Evaluating individualized treatment effect predictions: A model-based perspective on discrimination and calibration assessment.

In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their performance. In this paper, we aim to facilitate the validation of prediction models for individualized treatment effects. The estimands of interest are defined based on the potential outcomes framework, which facilitates a comparison of existing and novel measures. In particular, we examine existing measures of discrimination for benefit (variations of the c-for-benefit), and propose model-based extensions to the treatment effect setting for discrimination and calibration metrics that have a strong basis in outcome risk prediction. The main focus is on randomized trial data with binary endpoints and on models that provide individualized treatment effect predictions and potential outcome predictions. We use simulated data to provide insight into the characteristics of the examined discrimination and calibration statistics under consideration, and further illustrate all methods in a trial of acute ischemic stroke treatment. The results show that the proposed model-based statistics had the best characteristics in terms of bias and accuracy. While resampling methods adjusted for the optimism of performance estimates in the development data, they had a high variance across replications that limited their accuracy. Therefore, individualized treatment effect models are best validated in independent data. To aid implementation, a software implementation of the proposed methods was made available in R.

[Bilateral vestibulopathy and sensorineural hearing loss in necrobiotic xanthogranuloma, multiple myeloma and amiloidosis]. / Dvustoronnyaya vestibulopatiya i sensonevral'naya tugoukhost' u patsienta s nekroticheskoi ksantogranulemoi, mnozhestvennoi mielomoi i amiloidozom.

This article describes a rare case of necrotic xanthogranuloma in a 46-year-old patient who presented with the development of periorbital xanthelasms, progressive bilateral sensorineural hearing loss and bilateral vestibulopathy, followed by multiple myeloma and amyloidosis. For several years, the patient underwent standard rehabilitation for chronic sensorineural hearing loss and was fitted with a hearing aid. During hospitalisation for exacerbation of chronic bronchitis, monoclonal gammopathy was identified, and later, after careful examination and repeated biopsies, necrotic xanthogranuloma, multiple myeloma and AL-amyloidosis were confirmed. Targeted immunochemotherapy resulted in improvement of hearing and significant recovery of the vestibuloocular reflex bilaterally.

Associations between psychosocial work environment factors and first-time and recurrent treatment for depression: a prospective cohort study of 24,226 employees.

AIMS: Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression. METHODS: The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort-reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding. RESULTS: Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30-2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97-1.66) and job strain (OR = 1.24, 95% CI: 0.97-1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04-1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03-1.67) and low job control (OR = 1.27, 95% CI: 1.00-1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations. CONCLUSIONS: Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Real-time robot topological localization and mapping with limited visual sampling in simulated buried pipe networks.

Introduction: Our work introduces a real-time robotic localization and mapping system for buried pipe networks. Methods: The system integrates non-vision-based exploration and navigation with an active-vision-based localization and topological mapping algorithm. This algorithm is selectively activated at topologically key locations, such as junctions. Non-vision-based sensors are employed to detect junctions, minimizing the use of visual data and limiting the number of images taken within junctions. Results: The primary aim is to provide an accurate and efficient mapping of the pipe network while ensuring real-time performance and reduced computational requirements. Discussion: Simulation results featuring robots with fully autonomous control in a virtual pipe network environment are presented. These simulations effectively demonstrate the feasibility of our approach in principle, offering a practical solution for mapping and localization in buried pipes.

The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: An application to the PROSPER randomised controlled trial.

BACKGROUND & AIMS: Clinical guidelines often recommend to treat individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness. METHODS: We reanalysed the PROSPER randomised controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared to placebo (n= 2913): (i) pravastatin (n= 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n= 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n= 2890). RESULTS: We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response. CONCLUSIONS: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.

This study invistigates whether an algorithm to predict how much old age individuals would benefit from a statin treatment could be useful to guide clinicians in their prescription decision-making; the key findings are: About one out of seven individuals included in the study has no predicted benefit of pravastatin; Compared to prescribing pravastatin to all old age individuals at risk of cardiovascular diseases, withholding pravastatin in those with no predicted benefit seems to lead to a better prevention of cardiovascular events.

Phonon Laser in the Quantum Regime.

