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1.
Small Methods ; : e2400172, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38807542

ABSTRACT

Delicately manipulating nanomorphology is recognized as a vital and effective approach to enhancing the performance and stability of organic solar cells (OSCs). However, the complete removal of solvent additives with high boiling points is typically necessary to maintain the operational stability of the device. In this study, two commercially available organic intermediates, namely thieno[3,2-b]thiophene (TT) and 3,6-dibromothieno[3,2-b]thiophene (TTB) are introduced, as solid additives in OSCs. The theoretical simulations and experimental results indicate that TT and TTB may exhibit stronger intermolecular interactions with the acceptor Y6 and donor PM6, respectively. This suggests that the solid additives (SAs) can selectively intercalate between Y6 and PM6 molecules, thereby improving the packing order and crystallinity. As a result, the TT-treated PM6:Y6 system exhibits a favorable morphology, improved charge carrier mobility, and minimal charge recombination loss. These characteristics contribute to an impressive efficiency of 17.75%. Furthermore, the system demonstrates exceptional thermal stability (T80 > 2800 h at 65 °C) and outstanding photostability. The universal applicability of TT treatment is confirmed in OSCs employing D18:L8-BO, achieving a significantly higher PCE of 18.3%. These findings underscore the importance of using appropriate solid additives to optimize the blend morphology of OSCs, thereby improving photovoltaic performance and thermal stability.

2.
bioRxiv ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38712189

ABSTRACT

Keyboard typing with finger movements is a versatile digital interface for users with diverse skills, needs, and preferences. Currently, such an interface does not exist for people with paralysis. We developed an intracortical brain-computer interface (BCI) for typing with attempted flexion/extension movements of three finger groups on the right hand, or both hands, and demonstrated its flexibility in two dominant typing paradigms. The first paradigm is "point-and-click" typing, where a BCI user selects one key at a time using continuous real-time control, allowing selection of arbitrary sequences of symbols. During cued character selection with this paradigm, a human research participant with paralysis achieved 30-40 selections per minute with nearly 90% accuracy. The second paradigm is "keystroke" typing, where the BCI user selects each character by a discrete movement without real-time feedback, often giving a faster speed for natural language sentences. With 90 cued characters per minute, decoding attempted finger movements and correcting errors using a language model resulted in more than 90% accuracy. Notably, both paradigms matched the state-of-the-art for BCI performance and enabled further flexibility by the simultaneous selection of multiple characters as well as efficient decoder estimation across paradigms. Overall, the high-performance interface is a step towards the wider accessibility of BCI technology by addressing unmet user needs for flexibility.

3.
JAMA Netw Open ; 7(5): e2411140, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38758557

ABSTRACT

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.


Subject(s)
Infant, Extremely Premature , Umbilical Cord Clamping , Humans , Infant, Newborn , Female , Male , Umbilical Cord Clamping/methods , Canada , Respiration, Artificial/methods , Cerebral Intraventricular Hemorrhage/prevention & control , Umbilical Cord , Continuous Positive Airway Pressure/methods , Gestational Age , Time Factors , United States
4.
medRxiv ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38645254

ABSTRACT

Brain-computer interfaces can enable rapid, intuitive communication for people with paralysis by transforming the cortical activity associated with attempted speech into text on a computer screen. Despite recent advances, communication with brain-computer interfaces has been restricted by extensive training data requirements and inaccurate word output. A man in his 40's with ALS with tetraparesis and severe dysarthria (ALSFRS-R = 23) was enrolled into the BrainGate2 clinical trial. He underwent surgical implantation of four microelectrode arrays into his left precentral gyrus, which recorded neural activity from 256 intracortical electrodes. We report a speech neuroprosthesis that decoded his neural activity as he attempted to speak in both prompted and unstructured conversational settings. Decoded words were displayed on a screen, then vocalized using text-to-speech software designed to sound like his pre-ALS voice. On the first day of system use, following 30 minutes of attempted speech training data, the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. On the second day, the size of the possible output vocabulary increased to 125,000 words, and, after 1.4 additional hours of training data, the neuroprosthesis achieved 90.2% accuracy. With further training data, the neuroprosthesis sustained 97.5% accuracy beyond eight months after surgical implantation. The participant has used the neuroprosthesis to communicate in self-paced conversations for over 248 hours. In an individual with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore naturalistic communication after a brief training period.

