Tobacco use, trauma exposure and PTSD: a systematic review.

Tobacco use remains one of the most significant preventable public health problems globally and is increasingly concentrated among vulnerable groups, including those with trauma exposure or diagnosed with PTSD. The goal of this systematic review was to update and extend previous reviews. Of the 7224 publications that met the initial criteria, 267 were included in the review. Summary topic areas include conceptual frameworks for the relation between trauma or PTSD and tobacco use; associations between trauma exposure or PTSD and tobacco use; number and type of trauma exposures and tobacco use; PTSD symptoms and tobacco use; Treatment-related studies; and the examination of causal relations. Evidence continues to indicate that individuals exposed to trauma or diagnosed with PTSD are more likely to use tobacco products, more nicotine dependent and less likely to abstain from tobacco even when provided evidence-based treatments than individuals without trauma. The most commonly cited causal association proposed was use of tobacco for self-regulation of negative affect associated with trauma. A small proportion of the studies addressed causality and mechanisms of action. Future work should incorporate methodological approaches and measures from which we can draw causal conclusions and mechanisms to support the development of viable therapeutic targets.

The moving wave: Applications of the mobile EEG approach to study human attention.

Although historically confined to traditional research laboratories, electroencephalography (EEG) paradigms are now being applied to study a wide array of behaviors, from daily activities to specialized tasks in diverse fields such as sports science, neurorehabilitation, and education. This transition from traditional to real-world mobile research can provide new tools for understanding attentional processes as they occur naturally. Early mobile EEG research has made progress, despite the large size and wired connections. Recent developments in hardware and software have expanded the possibilities of mobile EEG, enabling a broader range of applications. Despite these advancements, limitations influencing mobile EEG remain that must be overcome to achieve adequate reliability and validity. In this review, we first assess the feasibility of mobile paradigms, including electrode selection, artifact correction techniques, and methodological considerations. This review underscores the importance of ecological, construct, and predictive validity in ensuring the trustworthiness and applicability of mobile EEG findings. Second, we explore studies on attention in naturalistic settings, focusing on replicating classic P3 component studies in mobile paradigms like stationary biking in our lab, and activities such as walking, cycling, and dual-tasking outside of the lab. We emphasize how the mobile approach complements traditional laboratory paradigms and the types of insights gained in naturalistic research settings. Third, we discuss promising applications of portable EEG in workplace safety and other areas including road safety, rehabilitation medicine, and brain-computer interfaces. In summary, this review explores the expanding possibilities of mobile EEG while recognizing the existing challenges in fully realizing its potential.

Hybrid surface implants: Influence of residual stress on mechanical behavior, evaluated by finite element analysis and validation by fatigue tests.

OBJECTIVES: To determine the influence of different surface roughness and residual stress of hybrid surface implants on their behavior and mechanical failure. METHODS: Three types of implants with different surface roughness were used as specimens: smooth, rough, and hybrid. A diffractometer was used to determine the residual stress of the implants according to their different surface treatment. These results were used as an independent variable in a finite element analysis that compared the three specimens to determine the von Mises stress transferred to the implants and supporting bone and the resulting microdeformations. Flexural strength and fatigue behavior tests were performed to compare the results of the three types of implants. RESULTS: Higher residual stress values were found for rough surfaces (p < 0.05, Student's t-test) compared to smooth surfaces, and both types of stress were different for the two types of hybrid implant surfaces. Finite element analysis found different von Mises stress and microdeformation results, both at the level of the implant and the bone, for the three types of implants under study. These results were correlated with the different flexural strength behaviors (lower resistance for hybrids and higher for rough surfaces, p < 0.05) and fatigue behavior (the rough implant had the longest fatigue life, while the hybrid implant exhibited the worst fatigue behavior). SIGNIFICANCE: The results show a trend toward a less favorable mechanical behavior of the hybrid implants related to the retention of different residual stresses caused by the surface treatment.

Osteoblastic and Bacterial Response of Hybrid Dental Implants.

