Sidewall depletion in nano-patterned LAO/STO heterostructures

We report the fabrication of nanostructures from the quasi-two-dimensional electron gas (q2DEG) formed at the LaAlO$_{3}$/ SrTiO$_{3}$ (LAO/STO) interface. The process uses electron beam lithography in combination with reactive ion etching. This technique allows to pattern high-quality structures down to lateral dimensions as small as $100$nm while maintaining the conducting properties without inducing conductivity in the STO substrate. Temperature dependent transport properties of patterned Hall bars of various widths show only a small size dependence of conductivity at low temperature as well as at room temperature. The deviation can be explained by a narrow lateral depletion region. All steps of the patterning process are fully industry compatible.Comment: 5 pages, 4 figure

A kinetic study of mercury(II) transport through a membrane assisted by new transport reagent

Background: A new organodithiophosphorus derivative, namely O-(1,3-Bispiperidino-2-propyl)-4-methoxy phenyldithiophosphonate, was synthesized and then the kinetic behavior of the transport process as a function of concentration, temperature, stirring rate and solvents was investigated.Results: The compound 1 was characterized by elemental analysis, IR, H-1 and P-31 NMR spectroscopies. The transport of mercury(II) ion by a zwitterionic dithiophosphonate 1 in the liquid membrane was studied and the kinetic behavior of the transport process as a function of concentration, temperature, stirring rate and solvents was investigated. The compound 1 is expected to serve as a model liquid membrane transport with mercury(II) ions.Conclusion: A kinetic study of mercury(II) transport through a membrane assisted by O-(1,3-Bispiperidino-2-propyl)4-methoxy phenyldithiophosphonate was performed. It can be concluded that the compound 1 can be provided a general and straightforward route to remove toxic metals ions such as mercury(II) ion from water or other solution

Chondroblastoma of the cuboid with an associated aneurysmal bone cyst: a case report

We report the case of a young adult who presented with a painful foot due to chondroblastoma associated with an aneurismal bone cyst

Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial

Introduction: Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective. Method and analysis: A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process. Ethics and dissemination: Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals. Trial registration number: NCT04131179

Advances in exosome therapies in ophthalmology–From bench to clinical trial

During the last decade, the fields of advanced and personalized therapeutics have been constantly evolving, utilizing novel techniques such as gene editing and RNA therapeutic approaches. However, the method of delivery and tissue specificity remain the main hurdles of these approaches. Exosomes are natural carriers of functional small RNAs and proteins, representing an area of increasing interest in the field of drug delivery. It has been demonstrated that the exosome cargo, especially miRNAs, is at least partially responsible for the therapeutic effects of exosomes. Exosomes deliver their luminal content to the recipient cells and can be used as vesicles for the therapeutic delivery of RNAs and proteins. Synthetic therapeutic drugs can also be encapsulated into exosomes as they have a hydrophilic core, which makes them suitable to carry water-soluble drugs. In addition, engineered exosomes can display a variety of surface molecules, such as peptides, to target specific cells in tissues. The exosome properties present an added advantage to the targeted delivery of therapeutics, leading to increased efficacy and minimizing the adverse side effects. Furthermore, exosomes are natural nanoparticles found in all cell types and as a result, they do not elicit an immune response when administered. Exosomes have also demonstrated decreased long-term accumulation in tissues and organs and thus carry a low risk of systemic toxicity. This review aims to discuss all the advances in exosome therapies in ophthalmology and to give insight into the challenges that would need to be overcome before exosome therapies can be translated into clinical practice

Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: a report of the international immuno-oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Comfort and patient-centred care without excessive sedation:the eCASH concept

We propose an integrated and adaptable approach to improve patient care and clinical outcomes through analgesia and light sedation, initiated early during an episode of critical illness and as a priority of care. This strategy, which may be regarded as an evolution of the Pain, Agitation and Delirium guidelines, is conveyed in the mnemonic eCASH—early Comfort using Analgesia, minimal Sedatives and maximal Humane care. eCASH aims to establish optimal patient comfort with minimal sedation as the default presumption for intensive care unit (ICU) patients in the absence of recognised medical requirements for deeper sedation. Effective pain relief is the first priority for implementation of eCASH: we advocate flexible multimodal analgesia designed to minimise use of opioids. Sedation is secondary to pain relief and where possible should be based on agents that can be titrated to a prespecified target level that is subject to regular review and adjustment; routine use of benzodiazepines should be minimised. From the outset, the objective of sedation strategy is to eliminate the use of sedatives at the earliest medically justifiable opportunity. Effective analgesia and minimal sedation contribute to the larger aims of eCASH by facilitating promotion of sleep, early mobilization strategies and improved communication of patients with staff and relatives, all of which may be expected to assist rehabilitation and avoid isolation, confusion and possible long-term psychological complications of an ICU stay. eCASH represents a new paradigm for patient-centred care in the ICU. Some organizational challenges to the implementation of eCASH are identified.SCOPUS: re.jinfo:eu-repo/semantics/publishe