Patient journey and timeliness of care for patients with breast cancer in Africa: a scoping review protocol.

INTRODUCTION: Cancer is the leading cause of death worldwide, with breast cancer being one of the most commonly diagnosed types. Low-income and middle-income countries account for nearly half of all breast cancer cases and related fatalities. In Africa, mortality rates are higher and survival rates are lower compared with developed countries. Timeliness of care is a critical aspect of healthcare, but various studies and healthcare systems use different criteria and methods to measure it. Assessing the breast cancer care pathway and understanding the determinants of delayed care are essential for effective interventions. Therefore, this scoping review aims to evaluate the methods used to measure the timeliness of breast cancer care, identify specific points in the care pathway where delays are most frequently reported, and examine the factors affecting the timeliness of breast cancer care in Africa. METHODS AND ANALYSIS: We will conduct this scoping review using the Arksey and O'Malley framework endorsed by the Joanna Briggs Institute. A scoping review of articles written in English concerning the timeliness of breast cancer care in the African context will be undertaken. Six electronic databases (MEDLINE, EMBASE, CINAHL, SCOPUS, WEB Of SCIENCE and PsycINFO) will be searched to identify published literature on timeliness of breast care in Africa. Two reviewers will independently screen the articles at both the abstract and full-text stages, guided by predetermined inclusion and exclusion criteria. The full texts of identified studies will be further examined and charted using a data extraction form guided by the Model of Pathways to Treatment framework. Publications describing the time to diagnosis and its associated factors in the contexts of breast cancer will be considered for inclusion, with no restrictions based on date of publication. Studies that are published in languages other than English and that do not focus on the timeliness of care or time-related aspects within the care pathway will be excluded. Evidence will be narratively synthesised and analysed. ETHICS AND DISSEMINATION: Ethical approval is not needed as this scoping review does not involve collecting data from human participants. The results produced from this review will be submitted to a scientific peer-reviewed journal for publication and will be presented at scientific meetings.

Optical fibre based artificial compound eyes for direct static imaging and ultrafast motion detection.

Natural selection has driven arthropods to evolve fantastic natural compound eyes (NCEs) with a unique anatomical structure, providing a promising blueprint for artificial compound eyes (ACEs) to achieve static and dynamic perceptions in complex environments. Specifically, each NCE utilises an array of ommatidia, the imaging units, distributed on a curved surface to enable abundant merits. This has inspired the development of many ACEs using various microlens arrays, but the reported ACEs have limited performances in static imaging and motion detection. Particularly, it is challenging to mimic the apposition modality to effectively transmit light rays collected by many microlenses on a curved surface to a flat imaging sensor chip while preserving their spatial relationships without interference. In this study, we integrate 271 lensed polymer optical fibres into a dome-like structure to faithfully mimic the structure of NCE. Our ACE has several parameters comparable to the NCEs: 271 ommatidia versus 272 for bark beetles, and 180o field of view (FOV) versus 150-180o FOV for most arthropods. In addition, our ACE outperforms the typical NCEs by ~100 times in dynamic response: 31.3 kHz versus 205 Hz for Glossina morsitans. Compared with other reported ACEs, our ACE enables real-time, 180o panoramic direct imaging and depth estimation within its nearly infinite depth of field. Moreover, our ACE can respond to an angular motion up to 5.6×106 deg/s with the ability to identify translation and rotation, making it suitable for applications to capture high-speed objects, such as surveillance, unmanned aerial/ground vehicles, and virtual reality.

Neural Basis of Pain Empathy Dysregulations in Mental Disorders - A Pre-registered Neuroimaging Meta-Analysis.