Bacterial infections in dental implants generate peri-implantitis disease that causes bone loss and the mobility of the dental implant. It is well known that specific ranges of roughness favor the proliferation of bacteria, and it is for this reason that new dental implants called hybrids have appeared. These implants have a smooth area in the coronal part and a rough surface in the apical part. The objective of this research is the physico-chemical characterization of the surface and the osteoblastic and microbiological behavior. One-hundred and eighty discs of titanium grade 3 with three different surfaces (smooth, smooth-rough, and completely rough) were studied. The roughness was determined by white light interferometry, and the wettability and surface energy by the sessile drop technique and the application of Owens and Wendt equations. Human osteoblast SaOS-2 was cultured to determine cell adhesion, proliferation, and differentiation. Microbiological studies were performed with two common bacterial strains in oral infection, E. faecalis and S. gordonii, at different times of culture. The roughness obtained for the smooth surface was Sa = 0.23 and for the rough surface it was 1.98 µm. The contact angles were more hydrophilic for the smooth surface (61.2°) than for the rough surface (76.1°). However, the surface energy was lower for the rough surface (22.70 mJ/m2) in both its dispersive and polar components than the smooth surface (41.77 mJ/m2). Cellular activity in adhesion, proliferation, and differentiation was much higher on rough surfaces than on smooth surfaces. After 6 h of incubation, the osteoblast number in rough surfaces was more than 32% higher in relation to the smooth surface. The cell area in smooth surfaces was higher than rough surfaces. The proliferation increased and the alkaline phosphatase presented a maximum after 14 days, with the mineral content of the cells being higher in rough surfaces. In addition, the rough surfaces showed greater bacterial proliferation at the times studied and in the two strains used. Hybrid implants sacrifice the good osteoblast behavior of the coronal part of the implant in order to obstruct bacterial adhesion. The following fact should be considered by clinicians: there is a possible loss of bone fixation when preventing peri-implantitis.

Safety and Quality Issues of Counterfeit Lithium-Ion Cells.

Lithium-ion batteries continue to transform consumer electronics, mobility, and energy storage sectors, and the applications and demands for batteries keep growing. Supply limitations and costs may lead to counterfeit cells in the supply chain that could affect quality, safety, and reliability of batteries. Our research included studies of counterfeit and low-quality lithium-ion cells, and our observations on the differences between these and original ones, as well as the significant safety implications, are discussed. The counterfeit cells did not include internal protective devices such as the positive temperature coefficient or current interrupt devices that typically offer protection against external short circuits and overcharge conditions, respectively, in cells from original manufacturers. Poor-quality materials and lack of engineering knowledge were also evident on analyses of the electrodes and separators from low-quality manufacturers. When the low-quality cells were subjected to off-nominal conditions, they experienced high temperature, electrolyte leakage, thermal runaway, and fire. In contrast, the authentic lithium-ion cells performed as expected. Recommendations are provided to identify and avoid counterfeit and low-quality lithium-ion cells and batteries.

Corrosion Resistance and Titanium Ion Release of Hybrid Dental Implants.

One of the strategies for the fight against peri-implantitis is the fabrication of titanium dental implants with the part close to the neck without roughness. It is well known that roughness favors osseointegration but hinders the formation of biofilm. Implants with this type of structure are called hybrid dental implants, which sacrifice better coronal osseointegration for a smooth surface that hinders bacterial colonization. In this contribution, we have studied the corrosion resistance and the release of titanium ions to the medium of smooth (L), hybrid (H), and rough (R) dental implants. All implants were identical in design. Roughness was determined with an optical interferometer and residual stresses were determined for each surface by X-ray diffraction using the Bragg-Bentano technique. Corrosion studies were carried out with a Voltalab PGZ301 potentiostat, using Hank's solution as an electrolyte at a temperature of 37 °C. Open-circuit potentials (Eocp), corrosion potential (Ecorr), and current density (icorr) were determined. Implant surfaces were observed by JEOL 5410 scanning electron microscopy. Finally, for each of the different dental implants, the release of ions into Hank's solution at 37 °C at 1, 7, 14, and 30 days of immersion was determined by ICP-MS. The results, as expected, show a higher roughness of R with respect to L and compressive residual stresses of -201.2 MPa and -20.2 MPa, respectively. These differences in residual stresses create a potential difference in the H implant corresponding to Eocp of -186.4 mV higher than for the L and R of -200.9 and -192.2 mV, respectively. The corrosion potentials and current intensity are also higher for the H implants (-223 mV and 0.069 µA/mm2) with respect to the L (-280 mV and 0.014 µA/mm2 and R (-273 mV and 0.019 µA/mm2). Scanning electron microscopy revealed pitting in the interface zone of the H implants and no pitting in the L and R dental implants. The titanium ion release values to the medium are higher in the R implants due to their higher specific surface area compared to the H and L implants. The maximum values obtained are low, not exceeding 6 ppb in 30 days.