5.
Adv Mater ; : e2313393, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573779

ABSTRACT

The meta-stable active layer morphology of organic solar cells (OSCs) is identified as the main cause of the rapid burn-in loss of power conversion efficiency (PCE) during long-term device operation. However, effective strategies to eliminate the associated loss mechanisms from the initial stage of device operation are still lacking, especially for high-efficiency material systems. Herein, the introduction of molecularly engineered dimer acceptors with adjustable thermal transition properties into the active layer of OSCs to serve as supramolecular stabilizers for regulating the thermal transitions and optimizing the crystallization of the absorber composites is reported. By establishing intimate π-π interactions with small-molecule acceptors, these stabilizers can effectively reduce the trap-state density (Nt) in the devices to achieve excellent PCEs over 19%. More importantly, the low Nt associated with an initially optimized morphology can be maintained under external stresses to significantly reduce the PCE burn-in loss in devices. This research reveals a judicious approach to improving OPV stability by establishing a comprehensive correlation between material properties, active-layer morphology, and device performance, for developing burn-in-free OSCs.

6.
Nucl Med Commun ; 45(6): 465-473, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38465420

ABSTRACT

Targeted alpha therapy (TAT) is a promising form of oncology treatment utilising alpha-emitting radionuclides that can specifically accumulate at disease sites. The high energy and high linear energy transfer associated with alpha emissions causes localised damage at target sites whilst minimising that to surrounding healthy tissue. The lack of appropriate radionuclides has inhibited research in TAT. The identification of appropriate radionuclides should be primarily a function of the radionuclide's nuclear decay properties, and not their biochemistry or economic factors since these last two factors can change; however, the nuclear decay properties are fixed to that nuclide. This study has defined and applied a criterion based on nuclear decay properties useful for TAT. This down-selection exercise concluded that the most appropriate radionuclides are: 149 Tb, 211 At/ 211 Po, 212 Pb/ 212 Bi/ 212 Po, 213 Bi/ 213 Po, 224 Ra, 225 Ra/ 225 Ac/ 221 Fr, 226 Ac/ 226 Th, 227 Th/ 223 Ra/ 219 Rn, 229 U, 230 U/ 226 Th, and 253 Fm, the majority of which have previously been considered for TAT. 229 U and 253 Fm have been newly identified and could become new radionuclides of interest for TAT, depending on their decay chain progeny.


Subject(s)
Alpha Particles , Radioisotopes , Alpha Particles/therapeutic use , Radioisotopes/therapeutic use , Humans , Radiochemistry
7.
Langmuir ; 40(9): 4772-4778, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38381871

ABSTRACT

Self-assembled monolayers (SAMs) emerging as promising hole-selective layers (HSLs) are advantageous for facile processability, low cost, and minimal material consumption in the fabrication of both perovskite solar cells (PSCs) and organic solar cells (OSCs). However, owing to the different nature between perovskites and organic semiconductors, few SAMs were reported to effectively accommodate both PSCs and OSCs at the same time. In this regard, a universally applicable SAM that can accommodate both perovskites and organic semiconductors could be desirable for simplifying cell manufacturing, especially from an industrial perspective. In this work, we designed a SAM, TDPA-Cl by introducing chlorinated phenothiazine as the headgroup and linking with anchor phosphonic acid through a butyl chain. The resulting dense SAM was carefully characterized in terms of molecular bonding, surface morphology, and packing density, and its functions in OSCs and PSCs were discussed from the aspects of interactions with the absorber layer, energy level alignment, and charge-selective dipoles. The PM6:Y6-based OSCs with TDPA-Cl SAM as the HSL showed a superior performance to those with PEDOT:PSS. Furthermore, the universality was proved with an efficiency of 17.4% in the D18:Y6 system. In PSCs, the TDPA-Cl-based devices delivered a better performance of 22.4% than the PTAA-based devices (20.8%) with improved processability and reproducibility. This work represents a SAM with reasonably good compromise between the differing requirements of OSCs and PSCs.

