rating scales in differential diagnostics]. / Aufmerksamkeitsdefizit­/Hyperaktivitätssyndrom (ADHS) und komorbide psychische Erkrankungen : ADHS-spezifische Selbstbeurteilungsskalen bei der Differenzialdiagnostik.

BACKGROUND: It is still unclear how well the established attention deficit-hyperactive disorder (ADHD)-specific rating scales can differentiate between ADHD symptoms and symptoms of other mental disorders. METHODS: A total of 274 patients with suspected adult ADHD were extensively examined clinically and guideline-conform in an ADHD outpatient clinic. In 190 patients the diagnosis of ADHD could be made with certainty. The patients were also subsequently assessed according to the DSM IV criteria by self-rating scales on current (ADHS-SB, ASRS, CAARS) and retrospective (WURS-K) complaints. A binary logistic regression analysis was performed in order to extract from the questionnaires, which could best distinguish the diagnosis of ADHD from other mental disorders. RESULTS: The results showed that two self-rating scales (WURS-K and ADHS-SB) were sufficient to correctly diagnose ADHD in 83% of the patients examined with a sensitivity of 94% and specificity of 56%. CONCLUSION: The ADHD-specific self-rating scales are additionally useful for the diagnostic differentiation between ADHD-specific and other psychiatric symptoms in the clinical practice and can improve the safety of the diagnosis.

Rapidly star-forming galaxies adjacent to quasars at redshifts exceeding 6.

The existence of massive (1011 solar masses) elliptical galaxies by redshift z ≈ 4 (refs 1, 2, 3; when the Universe was 1.5 billion years old) necessitates the presence of galaxies with star-formation rates exceeding 100 solar masses per year at z > 6 (corresponding to an age of the Universe of less than 1 billion years). Surveys have discovered hundreds of galaxies at these early cosmic epochs, but their star-formation rates are more than an order of magnitude lower. The only known galaxies with very high star-formation rates at z > 6 are, with one exception, the host galaxies of quasars, but these galaxies also host accreting supermassive (more than 109 solar masses) black holes, which probably affect the properties of the galaxies. Here we report observations of an emission line of singly ionized carbon ([C ii] at a wavelength of 158 micrometres) in four galaxies at z > 6 that are companions of quasars, with velocity offsets of less than 600 kilometres per second and linear offsets of less than 100 kiloparsecs. The discovery of these four galaxies was serendipitous; they are close to their companion quasars and appear bright in the far-infrared. On the basis of the [C ii] measurements, we estimate star-formation rates in the companions of more than 100 solar masses per year. These sources are similar to the host galaxies of the quasars in [C ii] brightness, linewidth and implied dynamical mass, but do not show evidence for accreting supermassive black holes. Similar systems have previously been found at lower redshift. We find such close companions in four out of the twenty-five z > 6 quasars surveyed, a fraction that needs to be accounted for in simulations. If they are representative of the bright end of the [C ii] luminosity function, then they can account for the population of massive elliptical galaxies at z ≈ 4 in terms of the density of cosmic space.

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

Physical activity, cardiorespiratory fitness and carotid intima thickness: sedentary occupation as risk factor for atherosclerosis and obesity.

OBJECTIVE: The influence of occupational physical activity on markers of atherosclerosis, prevalence of metabolic syndrome and physical performance has been understudied in current literature. Main aim of this study was to examine the association between physical work environment and physiological performance measures, physical activity, metabolic parameters and carotid atherosclerosis among German career firefighters and sedentary clerks. PATIENTS AND METHODS: We prospectively examined and recruited 143 male German civil servants (97 firefighters [FFs], and 46 sedentary clerks [SCs]). Correlation for each parameter for the groups were compared using a linear regression model adjusted for age. RESULTS: 97 firefighters (FFs) showed higher maximal aerobic power (VO2max) of 3.17 ± 0.44 L/min compared to 46 sedentary clerks (SCs) 2.85 ± 0.52 L/min (-0.21 CI -0.39-0.04, p = 0.018). Physical activity (PA, in METS/week) in FFs was 3953 ± 2688 and in SC 2212 ± 2293 (-1791.86 CI -2650--934, p = 0.000). Body fat was 17.7 ± 6.2% in FFs and in SCs 20.8 ± 6.5% (1.98 CI -0.28-4.25, p = 0.086). Waist circumference was 89.8 ± 10.0 cm in FFs and in SCs 97.3 ± 11.7 (-4.89 CI 1.24-8.55, p = 0.009). Carotid intima media thickness (IMT) showed significant difference for the left carotid artery 0.69 ± 0.19 mm in FFs vs. SCs 0.81 ± 0.20 (0.07 CI 0.01-0.14, p = 0.030). Metabolic syndrome was found in 12 out of 98 FFs (13.4%), and in 14 out of 46 SCs (30.43%). CONCLUSIONS: FFs showed significantly higher physical activity levels compared with the SCs. SCs had higher cardiovascular risk profile, higher prevalence of metabolic syndrome, higher waist circumference and significantly higher IMT than FFs. In conclusion, sedentary occupations have higher cardiovascular risk secondary to accelerated atherosclerosis.