In Situ Gas Analysis and Fire Characterization of Lithium-Ion Cells During Thermal Runaway Using an Environmental Chamber.

An experimental apparatus and a standard operating procedure (SOP) are developed to collect time-resolved data on the gas compositions and fire characteristics during and post-thermal runaway of lithium-ion battery (LIB) cells. A 18650 cylindrical cell is conditioned to a desired state-of-charge (SOC; 30%, 50%, 75%, and 100%) before each experiment. The conditioned cell is forced into a thermal runaway by an electrical heating tape at a constant heating rate (10 °C/min) in an environmental chamber (volume: ~600 L). The chamber is connected to a Fourier transform infrared (FTIR) gas analyzer for real-time concentration measurements. Two camcorders are used to record major events, such as cell venting, thermal runaway, and the subsequent burning process. The conditions of the cell, such as surface temperature, mass loss, and voltage, are also recorded. With the data obtained, cell pseudo-properties, venting gas compositions, and venting mass rate can be deduced as functions of cell temperature and cell SOC. While the test procedure is developed for a single cylindrical cell, it can be readily extended to test different cell formats and study fire propagation between multiple cells. The collected experimental data can also be used for the development of numerical models for LIB fires.

Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

Efficacy and Safety of the Adjuvant Use of Probiotic Bacillus clausii Strains in Pediatric Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVES: Current irritable bowel syndrome (IBS) treatments have limited efficacy and probiotics like Bacillus clausii (B. clausii) were found to be effective in the management of several gastrointestinal disorders. This phase III trial assessed the efficacy and safety of adding B. clausii (four strains: O/C, N/R, SIN, T), versus placebo, to conventional treatment of pediatric IBS in Mexico. METHODS: Patients aged 6-17 years 11 months with IBS (Rome IV) for at least 2 months were randomized to receive either B. clausii (oral suspension, total dose 4 billion spores/day) or placebo once daily for 8 weeks. All patients also received conventional treatment. The primary endpoint was the difference in the proportion of patients with clinical improvements at Week 8 (Global Assessment Questions [GAQ]). Secondary endpoints included responders by Subject's Global Assessment of Relief for Children with IBS (SGARC); number/consistency of stools; abdominal distention/bloating; abdominal pain/intensity; and IBS behavior. RESULTS: 73.6% (95% confidence interval [CI] 67.3-80.0; B. clausii n = 129) and 78.5% (95% CI 72.5-84.4; placebo n = 130) of patients had symptom improvement (p = 0.8182). For Week 8 SGARC, 19.2% (B. clausii) and 20.9% (placebo) reported complete symptom relief. Stool evaluations, bloating, abdominal pain/intensity, and IBS behavior were similar between groups. Both treatments were well tolerated. CONCLUSION: No significant differences in efficacy between B. clausii and placebo were demonstrated in addition to conventional treatment. The sample size calculation was based on an expected placebo/conventional treatment response of 30-40%. However, the actual treatment response observed was 80% and, thus, a study with larger population would be warranted. In addition, this study was conducted during the COVID-19 pandemic, when such controlled social conditions may have resulted in better diet, greater family stability, less psychological stress, and lower risk of infections exacerbating IBS, thereby improving symptoms in both groups. EUDRACT NUMBER: 2018-004519-31.

Formación de grado en cuidados paliativos en las universidades de la Comunidad Autónoma de Madrid. Estudio descriptivo / Palliative care degree training at universities in the Autonomous Community of Madrid. A descriptive study

Introducción: En vista del desarrollo que se está produciendo en cuidados paliativos y las recomendaciones formativas llevadas a cabo por distintos planes estratégicos internacionales, nacionales y autonómicos, la Asociación Madrileña de Cuidados Paliativos (AMCP) realizó este estudio con el objetivo de definir la situación actual de la formación en cuidados paliativos en la Comunidad de Madrid en los grados de medicina, enfermería, psicología y trabajo social. Material y métodos: Para ello, se elaboró un cuestionario con los datos considerados relevantes según la evidencia, que fue enviado a las diferentes universidades para su cumplimentación durante el año 2021. En el caso de no obtener respuesta, la información se completó por parte del equipo investigador revisando las guías docentes oficiales.Resultados: A partir de los datos obtenidos provenientes de 46 grados universitarios analizados, encontramos que la formación específica en cuidados paliativos se encuentra en el 71,7 % de las universidades. En el 69,7 % de estas, esta formación no se imparte en una asignatura independiente; la media de ECTS (European Credit Transfer and Accumulation System) atribuidos a esta formación es de 3. En más de la mitad de estudios no hay prácticas obligatorias y los talleres o seminarios solo se encuentran en el 39,5 % de los planes formativos. El seminario más frecuente es el de “Malas noticias” en todos los estudios. Los temas más tratados son el “Abordaje emocional de paciente y familia”, seguido por el “Manejo de síntomas” y los “Aspectos éticos”. Conclusión: La formación en cuidados paliativos se hace presente cada vez más frecuentemente en las universidades madrileñas, habitualmente como parte de otras asignaturas. Los talleres, seminarios y las prácticas obligatorias son escasos. Los profesores son sobre todo titulares y sin formación específica. Hay que seguir trabajando para alcanzar los estándares marcados por las sociedades científicas respecto a formación. (AU)