BACKGROUND: Pain empathy represents a fundamental building block of several social functions, which have been demonstrated to be impaired across various mental disorders by accumulating evidence from case-control functional magnetic resonance imaging (fMRI) studies. However, it remains unclear whether the dysregulations are underpinned by robust neural alterations across mental disorders. METHODS: This study utilized coordinate-based meta-analyses to quantitatively determine robust markers of altered pain empathy across mental disorders. To support the interpretation of the findings exploratory network-level and behavioral meta-analyses were conducted. RESULTS: Quantitative analysis of eleven case-control fMRI studies with data from 296 patients and 229 controls revealed patients with mental disorders exhibited increased pain empathic reactivity in the left anterior cingulate gyrus, adjacent medial prefrontal cortex, and right middle temporal gyrus, yet decreased activity in the left cerebellum IV/V and left middle occipital gyrus compared to controls. The hyperactive regions showed network-level interactions with the core default mode network (DMN) and were associated with affective and social cognitive domains. CONCLUSIONS: The findings suggest that pain-empathic alterations across mental disorders are underpinned by excessive empathic reactivity in brain systems involved in empathic distress and social processes, highlighting a shared therapeutic target to normalize basal social dysfunctions in mental disorders.

Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients.

PURPOSE: Clinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients' characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs. METHODS: Patients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as "Contraindicated," "Avoid Concomitant Use," or "Other DDIs" (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being "Contraindicated" to receive nirmatrelvir/ritonavir. FINDINGS: Of the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as "Contraindicated" (11%) and/or "Avoid Concomitant Use" (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as "Contraindicated" when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19. IMPLICATIONS: A significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications that are "Contraindicated" with nirmatrelvir/ritonavir. In the evolving COVID-19 era, these findings provide insights into patients hospitalized for COVID-19, and the polypharmacy evaluations that clinicians may encounter when selecting among DAAs to manage COVID-19.

Site-selective α-C(sp3)-H arylation of dialkylamines via hydrogen atom transfer catalysis-enabled radical aryl migration.

Site-selective C(sp3)-H arylation is an appealing strategy to synthesize complex arene structures but remains a challenge facing synthetic chemists. Here we report the use of photoredox-mediated hydrogen atom transfer (HAT) catalysis to accomplish the site-selective α-C(sp3)-H arylation of dialkylamine-derived ureas through 1,4-radical aryl migration, by which a wide array of benzylamine motifs can be incorporated to the medicinally relevant systems in the late-stage installation steps. In contrast to previous efforts, this C-H arylation protocol exhibits specific site-selectivity, proforming predominantly on sterically more-hindered secondary and tertiary α-amino carbon centers, while the C-H functionalization of sterically less-hindered N-methyl group can be effectively circumvented in most cases. Moreover, a diverse range of multi-substituted piperidine derivatives can be obtained with excellent diastereoselectivity. Mechanistic and computational studies demonstrate that the rate-determining step for methylene C-H arylation is the initial H atom abstraction, whereas the radical ipso cyclization step bears the highest energy barrier for N-methyl functionalization. The relatively lower activation free energies for secondary and tertiary α-amino C-H arylation compared with the functionalization of methylic C-H bond lead to the exceptional site-selectivity.

PVA-assisted spray deposited porous Li4Ti5O12 thin film as high-rate and long-cycle anode for lithium-ion thin-film batteries.

Spinel Li4Ti5O12 (LTO), a zero-strain material, is a promising anode material for solid-state thin-film lithium-ion batteries (TFB). However, the preparation of high-performance Li4Ti5O12 thin-film electrodes through facile methods remains a significant challenge. Herein, we present a novel approach to prepare a binder- and conductor-free porous Li4Ti5O12 (P-LTO) thin-film. This approach polyvinyl alcohol (PVA)-assisted spray deposition and does not require the use of complex or expensive methods. Adding PVA to the precursor solution effectively prevents thin-film cracking during high-temperature annealing, enhances adhesion, and forms a highly interconnected porous structure. This unique structure shortens the lithium-ion diffusion pathways and facilitates electron transport. Therefore, P-LTO thin film electrodes demonstrate exceptional rate capacity of 104.1 mAh/g at a current density of 100C. In addition, the electrodes exhibit ultra-long cycle stability, retaining 80.9 % capacity after 10,000 cycles at 10C. This work offers a novel approach for the preparation of high-performance thin-film electrodes for TFBs.