We demonstrate a trapped-ion system with two competing dissipation channels, implemented independently on two ion species cotrapped in a Paul trap. By controlling coherent spin-oscillator couplings and optical pumping rates we explore the phase diagram of this system, which exhibits a regime analogous to that of a (phonon) laser but operates close to the quantum ground state with an average phonon number of n[over ¯]<10. We demonstrate phase locking of the oscillator to an additional resonant drive, and also observe the phase diffusion of the resulting state under dissipation by reconstructing the quantum state from a measurement of the characteristic function.

Autonomous control for miniaturized mobile robots in unknown pipe networks.

Despite recent advances in robotic technology, sewer pipe inspection is still limited to conventional approaches that use cable-tethered robots. Such commercially available tethered robots lack autonomy, and their operation must be manually controlled via their tethered cables. Consequently, they can only travel to a certain distance in pipe, cannot access small-diameter pipes, and their deployment incurs high costs for highly skilled operators. In this paper, we introduce a miniaturised mobile robot for pipe inspection. We present an autonomous control strategy for this robot that is effective, stable, and requires only low-computational resources. The robots used here can access pipes as small as 75 mm in diameter. Due to their small size, low carrying capacity, and limited battery supply, our robots can only carry simple sensors, a small processor, and miniature wheel-legs for locomotion. Yet, our control method is able to compensate for these limitations. We demonstrate fully autonomous robot mobility in a sewer pipe network, without any visual aid or power-hungry image processing. The control algorithm allows the robot to correctly recognise each local network configuration, and to make appropriate decisions accordingly. The control strategy was tested using the physical micro robot in a laboratory pipe network. In both simulation and experiment, the robot autonomously and exhaustively explored an unknown pipe network without missing any pipe section while avoiding obstacles. This is a significant advance towards fully autonomous inspection robot systems for sewer pipe networks.

Invasive meningococcal disease in Malaysia, Philippines, Thailand, and Vietnam: An Asia-Pacific expert group perspective on current epidemiology and vaccination policies.

Invasive meningococcal disease (IMD) imposes a significant burden on the global community due to its high case fatality rate (4-20%) and the risk of long-term sequelae for one in five survivors. An expert group meeting was held to discuss the epidemiology of IMD and immunization policies in Malaysia, Philippines, Thailand, and Vietnam. Most of these countries do not include meningococcal immunization in their routine vaccination programs, except for high-risk groups such as immunocompromised people and pilgrims. It is difficult to estimate the epidemiology of IMD in the highly diverse Asia-Pacific region, but available evidence indicate serogroup B is increasingly dominant. Disease surveillance systems differ by country. IMD is not a notifiable disease in some of them. Without an adequate surveillance system in the region, the risk and the burden of IMD might well be underestimated. With the availability of new combined meningococcal vaccines and the World Health Organization roadmap to defeat bacterial meningitis by 2030, a better understanding of the epidemiology of IMD in the Asia-Pacific region is needed.

Generation of a Maximally Entangled State Using Collective Optical Pumping.

We propose and implement a novel scheme for dissipatively pumping two qubits into a singlet Bell state. The method relies on a process of collective optical pumping to an excited level, to which all states apart from the singlet are coupled. We apply the method to deterministically entangle two trapped ^{40}Ca^{+} ions. Within 16 pumping cycles, an initially separable state is transformed into one with 83(1)% singlet fidelity, and states with initial fidelity of ⪆70% converge onto a fidelity of 93(1)%. We theoretically analyze the performance and error susceptibility of the scheme and find it to be insensitive to a large class of experimentally relevant noise sources.

Isomer-selected ion-molecule reactions of acetylene cations with propyne and allene.

One of the fundamental goals of chemistry is to determine how molecular structure influences interactions and leads to different reaction products. Studies of isomer-selected and resolved chemical reactions can shed light directly on how form leads to function. In the following, we present the results of gas-phase reactions between acetylene cations (C2D2+) with two different isomers of C3H4: propyne (DC3D3) and allene (H2C3H2). Our highly controlled, trapped-ion environment allows for precise determination of reaction products and kinetics. From these results, we can infer details of the underlying reaction dynamics of C2H2+ + C3H4. Through the synergy of experimental results and high-level quantum chemical potential energy surface calculations, we are able to identify distinct reaction mechanisms for the two isomers. We find long-range charge exchange with no complex formation is favored for allene, whereas charge exchange leads to an intermediate reaction complex for propyne and thus, different products. Therefore, this reaction displays a pronounced isomer-selective bi-molecular reactive process.