Introduction: In view of the development that is taking place in the field of palliative care and the training recommendations given by different international, national and regional strategic plans, the Madrilenian Association of Palliative Care (AMCP) carried out this study with the aim of defining the current situation of training in palliative care within the medicine, nursing, psychology and social work degrees taught at universities in the Community of Madrid. Material and methods: To this end, a questionnaire was drawn up with the data considered relevant according to the evidence, which was sent to the different universities to be completed during the year 2021. If no response was received, the information was completed by the research team by reviewing the relevant official teaching guides. Results: From the data obtained from all 46 university degrees analysed, we found that specific training in palliative care is found in 71.7 % of universities. In 69.7 % of these, palliative care is not taught as an independent subject matter; the average number of ECTS (European Credit Transfer and Accumulation System) attributed to this training is 3. In more than 50 % of cases there are no compulsory internships, and workshops or seminars are only found in 39.5 % of the curricula. The most frequently taught seminar is “Breaking bad news”. The most frequently covered topics are “Emotional support of patients and their families”, followed by “Symptom management” and “Ethical aspects”. Conclusion: Training in palliative care is increasingly present in Madrid universities, usually as part of other subjects. Workshops, seminars, and compulsory internships are scarce. Teachers are mostly tenured, without specific training. We must continue working to achieve the standards set by scientific societies regarding training. (AU)

Frequency and polarization emission properties of a photon-pair source based on a photonic crystal fiber.

In this work, we experimentally demonstrate a photon-pair source with correlations in the frequency and polarization degrees of freedom. We base our source on the spontaneous four-wave mixing (SFWM) process in a photonic crystal fiber. We show theoretically that the two-photon state is the coherent superposition of up to six distinct SFWM processes, each corresponding to a distinct combination of polarizations for the four waves involved and giving rise to an energy-conserving pair of peaks. Our experimental measurements, both in terms of single and coincidence counts, confirm the presence of these pairs of peaks, while we also present related numerical simulations with excellent experiment-theory agreement. We explicitly show how the pump frequency and polarization may be used to effectively control the signal-idler photon-pair properties, defining which of the six processes can participate in the overall two-photon state and at which optical frequencies. We analyze the signal-idler correlations in frequency and polarization, and in terms of fiber characterization, we input the SFWM-peak experimental data into a genetic algorithm which successfully predicts the values of the parameters that characterize the fiber cross section, as well as predict the particular SFWM process associated with a given pair of peaks. We believe our work will help advance the exploitation of photon-pair correlations in the frequency and polarization degrees of freedom.

Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer.

Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone. The approved niclosamide formulation has poor oral bioavailability. The primary objective of this phase Ib trial was to identify a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of a novel reformulated orally-bioavailable niclosamide/PDMX1001 in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC). Eligible patients had progressing CRPC, adequate end-organ function, and no prior treatment with abiraterone or ketoconazole. Patients were treated with escalating doses of niclosamide/PDMX1001 and standard doses of abiraterone and prednisone. Peak and trough niclosamide plasma levels were measured. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and Prostate Cancer Working Group 2 criteria were used to evaluate toxicities and responses. Nine patients with metastatic CRPC were accrued, with no dose-limiting toxicities observed at all dose levels. The recommended Phase II dose of niclosamide/PDMX1001 was 1200 mg orally (PO) three times daily plus abiraterone 1000 mg PO once daily and prednisone 5 mg PO twice daily. Trough and peak niclosamide concentrations exceeded the therapeutic threshold of > 0.2 µM. The combination was well tolerated with most frequent adverse effects of diarrhea. Five out of eight evaluable patients achieved a PSA response; two achieved undetectable PSA and radiographic response. A novel niclosamide/PDMX1001 reformulation achieved targeted plasma levels when combined with abiraterone and prednisone, and was well tolerated. Further study of niclosamide/PDMX1001 with this combination is warranted.