8.
bioRxiv ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38370697

ABSTRACT

People with paralysis express unmet needs for peer support, leisure activities, and sporting activities. Many within the general population rely on social media and massively multiplayer video games to address these needs. We developed a high-performance finger brain-computer-interface system allowing continuous control of 3 independent finger groups with 2D thumb movements. The system was tested in a human research participant over sequential trials requiring fingers to reach and hold on targets, with an average acquisition rate of 76 targets/minute and completion time of 1.58 ± 0.06 seconds. Performance compared favorably to previous animal studies, despite a 2-fold increase in the decoded degrees-of-freedom (DOF). Finger positions were then used for 4-DOF velocity control of a virtual quadcopter, demonstrating functionality over both fixed and random obstacle courses. This approach shows promise for controlling multiple-DOF end-effectors, such as robotic fingers or digital interfaces for work, entertainment, and socialization.

9.
ChemSusChem ; : e202301559, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38372481

ABSTRACT

Organic solar cells (OSCs) have achieved remarkable power conversion efficiencies (PCEs) of over 19 % in the past few years due to the rapid development of non-fullerene acceptors (NFAs). However, the operational stability remains a great challenge that inhibits their commercialization. Recently, oligomeric NFAs (ONFAs) have attracted great attention, which not only can deliver excellent device performance, but also improve the thermal-/photo- stability of OSCs. This is attributed to the suppressed molecular diffusion of ONFAs associated with their high glass-transition temperature (Tg ) and improved thermodynamic properties of ONFAs. Herein, we focus on investigating the correction between the ONFA chemical structure, material properties, device performance, and stability. In addition, we also try to point out the challenges in synthesizing ONFAs and provide potential directions for future ONFA designs.

10.
Eur J Neurosci ; 59(9): 2403-2415, 2024 May.
Article in English | MEDLINE | ID: mdl-38385841

ABSTRACT

Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms. We investigated the role of prefrontocortical (PFC) N-methyl-D-aspartate receptors (NMDARs) in the pathophysiology and development of schizophrenia. We explored the potential therapeutic effects of cannabidiolic acid (CBDA) methyl ester (HU-580), an analogue of CBDA known to act as an agonist of the serotonin-1A receptor (5-HT1AR) and an antagonist of cannabinoid type 1 receptor (CB1R). C57BL/6 mice were intraperitoneally administered the NMDAR antagonist, dizocilpine (MK-801, .3 mg/kg) once daily for 17 days. After 7 days, they were concurrently given HU-580 (.01 or .05 µg/kg) for 10 days. Behavioural deficits were assessed at two time points. We conducted enzyme-linked immunosorbent assays to measure the concentration of PFC 5-HT1AR and CB1R. We found that MK-801 effectively induced schizophrenia-related behaviours including hyperactivity, social withdrawal, increased forced swim immobility, and cognitive deficits. We discovered that low-dose HU-580 (.01 µg/kg), but not the high dose (.05 µg/kg), attenuated hyperactivity, forced swim immobility and cognitive deficits, particularly in female mice. Our results revealed that MK-801 downregulated both CB1R and 5-HT1AR, an effect that was blocked by both low- and high-dose HU-580. This study sheds light on the potential antipsychotic properties of HU-580, particularly in the context of NMDAR-induced dysfunction. Our findings could contribute significantly to our understanding of schizophrenia pathophysiology and offer a promising avenue for exploring the therapeutic potential of HU-580 and related compounds in alleviating symptoms.