Accessing supports due to others' harmful drinking.

INTRODUCTION: Alcohol's harm to others (AHTO) refers to harms caused to those other than the drinker. The current paper estimates the prevalence of formal and informal supports sought due to AHTO and examines whether the type of support accessed varies by sociodemographic, economic and harm-related characteristics. METHODS: An Australian sample of 2574 people completed the 2021 AHTO survey, out of which 888 perceived they experienced harm from another's drinking. Prevalence of accessing services and supports was measured. Additionally, several sociodemographic factors, economic factors and harm-related factors were included in multivariable logistic regression models predicting service/support use. Specifically, four models were constructed probing use of any service/support, use of police, use of counselling services and use of family/friend support. RESULTS: Of the survey sample, 12.4% accessed any support/service. Seeking support from family and/or friends was most common, followed by police, counselling, healthcare services and being admitted to hospital. Women had higher odds of accessing counselling and family/friend support. Respondents with a higher education level and two or more financial stressors had higher odds of accessing police and counselling. Respondents harmed by a stranger had higher odds of accessing police, whereas respondents harmed by someone they know had higher odds of seeking support from family/friends. Experiencing more severe harm was associated with greater odds of accessing any support. DISCUSSION AND CONCLUSIONS: Several sociodemographic and economic factors were associated with accessing different supports. These findings may inform service development, interventions and policy changes for people affected by others' drinking.

Enhancing the Structural Stability and Electrochemical Performance of High-Nickel Cathode Materials through Ti Doping with an Exothermic Non-oxide Precursor.

The foreseeable global cobalt (Co) crisis has driven the demand for cathode materials with less Co dependence, where high-nickel layered oxides are a promising solution due to their high energy density and low cost. However, these materials suffer from poor cycling stability and rapid voltage decay due to lattice displacement and nanostrain accumulation. Here, we introduced an exothermic TiN dopant via a scalable coating method to stabilize LiNi0.917Co0.056Mn0.026O2 (NCM92) materials. The exothermic reaction of TiN conversion generates extra heat during the calcination process on the cathode surface, promotes the lithiation process, and tunes the morphology of the cathode material, resulting in compact and conformal smaller particle sizes to provide better particle integration and lithium diffusion coefficient. Moreover, the Ti dopant substitutes the Ni3+ site to generate stronger Ti-O bonding, leading to higher structural stability and extended cycle life. The Ti-doped NCM (NCM92_TiN) shows a remarkable cycling stability of maintaining 80% capacity retention for 400 cycles, while bare NCM92 can only reach 88 cycles. Furthermore, the NCM92_TiN cathodes demonstrate an enhanced rate capability and achieve a discharge capacity of over 168 mAh g-1 at 5C.

Primary cilia mediate skeletogenic BMP and Hedgehog signaling in heterotopic ossification.

Heterotopic ossification (HO), defined as the formation of extraskeletal bone in muscle and soft tissues, is a diverse pathological process caused by either genetic mutations or inciting trauma. Fibrodysplasia ossificans progressiva (FOP) is a genetic form of HO caused by mutations in the bone morphogenetic protein (BMP) type I receptor gene activin A receptor type 1 (ACVR1). These mutations make ACVR1 hypersensitive to BMP and responsive to activin A. Hedgehog (Hh) signaling also contributes to HO development. However, the exact pathophysiology of how skeletogenic cells contribute to endochondral ossification in FOP remains unknown. Here, we showed that the wild-type or FOP-mutant ACVR1 localized in the cilia of stem cells from human exfoliated deciduous teeth with key FOP signaling components, including activin A receptor type 2A/2B, SMAD family member 1/5, and FK506-binding protein 12kD. Cilia suppression by deletion of intraflagellar transport 88 or ADP ribosylation factor like GTPase 3 effectively inhibited pathological BMP and Hh signaling, subdued aberrant chondro-osteogenic differentiation in primary mouse or human FOP cells, and diminished in vivo extraskeletal ossification in Acvr1Q207D, Sox2-Cre; Acvr1R206H/+ FOP mice and in burn tenotomy-treated wild-type mice. Our results provide a rationale for early and localized suppression of cilia in affected tissues after injury as a therapeutic strategy against either genetic or acquired HO.