EEG in motion: Using an oddball task to explore motor interference in active skateboarding.

Recent advancements in portable computer devices have opened new avenues in the study of human cognition outside research laboratories. This flexibility in methodology has led to the publication of several electroencephalography studies recording brain responses in real-world scenarios such as cycling and walking outside. In the present study, we tested the classic auditory oddball task while participants moved around an indoor running track using an electric skateboard. This novel approach allows for the study of attention in motion while virtually removing body movement. Using the skateboard auditory oddball paradigm, we found reliable and expected standard-target differences in the P3 and MMN/N2b event-related potentials. We also recorded baseline electroencephalography activity and found that, compared to this baseline, alpha power is attenuated in frontal and parietal regions during skateboarding. In order to explore the influence of motor interference in cognitive resources during skateboarding, we compared participants' preferred riding stance (baseline level of riding difficulty) versus their non-preferred stance (increased level of riding difficulty). We found that an increase in riding difficulty did not modulate the P3 and tonic alpha amplitude during skateboard motion. These results suggest that increases in motor demands might not lead to reductions in cognitive resources as shown in previous literature.

Combining Wearable Devices and Mobile Surveys to Study Child and Youth Development in Malawi: Implementation Study of a Multimodal Approach.

BACKGROUND: Multimodal approaches have been shown to be a promising way to collect data on child development at high frequency, combining different data inputs (from phone surveys to signals from noninvasive biomarkers) to understand children's health and development outcomes more integrally from multiple perspectives. OBJECTIVE: The aim of this work was to describe an implementation study using a multimodal approach combining noninvasive biomarkers, social contact patterns, mobile surveying, and face-to-face interviews in order to validate technologies that help us better understand child development in poor countries at a high frequency. METHODS: We carried out a mixed study based on a transversal descriptive analysis and a longitudinal prospective analysis in Malawi. In each village, children were sampled to participate in weekly sessions in which data signals were collected through wearable devices (electrocardiography [ECG] hand pads and electroencephalography [EEG] headbands). Additionally, wearable proximity sensors to elicit the social network were deployed among children and their caregivers. Mobile surveys using interactive voice response calls were also used as an additional layer of data collection. An end-line face-to-face survey was conducted at the end of the study. RESULTS: During the implementation, 82 EEG/ECG data entry points were collected across four villages. The sampled children for EEG/ECG were 0 to 5 years old. EEG/ECG data were collected once a week. In every session, children wore the EEG headband for 5 minutes and the ECG hand pad for 3 minutes. In total, 3531 calls were sent over 5 weeks, with 2291 participants picking up the calls and 984 of those answering the consent question. In total, 585 people completed the surveys over the course of 5 weeks. CONCLUSIONS: This study achieved its objective of demonstrating the feasibility of generating data through the unprecedented use of a multimodal approach for tracking child development in Malawi, which is one of the poorest countries in the world. Above and beyond its multiple dimensions, the dynamics of child development are complex. It is the case not only that no data stream in isolation can accurately characterize it, but also that even if combined, infrequent data might miss critical inflection points and interactions between different conditions and behaviors. In turn, combining different modes at a sufficiently high frequency allows researchers to make progress by considering contact patterns, reported symptoms and behaviors, and critical biomarkers all at once. This application showcases that even in developing countries facing multiple constraints, complementary technologies can leverage and accelerate the digitalization of health, bringing benefits to populations that lack new tools for understanding child well-being and development.

Implementation of a Pharmacokinetic Model for Inhaled Anesthetics Into a Software-Based Anesthesia Workstation for LLEAP-Compatible Simulators.

INTRODUCTION: Laerdal Learning Application (LLEAP)-compatible simulation manikins lack some specific functions that can be useful in anesthesia simulation scenarios. Our objective was to develop a software-based anesthesia workstation with a pharmacokinetic model for inhaled anesthetics for this simulation platform. METHODS: A Windows Presentation Foundation application that emulates an Aespire anesthesia workstation was created. The Gas Man simulator (Med Man Simulations) was used as a reference for the pharmacokinetic model. A concordance analysis was made between the results obtained by our model and the reference, in open and semiclosed circuit, in both 70- and 140-kg patients. RESULTS: The mean of the differences between the compartments was less than 0.01 vol% in all circumstances. The percentile rank P2.5 to P97.5 was less than 0.5 vol% in all compartments, except for the open circuit compartment. CONCLUSIONS: No significant differences were found between both pharmacokinetic models. We consider that our software-based anesthesia workstation can be useful for simulating mechanical ventilation and halogenated administration in different scenarios.