Subject(s)
Disease Models, Animal , Dizocilpine Maleate , Mice, Inbred C57BL , Receptor, Cannabinoid, CB1 , Receptor, Serotonin, 5-HT1A , Schizophrenia , Animals , Schizophrenia/drug therapy , Schizophrenia/chemically induced , Schizophrenia/metabolism , Dizocilpine Maleate/pharmacology , Receptor, Serotonin, 5-HT1A/metabolism , Receptor, Serotonin, 5-HT1A/drug effects , Male , Mice , Female , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB1/agonists , Cannabinoids/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Antipsychotic Agents/pharmacology
11.
Chem Rev ; 124(5): 2138-2204, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38421811

ABSTRACT

Interfacial engineering has long been a vital means of improving thin-film device performance, especially for organic electronics, perovskites, and hybrid devices. It greatly facilitates the fabrication and performance of solution-processed thin-film devices, including organic field effect transistors (OFETs), organic solar cells (OSCs), perovskite solar cells (PVSCs), and organic light-emitting diodes (OLEDs). However, due to the limitation of traditional interfacial materials, further progress of these thin-film devices is hampered particularly in terms of stability, flexibility, and sensitivity. The deadlock has gradually been broken through the development of self-assembled monolayers (SAMs), which possess distinct benefits in transparency, diversity, stability, sensitivity, selectivity, and surface passivation ability. In this review, we first showed the evolution of SAMs, elucidating their working mechanisms and structure-property relationships by assessing a wide range of SAM materials reported to date. A comprehensive comparison of various SAM growth, fabrication, and characterization methods was presented to help readers interested in applying SAM to their works. Moreover, the recent progress of the SAM design and applications in mainstream thin-film electronic devices, including OFETs, OSCs, PVSCs and OLEDs, was summarized. Finally, an outlook and prospects section summarizes the major challenges for the further development of SAMs used in thin-film devices.

12.
Chem Sci ; 15(8): 2778-2785, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38404377

ABSTRACT

Self-assembled monolayers (SAMs) have been widely employed as the bottom-contact hole-selective layer (HSL) in inverted perovskite solar cells (PSCs). Besides manipulating the electrical properties, molecularly engineering the SAM provides an opportunity to modulate the perovskite buried interface. Here, we successfully introduced Lewis-basic oxygen and sulfur heteroatoms through rational molecular design of asymmetric SAMs to obtain two novel multifunctional SAMs, CbzBF and CbzBT. Detailed characterization of single-crystal structures and device interfaces shows that enhanced packing, more effective ITO work function adjustment, and buried interface passivation were successfully achieved. Consequently, the champion PSC employing CbzBT showed an excellent power conversion efficiency (PCE) of 24.0% with a high fill factor of 84.41% and improved stability. This work demonstrates the feasibility of introducing defect-passivating heterocyclic groups into SAM molecules to help passivate the interfacial defects in PSCs. The insights gained from this molecular design strategy will accelerate the development of new multifunctional SAM HSLs for efficient PSCs.

13.
J Surg Oncol ; 129(5): 995-999, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38221660

ABSTRACT

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.


Subject(s)
Femur , Prosthesis Failure , Humans , Middle Aged , Prosthesis Design , Retrospective Studies , Femur/diagnostic imaging , Femur/surgery , Tibia/diagnostic imaging , Tibia/surgery , Reoperation , Treatment Outcome
14.
Sci Rep ; 14(1): 1598, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238386