Smoke-free environment policy in Vietnam: what did people see and how did they react when they visited various public places?

INTRODUCTION: Since Vietnam has signed WHO framework on tobacco control (FCTC) in 2003 and has issued tobacco control law in 2013, there has been little research concerning about what impacts smoke-free regulations have had on public compliance. The objective of this study was to assess public exposure to secondhand smoke and reaction toward smoke-free policy regulations in Vietnam and the associated factor. METHODS: Using the design of GATS (Global Adult Tobacco Survey), a nationally representative sample of 8,996 adults were approached for data collection. Logistic regression was used to examine the associated factor. RESULTS: The study revealed that the prevalence of respondents exposed to secondhand smoke was much higher in bars/café/tea shops (90.07%) and restaurants (81.81%) than in any other public places, universities (36.70%), government buildings (31.12%), public transport (20.04%), healthcare facilities (17.85%) and schools (15.84%). 13.23% of respondents saw smokers violate smoke-free regulations. Among those who saw them violate smoke-free regulations, just one-third cautioned them to stop smoking. Strikingly, a higher rate of cautioning smokers to stop smoking was observed among the older, married, and better educated respondents. Respondents who were married, better educated and in lower economic status were more likely to remind smokers to stop smoking. CONCLUSIONS: The study has called for strengthening two of the six MPOWER (Monitor, Protect, Offer, Warn, Enforce and Raise) components of the tobacco free initiative introduced by WHO, Monitoring tobacco use and prevention policies and Protecting people from tobacco smoke.

Encoding a qubit in a trapped-ion mechanical oscillator.

The stable operation of quantum computers will rely on error correction, in which single quantum bits of information are stored redundantly in the Hilbert space of a larger system. Such encoded qubits are commonly based on arrays of many physical qubits, but can also be realized using a single higher-dimensional quantum system, such as a harmonic oscillator1-3. In such a system, a powerful encoding has been devised based on periodically spaced superpositions of position eigenstates4-6. Various proposals have been made for realizing approximations to such states, but these have thus far remained out of reach7-11. Here we demonstrate such an encoded qubit using a superposition of displaced squeezed states of the harmonic motion of a single trapped 40Ca+ ion, controlling and measuring the mechanical oscillator through coupling to an ancillary internal-state qubit12. We prepare and reconstruct logical states with an average squared fidelity of 87.3 ± 0.7 per cent. Also, we demonstrate a universal logical single-qubit gate set, which we analyse using process tomography. For Pauli gates we reach process fidelities of about 97 per cent, whereas for continuous rotations we use gate teleportation and achieve fidelities of approximately 89 per cent. This control method opens a route for exploring continuous variable error correction as well as hybrid quantum information schemes using both discrete and continuous variables13. The code states also have direct applications in quantum sensing, allowing simultaneous measurement of small displacements in both position and momentum14,15.

Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort Study of 10 964 Patients in Vietnam.

BACKGROUND: Tuberculosis is the leading infectious cause of death. Steep reductions in tuberculosis-related mortality are required to realize the World Health Organization's "End Tuberculosis Strategy." However, accurate mortality estimates are lacking in many countries, particularly following discharge from care. This study aimed to establish the mortality rate among patients with pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this population. METHODS: We conducted a prospective cohort study among adult patients treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam. People living in the same households were recruited as controls. Participants were re-interviewed and their survival was established at least 2 years after their treatment with an 8-month standardized regimen. The presence of relapse was established by linking identifying data on patients and controls to clinic registries. Verbal autopsies were performed. The cumulative mortality among patients was compared to that among a control population, adjusting for age and gender. RESULTS: We enrolled 10964 patients and 25707 household controls. Among enrolled tuberculosis patients, 9% of patients died within a median follow-up period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge. The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among patients with tuberculosis, compared to the control population. Tuberculosis was the likely cause of death for 44.7% of these deceased patients. CONCLUSIONS: Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.

DS1/OsEMF1 interacts with OsARF11 to control rice architecture by regulation of brassinosteroid signaling.