Multiple stress fractures: A case report and discussion.

Stress fracture is the result of bone destruction with prolonged and repetitive loading. It usually occurs among various groups, including athletes, military recruits, and others. Early stress fractures often undergo undiagnosed or misdiagnosed because of atypical symptoms and effective medical examination. Here, we report a rare clinical case about the multiple stress fractures in one adolescent. Expect for the pathological biopsy, it hardly gets confirm diagnosis. With the increasing population of sports lover, healthcare institutions should be enhanced their understanding of stress fractures and enable effective management at an early stage.

Pathologic Complete Response to Neoadjuvant Chemotherapy and Pembrolizumab in Postpartum High-Risk Basal-Type Breast Cancer.

Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.

Research trends and hotspots of myositis ossificans: a bibliometric analysis from 1993 to 2022.

Myositis ossificans (MO) is characterized by benign heterotopic ossificans in soft tissues like muscles, which can be classified into nonhereditary MO and fibrodysplasia ossificans progressiva (FOP). Although MO has been studied for decades, no research reviewed and analyzed the features of publications in this field quantitatively and qualitatively. Using bibliometrics tools (bibliometrix R package, VOSviewer, and CiteSpace), we conducted a bibliometric analysis of 1280 articles regarding MO in the Web of Science Core Collection database from 1993 to 2022. The annual number of publications and related research areas in the MO field increased gradually in the past 20 years. The USA contributed the most percentage (42.58%) of articles. The University of Pennsylvania (UPenn) and the Journal Bone published the most articles among all institutions and journals. Kaplan FS and Shore EM from UPenn were the top two scholars who made the largest contributions to this field. Keyword analysis showed that research hotspots changed from traumatic MO and clinical management of MO to the genetic etiology, pathogenesis, and treatment of FOP. This study can provide new insights into the research trends of MO and helps researchers grasp and determine future study directions more easily.

A Simplified GBR Treatment and Evaluation of Posterior Seibert Class I Ridge Defects via Bio-collagen and Platelet-Rich Fibrin: A Retrospective Study.

BACKGROUND: Classical guided bone regeneration (GBR) treatments can achieve favorable clinical results for ridge defects. However, extensive bone augmentation in the non-esthetic area in the posterior region for minor ridge defects is unnecessary. Therefore, this study used a collagen and Platelet-rich fibrin (PRF) mixture for bone augmentation on minor posterior ridge defects and evaluated the effects. METHODS: 22 Seibert Class I ridge defects were treated with BC and covered with a PRF membrane (simplified guided bone regeneration, simplified GBR) and other 22 were treated with Bio-Oss and covered with Bio-Gide (classical GBR). Cone-beam computed tomography imaging was conducted 6 months post-surgery to compare the ridge's horizontal width (HW) and buccal ridge's horizontal width to assess the osteogenic effect. In addition, the buccal ridge contour morphology was studied and classified. RESULTS: The buccal ridge contour of simplified GBR was Type A in 14 cases, Type B in 7 cases, and Type C in 1 case and it of classical GBR was Type A in 11 cases, Type B in 8 cases, and Type C in 3 cases. The mean HW significantly increased by 1.50 mm of simplified GBR treatment, while it increased by 1.83 mm in classical GBR treatment. CONCLUSION: The combined use of BC and PRF had a significant effect on bone augmentation and this treatment exhibited promising clinical results for correcting posterior Seibert Class I ridge defects. The morphological classification of the reconstructive effect in this study can be utilized in future clinical work.