ABSTRACT

Brain-computer interfaces have so far focused largely on enabling the control of a single effector, for example a single computer cursor or robotic arm. Restoring multi-effector motion could unlock greater functionality for people with paralysis (e.g., bimanual movement). However, it may prove challenging to decode the simultaneous motion of multiple effectors, as we recently found that a compositional neural code links movements across all limbs and that neural tuning changes nonlinearly during dual-effector motion. Here, we demonstrate the feasibility of high-quality bimanual control of two cursors via neural network (NN) decoders. Through simulations, we show that NNs leverage a neural 'laterality' dimension to distinguish between left and right-hand movements as neural tuning to both hands become increasingly correlated. In training recurrent neural networks (RNNs) for two-cursor control, we developed a method that alters the temporal structure of the training data by dilating/compressing it in time and re-ordering it, which we show helps RNNs successfully generalize to the online setting. With this method, we demonstrate that a person with paralysis can control two computer cursors simultaneously. Our results suggest that neural network decoders may be advantageous for multi-effector decoding, provided they are designed to transfer to the online setting.


Subject(s)
Brain-Computer Interfaces , Neural Networks, Computer , Humans , Movement , Functional Laterality , Hand , Paralysis , Brain
15.
Cardiology ; 149(1): 1-13, 2024.
Article in English | MEDLINE | ID: mdl-37952523

ABSTRACT

INTRODUCTION: Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients' biological age, and may exceed conventional risk scores in predicting the prognosis. Therefore, we wanted to investigate the prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). METHODS: Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: robust (1-3), vulnerable (4), and frail (5-9) and followed for 12 months. RESULTS: Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable, and 307 (68%) were robust. Frail patients were older (frail: 80.9 ± 5.7 years, vulnerable: 78.5 ± 5.5 years, and robust: 76.6 ± 4.9 years, p < 0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2%, and robust: 68.6%, p = 0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8%, and robust: 6.2%, p < 0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, the Global Registry of Acute Coronary Events (GRACE) score, and revascularisation (HR 2.67, 95% CI 1.30-5.50, p = 0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p = 0.893). CONCLUSIONS: Fifteen percent of patients ≥70 years old with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.


Subject(s)
Acute Coronary Syndrome , Frailty , Humans , Aged , Frailty/epidemiology , Frailty/complications , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/complications , Frail Elderly , Coronary Angiography , Prevalence
16.
Acta Medica Philippina ; : 1-23, 2024.
Article in English | WPRIM (Western Pacific) | ID: wpr-1011314

ABSTRACT

Background and Objective@#Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies.@*Methods@#We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty.@*Results@#Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve.@*Conclusion@#Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.


Subject(s)
Scabies , Ivermectin , Permethrin , Cost-Benefit Analysis
17.
Science ; 382(6674): 1073-1079, 2023 12.
Article in English | MEDLINE | ID: mdl-38033053

ABSTRACT

Skin-resident CD8+ T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (TRM1)] and interleukin-17 (IL-17)-producing (TRM17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that TRM1 and TRM17 cells navigate divergent trajectories to acquire tissue residency in the skin. TRM1 cells depend on a T-bet-Hobit-IL-15 axis, whereas TRM17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in TRM17 cells parallel to that induced by Hobit in TRM1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to TRM17 cell commitment. Accordingly, by targeting this pathway, skin TRM17 cells can be ablated without compromising their TRM1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity.


Subject(s)
CD8-Positive T-Lymphocytes , Immunologic Memory , Memory T Cells , Skin , CD8-Positive T-Lymphocytes/immunology , Memory T Cells/immunology , Skin/immunology , Humans , Th17 Cells/immunology , Inducible T-Cell Co-Stimulator Ligand/metabolism , Proto-Oncogene Proteins c-maf/metabolism , Interleukin-7/metabolism
18.
ArXiv ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37986728