On the Electrochemical Detection of Alpha-Fetoprotein Using Aptamers: DNA Isothermal Amplification Strategies to Improve the Performance of Weak Aptamers.

Affinity characterization is essential to develop reliable aptamers for tumor biomarker detection. For alpha-fetoprotein (AFP), a biomarker of hepatocellular carcinoma (HCC), two DNA aptamers were described with very different affinity. In this work, we estimate the dissociation constant of both of them by means of a direct assay on magnetic beads modified with AFP and electrochemical detection on carbon screen-printed electrodes (SPCE). Unlike previous works, both aptamers showed similar dissociation constant (Kd) values, in the subµM range. In order to improve the performance of these aptamers, we proposed the isothermal amplification of the aptamers by both terminal deoxynucleotidyl transferase (TdT) and rolling circle amplification (RCA). Both DNA amplifications improved the sensitivity and also the apparent binding constants from 713 nM to 189 nM for the short aptamer and from 526 nM to 32 nM for the long aptamer. This improvement depends on the true affinity of the binding pair, which ultimately limits the analytical usefulness.

Elucidating Lithium Alloying-Induced Degradation Evolution in High-Capacity Electrodes.

Alloy electrode materials offer high capacity in lithium-ion batteries; however, they exhibit rapid degradation resulting in particle disintegration and electrochemical performance decay. In this study, the evolution of lithium alloying-induced degradation due to electrochemomechanical interactions is examined based on a multipronged electrochemical and microstructural analysis. Copper-tin (Cu6Sn5) is chosen as an exemplary alloy electrode material. Electrodes with compositional variations were fabricated, and electrochemical performance was examined under varying conditions including voltage window, C-rate, and short- and long-term cycling. Morphology and composition analyses of pristine and cycled electrodes were conducted using micrography and spectroscopy techniques. Alloying-induced electrode microstructural evolution was probed using X-ray microtomography. The rapid capacity fading was found to be caused by mechanical degradation of the electrode. Driving the electrode to a lower potential ( E ≈ 0.2 V vs Li/Li+) induced Li-Sn alloy formation and provided the characteristic large capacity; however, this led to a large volume expansion and active particle cracking and disintegration. Copper expulsion was found to be a consequence of the alloy formation; however, it was not the primary contributor to the dramatic electrochemical performance decay.

Pembrolizumab Combined With Either Docetaxel or Gemcitabine in Patients With Advanced or Metastatic Platinum-Refractory Urothelial Cancer: Results From a Phase I Study.

INTRODUCTION: Cytotoxic chemotherapy might prime urothelial cancer (UC) to checkpoint inhibition, prompting a trial of chemotherapy with the programmed death receptor-1 inhibitor pembrolizumab. PATIENTS AND METHODS: Patients with advanced, platinum-refractory UC received pembrolizumab and either docetaxel (arm A) or gemcitabine (arm B). Primary end points were assessments of maximum tolerated dose and dose-limiting toxicity (DLT). Secondary end points were overall response rate (ORR) and progression-free survival (PFS). RESULTS: Twelve patients were enrolled in the initial cohorts; 6 in each arm. One DLT was seen in each arm: Grade 3 hypophosphatemia (arm A), Grade 3 diarrhea (arm B). Adverse events of Grade >3 were observed in 7 (54%), the most common being anemia (6; 50%), fatigue (6; 50%), hyponatremia (4; 33%) and neutropenia (3; 25%), with no treatment-related deaths. There were 5 confirmed responses (1 complete, 4 partial), with an ORR of 42% and disease control rate (DCR) of 58%. Arm A had an ORR of 50% and DCR of 67%, whereas arm B had an ORR of 33% and DCR of 50%. Median PFS was 4.8, 5.7, and 3.7 months for the overall cohort, arm A, and arm B, respectively. CONCLUSION: Pembrolizumab with either docetaxel or gemcitabine is feasible for treatment of platinum-refractory advanced UC patients. Preliminary efficacy was observed. Further examination is warranted.