Modelling the impacts of volumetric and minimum unit pricing for alcohol on social harms in Australia.

AIMS: Alcohol pricing policies may reduce alcohol-related harms, yet little work has been done to model their effectiveness beyond health outcomes especially in Australia. We aim to estimate the impacts of four taxation and minimum unit pricing (MUP) interventions on selected social harms across sex and age subgroups in Australia. METHODS: We used econometrics and epidemiologic simulations using demand elasticity and risk measures. We modelled four policies including (A) uniform excise rates (UER) (based on alcohol units) (B) MUP $1.30 on all alcoholic beverages (C) UER + 10 % (D) MUP$ 1.50. People who consumed alcohol were classified as (a) moderate (≤ 14 Australian standard drinks (SDs) per week) (b) Hazardous (15-42 SDs per week for men and 14-35 ASDs for women) and (c) Harmful (> 42 SDs per week for men and > 35 ASDs for women). Outcomes were sickness absence, sickness presenteeism, unemployment, antisocial behaviours, and police-reported crimes. We used relative risk functions from meta-analysis, cohort study, cross-sectional survey, or attributable fractions from routine criminal records. We applied the potential impact fraction to estimate the reduction in social harms by age group and sex after implementation of pricing policies. RESULTS: All four modelled pricing policies resulted in a decrease in the overall mean baseline of current alcohol consumption, primarily due to fewer people drinking harmful amounts. These policies also reduced the total number of crimes and workplace harms compared to the current taxation system. These reductions were consistent across all age and sex subgroups. Specifically, sickness absence decreased by 0.2-0.4 %, alcohol-related sickness presenteeism by 7-9 %, unemployment by 0.5-0.7 %, alcohol-related antisocial behaviours by 7.3-11.1 %, and crimes by 4-6 %. Of all the policies, the implementation of a $1.50 MUP resulted in the largest reductions across most outcome measures. CONCLUSION: Our results highlight that alcohol pricing policies can address the burden of social harms in Australia. However, pricing policies should just form part of a comprehensive alcohol policy approach along with other proven policy measures such as bans on aggressive marketing of alcoholic products and enforcing the restrictions on the availability of alcohol through outlet density regulation or reduced hours of sale to have a more impact on social harms.

Adverse Effects of Opioid Analgesics in Osteoarthritis Treatment: A Global Meta-Analysis, 2000-2022.

Osteoarthritis (OA) treatment commonly depends on nonsteroidal anti-inflammatory drugs and opioid medications. Nevertheless, the clinical use of opioids is controversial due to their adverse effects and addiction potential. This study, drawing on 24 randomized controlled trials (RCTs) with a total of 9,586 patients, thoroughly explored the various side effects associated with opioid use in OA treatment. The results provide additional insight into the non-addictive risks of opioids and may assist clinicians in their judicious use, potentially fostering the advancement of safer treatment options. By reducing the risks of misuse and addiction, public health and safety can be enhanced.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Background: Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Method: Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Results: Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Conclusions: Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia in France.

OBJECTIVE: To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia (TDT) in France. METHODS: We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of ß-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data. Patients were excluded if medical records showed evidence of sickle cell disease, α-thalassemia, hereditary persistence of fetal hemoglobin, or hematopoietic stem cell transplant. Clinical complications, mortality, treatment use, and healthcare resource utilization were evaluated. RESULTS: Overall, 331 eligible patients with TDT were identified. Mean age was 26.1 (standard deviation [SD]: 18.0) years, and 50.5% were male. Common clinical complications were endocrine (26.0%), hepatobiliary (22.7%), and cardiopulmonary (18.7%). Fifteen (4.5%) patients died during follow-up, with a mortality rate of 1.16 deaths per 100 person-years (mean age of death: 52.5 years [SD: 22]). Patients had a mean of 13.5 (SD: 5.2) RBC transfusion episodes and 11.2 (SD: 5.3) iron chelation therapy treatments per year. Healthcare resource utilization was substantial, with a mean of 14.8 inpatient hospitalizations (including 13.8 mean inpatient day cases) and 16.9 outpatient prescriptions per patient per year. CONCLUSIONS: Patients with TDT in France experience significant clinical complications, elevated mortality, and substantial healthcare resource utilization driven by frequent RBC transfusion episodes and inpatient hospitalizations. These results reinforce the need for disease-modifying therapies for this patient population.