ABSTRACT

Intracortical brain-computer interfaces (iBCIs) have shown promise for restoring rapid communication to people with neurological disorders such as amyotrophic lateral sclerosis (ALS). However, to maintain high performance over time, iBCIs typically need frequent recalibration to combat changes in the neural recordings that accrue over days. This requires iBCI users to stop using the iBCI and engage in supervised data collection, making the iBCI system hard to use. In this paper, we propose a method that enables self-recalibration of communication iBCIs without interrupting the user. Our method leverages large language models (LMs) to automatically correct errors in iBCI outputs. The self-recalibration process uses these corrected outputs ("pseudo-labels") to continually update the iBCI decoder online. Over a period of more than one year (403 days), we evaluated our Continual Online Recalibration with Pseudo-labels (CORP) framework with one clinical trial participant. CORP achieved a stable decoding accuracy of 93.84% in an online handwriting iBCI task, significantly outperforming other baseline methods. Notably, this is the longest-running iBCI stability demonstration involving a human participant. Our results provide the first evidence for long-term stabilization of a plug-and-play, high-performance communication iBCI, addressing a major barrier for the clinical translation of iBCIs.

19.
AJPM Focus ; 2(2): 100067, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37790637

ABSTRACT

Introduction: This mixed-methods study analyzed English-language U.S.-based Twitter posts related to E-cigarette use from February 2021. Methods: Posts were manually identified as health-related or not and, if health-related, whether they were posted by an E-cigarette user. A random selection of 1,000 health-related tweets from 986 unique E-cigarette users were qualitatively content analyzed for theory of planned behavior constructs as well as nature and tone of each tweet message. Using quantitative semantic network analysis, relationships among the identified topics and sentiment-specific conversation patterns were explored. Results: The most salient health-related conversation topics of E-cigarette users, health beliefs corresponding to each theory of planned behavior construct, and major motivational contexts of E-cigarette use were identified. Seven topics emerged in positive tweets: smoking cessation, social impact generation, controls over addiction, therapeutic effects on physical and mental health, social support, device attachment, and peer influence. Nine topics emerged in negative tweets: side effects on physical health, vaping addiction, lack of E-cigarette regulations, peer pressure, increased risk of COVID-19, side effects on mental health, no help in smoking cessation, social conflict, and polysubstance use. Most assertions for E-cigarette benefits were not substantiated. Jokes in tweets appeared to contribute to the view of vaping as an attractive, enjoyable, safe, and fun activity. Discussions about positive aspects of E-cigarette use were concentrated on a few related topics, whereas tweets discouraging E-cigarette use presented a diverse, less related set of topics. Conclusions: The results provide insights into the drivers of E-cigarette use behaviors. E-cigarette user perspectives gathered from social media may inform research to guide future prevention and cessation interventions.

20.
Int Marit Health ; 74(3): 161-170, 2023.
Article in English | MEDLINE | ID: mdl-37781941

ABSTRACT

BACKGROUND: There is a limited number of studies on the medical repatriation of seafarers. The aim of the study was to follow up on the previous 2010-2014 study using data from 2015-2019 to evaluate the epidemiology of medical repatriation among Filipino seafarers. MATERIALS AND METHODS: Data from medical repatriation records of Filipino seafarers from January 2015 to December 2019 were collected from various claims departments of different manning agencies in Manila, Philippines. RESULTS: Data from a total of 6,526 medical repatriation cases and 464,418 deployments in a 5-year period resulted in a medical repatriation rate calculated at 1.4%. We used the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) to determine the most common causes of repatriation. We found that these were musculoskeletal disorders, gastrointestinal problems, and traumatic injuries. The distribution of the specific illnesses per organ system is presented. CONCLUSIONS: Filipinos continue to represent the most numerous group of seafarers in the world. The continued profiling of health issues should lead to better health protocols and controlling medical costs. It should also lead to better prioritisation of health protection and care on board ships. Within the present 10-year database of medical repatriations coinciding with the implementation of Maritime Convention Labour Convention 2006, there is a compelling need to compare the two data sets to have an objective evaluation of the convention's projected goals.


Subject(s)
Naval Medicine , Ships , Humans , Follow-Up Studies , Philippines , Asian People
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