A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers

BACKGROUND: The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. METHODS: The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acute post-operative wound vs. non-healing wound of 30 or more days). Major amputation and incomplete healing were selected as critical outcomes of interest. RESULTS: This analysis showed that HBO2 is beneficial in preventing amputation and promoting complete healing in patients with Wagner Grade 3 or greater DFUs who have just undergone surgical debridement of the foot as well as in patients with Wagner Grade 3 or greater DFUs that have shown no significant improvement after 30 or more days of treatment. In patients with Wagner Grade 2 or lower DFUs, there was inadequate evidence to justify the use of HBO2 as an adjunctive treatment. CONCLUSIONS: Clinicians, patients, and policy-makers should engage in shared decision-making and consider HBO2 as an adjunctive treatment of DFUs that fit the criteria outlined in this guideline. The current body of evidence provides a moderate level of evidence supporting the use of HBO2 for DFUs. Future research should be directed at improving methods for patient selection, testing various treatment protocols and improving our confidence in the existing estimates.(AU)

Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord.

Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus. Viral particles were packaged containing a green fluorescent protein reporter construct under the control of the phosphoglycerokinase promoter. Both vectors produced high-titer particles with successful integration of the glycoproteins into the particle envelope and significant transduction of neurons in vitro. Injection of the SADB19 chimeric viral vector into the lumbar spinal cord of adult mice mediated a strong preference for gene transfer to local neurons and axonal terminals, with retrograde transport to neurons in the brainstem, hypothalamus and cerebral cortex. Development of this vector provides a useful means to reliably target select populations of neurons by retrograde targeting.

[Assertive community treatment in patients with severe obsessive-compulsive disorders]. / Aufsuchende gemeindepsychiatrische Behandlung bei Patienten mit schweren Zwangsstörungen.

For the use of psychosocial treatments for severe mental illness, there is a high evidence level. Obsessive-compulsive disorders are accompanied by severe disabilities in one third of the cases, however, there is little scientific research on the use of psychosocial therapies in patients with obsessive-compulsive disorders. In the following, the concept of an outreaching multi-professional treatment based on the assertive community treatment (ACT) method for severe compulsive illnesses is presented and discussed based on two case studies. There was an obvious reduction in clinically rated severity of obsessive-compulsive disorder symptoms, as measured by the Yale-Brown obsessive-compulsive scale (Y-BOCS), over the course of ACT. Comparison between pre- and post-treatment states demonstrated a reduction in the total Y-BOCS score after the treatment (case 1: total Y-BOCS score 37 versus 26; case 2: total Y-BOCS score 36 versus 16).

Discontinuation of clozapine: a 15-year naturalistic retrospective study of 320 patients.

OBJECTIVE: Clozapine is underutilized in the management of treatment-resistant schizophrenia. To understand contributing factors, we analyzed the frequency and causes of clozapine discontinuations that occurred over a 15-year period in a clinical setting. METHOD: Data were extracted from computerized records and from mandatory termination reports for discontinuation events 1993-2007. The reasons for termination were analyzed. RESULTS: Over half of the patients (n = 183/320; 57%) had at least one discontinuation (median time 609 days). The two most common causes for discontinuation were non-adherence (35%) and side-effects (28%). Hematological side-effects accounted for 45% of all side-effect associated discontinuations; most such patients remained eligible for clozapine treatment, and a significant fraction remained on clozapine after rechallenge. Central nervous system side-effects accounted for 35% of side-effect induced discontinuations. General factors significantly associated with discontinuation were African American race, older age at initiation of clozapine and less improvement in psychiatric symptoms. CONCLUSION: In addition to anticipating and addressing causes of non-adherence, psychiatrists should consider clozapine rechallenge in eligible patients and implement measures to mitigate clozapine-associated sedation, seizures, and other side-effects. Future studies should particularly address why African American and older patients may be more likely to discontinue clozapine.

Microcavity controlled coupling of excitonic qubits.

Controlled non-local energy and coherence transfer enables light harvesting in photosynthesis and non-local logical operations in quantum computing. This process is intuitively pictured by a pair of mechanical oscillators, coupled by a spring, allowing for a reversible exchange of excitation. On a microscopic level, the most relevant mechanism of coherent coupling of distant quantum bits--like trapped ions, superconducting qubits or excitons confined in semiconductor quantum dots--is coupling via the electromagnetic field. Here we demonstrate the controlled coherent coupling of spatially separated quantum dots via the photon mode of a solid state microresonator using the strong exciton-photon coupling regime. This is enabled by two-dimensional spectroscopy of the sample's coherent response, a sensitive probe of the coherent coupling. The results are quantitatively understood in a rigorous description of the cavity-mediated coupling of the quantum dot excitons. This mechanism can be used, for instance in photonic crystal cavity networks, to enable a long-range, non-local coherent coupling.