Harm from the drinking of people you know: A range of effects from different relationships.

AIMS: To describe the range of effects experienced due to the drinking of people respondents know and analyze risk and protective factors for harm from the drinking of partners and household members, other relatives and friends and co-workers. DESIGN, SETTING AND PARTICIPANTS: Surveys of 2574 participants' experiences were obtained from two samples: 1000 people responded to random digitally dialled Australian mobile calls and 1574 participants responded from the Life in AustraliaTM panel survey. MEASUREMENTS: Respondents were asked whether they had been negatively affected in the previous 12 months by the drinking of persons they knew who were 'a heavy drinker or drank a lot sometimes' and the nature of these harms. Weighted logistic regressions were used to analyze differences in rates of key negative outcomes from known others' drinking by gender, age and socio-economic status. FINDINGS: Almost two thirds [60.2%; 95% confidence interval (CI) = 57.7%-62.7%] of participants reported having heavy drinkers in their lives and 21.8% (95% CI = 19.8%-23.9%) reported being negatively affected by the drinking of people they knew well in some way. Participants reported a gamut of effects, including, most commonly, adverse social effects: having to transport relatives and friends who had been drinking, role failure and faults, being emotionally hurt or neglected, serious arguments, family problems, having to care for drinkers and verbal abuse. Less commonly, respondents reported physical or sexual harm, property damage, financial stress and threats from others' drinking. Women (odds ratio = 1.49; 95% CI = 1.13-1.95), younger people, rural, Australian-born (vs. respondents born overseas in non-English speaking countries) and more frequent drinkers were more likely to report harm from a drinker they knew than their counterparts after adjusting for other variables in the model. CONCLUSIONS: Australians appear to be commonly adversely affected by the drinking of people they know. Harms from known drinkers are more likely to be experienced by women than men, particularly from the people they live with and other relatives.

Surface-Enhanced Raman Spectroscopy-Based Detection of EMT-Related Targets in Endometrial Cancer: Potential for Diagnosis and Prognostic Prediction.

Epithelial-mesenchymal transformation (EMT) is one of the important mechanisms of malignancy in endometrial cancer, and detection of EMT targets is a key challenge to explore the mechanism of endometrial carcinoma (EC) malignancy and discover novel therapeutic targets. This study attempts to use surface-enhanced Raman spectroscopy (SERS), a highly sensitive, ultrafast, and highly specific analytical technology, to rapidly detect microRNA-200a-3p and ZEB1 in endometrial cancer cell lines. The silver nanoparticles were decorated with iodine and calcium ions, can capture the SERS fingerprints of microRNA-200a-3p and ZEB1 protein, and effectively avoid the interference of impurity signals. At the same time, the method has high sensitivity for the detection of the above EMT targets, and the lowest detection limits for microRNA-200a-3p and ZEB1 are 4.5 pmol/mL and 10 ng/mL, respectively. At the lowest detection concentration, the method still has high stability. In addition, principal component analysis can not only identify microRNA-200a-3p and ZEB1 protein from a variety of EMT-associated microRNA and proteins but also identify them in the total RNA and total protein of endometrial cancer cell lines and normal endometrial epithelial cell lines. This study modified silver nanoparticles with iodine and calcium ions and for the first time captured the fingerprints of EMT-related targets microRNA-200a-3p and ZEB1 at the same time without label, and the method has high sensitivity and stability. This SERS-based method has immense potential for elucidating the molecular mechanisms of EMT-related EC, as well as identifying biomarkers for malignant degree and prognosis prediction.