BACKGROUND: Plant height and leaf angle are important determinants of yield in rice (Oryza sativa L.). Genes involved in regulating plant height and leaf angle were identified in previous studies; however, there are many remaining unknown factors that affect rice architecture. RESULTS: In this study, we characterized a dwarf mutant named ds1 with small grain size and decreased leaf angle,selected from an irradiated population of ssp. japonica variety Nanjing35. The ds1 mutant also showed abnormal floral organs. ds1 plants were insensitive to BL treatment and expression of genes related to BR signaling was changed. An F2 population from a cross between ds1 and indica cultivar 93-11 was used to fine map DS1 and to map-based clone the DS1 allele, which encoded an EMF1-like protein that acted as a transcriptional regulator. DS1 was constitutively expressed in various tissues, and especially highly expressed in young leaves, panicles and seeds. We showed that the DS1 protein interacted with auxin response factor 11 (OsARF11), a major transcriptional regulator of plant height and leaf angle, to co-regulate D61/OsBRI1 expression. These findings provide novel insights into understanding the molecular mechanisms by which DS1 integrates auxin and brassinosteroid signaling in rice. CONCLUSION: The DS1 gene encoded an EMF1-like protein in rice. The ds1 mutation altered the expression of genes related to BR signaling, and ds1 was insensitive to BL treatment. DS1 interacts with OsARF11 to co-regulate OsBRI1 expression.

Assessing the costs of disposable and reusable supplies wasted during surgeries.

BACKGROUND: The management of disposable and reusable supplies might have an impact on the cost efficiency of the Operating Room (OR). This study aimed to evaluate the cost and reasons for wasted supplies in the OR during surgical procedures. METHODS: We conducted an observational and prospective study in a French university hospital. We assessed the cost of wasted supplies in the OR (defined by opened unused devices), the reasons for the wastage, and the circulator retrievals. At the end, we assessed the perception of surgeons and nurses relative to the supply wastage. RESULTS: Fifty routine procedures and five non-scheduled procedures were observed in digestive (n = 20), urologic (n = 20) and gynecologic surgery (n = 15). The median cost [IQR] of open unused devices was €4.1 [0.5; 10.5] per procedure. Wasted supplies represented up to 20.1% of the total cost allocated to surgical supplies. Considering the 8000 surgical procedures performed in these three surgery departments, the potential annual cost savings were 100 000€. The most common reason of wastage was an anticipation of the surgeon's needs. The circulating nurse spent up to 26.3% of operative time outside of the OR, mainly attending to an additional demand from the surgeon (30%). Most of the survey respondents (68%) agreed that knowing supply prices would change their behavior. CONCLUSIONS: This study showed the OR is a major source of wasted hospital expenditure and an area wherein an intervention would have a significant impact. Reducing wasted supplies could improve the cost efficiency of the OR and also decrease its ecological impact.

Development of real-time PCR for detection and quantitation of Streptococcus parauberis.

Streptococcus parauberis is an increasing threat to aquaculture of olive flounder, Paralichthys olivaceus Temminck & Schlegel, in South Korea. We developed a real-time polymerase chain reaction (PCR) method using the TaqMan probe assay to detect and quantify S. parauberis by targeting the gyrB gene sequences, which are effective for molecular analysis of the genus Streptococcus. Our real-time PCR assay is capable of detecting 10 fg of genomic DNA per reaction. The intra- and interassay coefficient of variation (CV) values ranged from 0.42-1.95%, demonstrating that the assay has good reproducibility. There was not any cross-reactivity to Streptococcus iniae or to other streptococcal/lactococcal fish pathogens, such as S. agalactiae and Lactococcus garvieae, indicating that the assay is highly specific to S. parauberis. The results of the real-time PCR assay corresponded well to those of conventional culture assays for S. parauberis from inoculated tissue homogenates (r = 0.957; P < 0.05). Hence, this sensitive and specific real-time PCR is a valuable tool for diagnostic quantitation of S. parauberis in clinical samples.

Microwaves Probe Dipole Blockade and van der Waals Forces in a Cold Rydberg Gas.

We show that microwave spectroscopy of a dense Rydberg gas trapped on a superconducting atom chip in the dipole blockade regime reveals directly the dipole-dipole many-body interaction energy spectrum. We use this method to investigate the expansion of the Rydberg cloud under the effect of repulsive van der Waals forces and the breakdown of the frozen gas approximation. This study opens a promising route for quantum simulation of many-body systems and quantum information transport in chains of strongly interacting Rydberg atoms.