Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

The TSANZ and Lung Foundation Australia 2023 landscape survey of lung cancer care across Australia and Aotearoa New Zealand.

BACKGROUND AND OBJECTIVE: Unwarranted variations in lung cancer care have been well described in both Australia and Aotearoa New Zealand, with shortfalls in hospital-based workforce and infrastructure previously demonstrated. A survey of lung cancer clinicians was performed to gain an updated understanding of current workforce and infrastructure. METHODS: An online Qualtrics survey included questions on institutional demographics, estimated lung cancer case load, multidisciplinary team (MDT) characteristics including workforce and local infrastructure. We sought to obtain one response from every institution treating lung cancer in Australia and Aotearoa New Zealand. RESULTS: Responses were received from 89 institutions, estimated to include 85% centres treating lung cancer in Australia and 100% of public hospitals in Aotearoa New Zealand. Lung cancer nurse specialist and Nuclear Medicine are poorly represented in multidisciplinary teams (MDTs) with just 34/88 (38%) institutions fulfilling recommended core workforce for MDT meetings. Case presentation is low with 32/88 (36%) regularly discussing all lung cancer patients at MDT. Metropolitan institutions appear to have a more comprehensive range of services on site, compared to non-metropolitan institutions. Few (4/88) institutions have embedded smoking cessation services. Compared to the previous 2021 Landscape Survey, thoracic surgery representation and core MDT workforce have improved, with modest change in specialist nurse numbers. CONCLUSION: This wide-reaching survey has identified persistent deficiencies and variations in lung cancer workforce and gaps in infrastructure. Multidisciplinary collaboration and care coordination are needed to ensure all patients can access timely and equitable lung cancer care.

International standards of care in thoracic oncology: A narrative review of clinical quality indicators.

Unwarranted variations in lung cancer care are widely described. Clinical Quality Indicators (CQIs) enable the systematic identification and alleviation of variations in care and other evidence-practice gaps. The aim of this review was to describe and evaluate lung cancer CQIs utilised internationally, in order to provide a substrate for the development of Australasian lung cancer CQIs and future quality improvement initiatives. A literature search was performed to identify relevant publications; references were excluded if they did not explicitly define original lung cancer-specific quality indicators, or were review or opinion articles. Ultimately, 48 publications containing 661 individual CQIs were evaluated. Although almost all references were published in the last decade, CQIs did not always reflect contemporary standards of care. For example, there were just sixteen CQIs regarding biomarker profiling, eleven CQIs regarding multidisciplinary team review, and three clinical trial enrolment CQIs. Of 307 lung cancer treatment CQIs, almost half (137) pertain to surgical resection; a treatment option available to a minority of lung cancer patients. Consumer engagement during indicator development was uncommon. In conclusion, whilst CQIs are widely measured and reported, they are not always consistent with evidence-based practice, nor do they reliably support the holistic evaluation of the lung cancer care continuum. Moving forward, Australia and New Zealand must adopt a unified, evidence-based and patient-centred approach to drive meaningful improvements in practice.

Quality of acute asthma care: an audit of clinical practice in a Victorian health service.

BACKGROUND: Gaps in the treatment of patients with acute asthma have been repeatedly described in Australia. We conducted a retrospective audit of acute asthma care at a Victorian tertiary institution. AIMS: To describe acute asthma care at a large health network in metropolitan Melbourne, and evaluate the extent to which Emergency Department (ED) care was consistent with National Asthma Council guidelines. METHODS: A retrospective audit was performed of medical records between July 2017 and June 2019. We included adult patients admitted to campuses within the Western Health network in Melbourne, Victoria, where the length of stay was at least 12 h, and the primary discharge diagnosis was asthma. RESULTS: Four hundred and ninety-three admissions were included in the analysis, representing 392 individual patients. Seventy-one percent of patients were female and 27% were current smokers. Ninety-six percent of patients had a prior asthma diagnosis, 63% had a previous hospital presentation and 75% were prescribed an inhaled preventer. In the ED, systemic corticosteroids and inhaled salbutamol were prescribed in 65% and 82% admissions respectively; adjunctive treatments included ipratropium (67% of admissions), magnesium sulfate (30%), adrenaline (11%) and non-invasive ventilation (9%). Overall, ED care was guideline concordant in 59% of admissions. On the wards, treatments prescribed within 24 h of admission included corticosteroids (90% of admissions), salbutamol (84%), ipratropium (64%) and inhaled preventers (63%). The proportion of patients prescribed these treatments, as well as documented follow up (e.g. asthma action plans), varied significantly depending on the treating specialty. CONCLUSION: The emergency treatment of patients with acute asthma frequently deviated from guidelines and there was significant variation in inpatient treatment. Quality improvement initiatives that incorporate structural changes are required to improve asthma care.

Clinical practicality of reporting cutaneous squamous cell carcinoma risk factors at the time of Mohs surgery.

Multiple high-risk factors have been associated with poor outcomes in cutaneous squamous cell carcinoma, including immunosuppression, poor differentiation, depth, diameter, and perineural invasion. While many of these are included in major staging systems, their measurement and reporting vary considerably in clinical practice. We performed a survey study of fellowship-trained Mohs surgeons to explore their attitudes and practices related to recording squamous cell carcinoma high-risk factors and staging information at the time of Mohs. An anonymous Qualtrics survey of 25 questions was distributed to the American College of Mohs Surgery membership listserv. There were 107 complete surveys (response rate 7.1%), with over 95% of subjects from the United States. Fifty-five percent had been practicing 10 years or less, 28% between 11 and 20 years, and the remainder greater than 20 years. Fifty-seven percent were in private or group practices, and 43% were in academia. Nearly all respondents consistently report tumor recurrence (100%), location (100%), immunosuppression (94%), and diameter (93%). Only 70% grade differentiation for every squamous cell carcinoma case. Sixty-six percent of participants consistently record anatomic depth, while only 2% always or almost always record Breslow depth. Although 96% of respondents almost always or always record perineural invasion, only 34% consistently record nerve diameter. Forty-three percent reported that they never or rarely stage cutaneous squamous cell carcinomas, whereas 43% often, almost always, or always stage. In conclusion, certain high-risk factors, such as differentiation, Breslow depth, and stage, are recorded inconsistently by Mohs surgeons. Several participants commented that they prefer to send a central debulk to dermatopathology to assess staging parameters in all tumors with high-risk features. While this strategy may be useful in some practice settings, Mohs surgeons possess the skills necessary to perform a central debulk analysis themselves at the time of Mohs. Whether performed at the time of Mohs or by dermatopathology, assessing high-risk features and accurately staging cutaneous squamous cell carcinoma is paramount to detecting tumors at higher risk of poor outcomes.

Gold nanoparticle design for RNA compaction.

RNA-based therapeutics hold a great promise in treating a variety of diseases. However, double-stranded RNAs (dsRNAs) are inherently unstable, highly charged, and stiff macromolecules that require a delivery vehicle. Cationic ligand functionalized gold nanoparticles (AuNPs) are able to compact nucleic acids and assist in RNA delivery. Here, we use large-scale all-atom molecular dynamics simulations to show that correlations between ligand length, metal core size, and ligand excess free volume control the ability of nanoparticles to bend dsRNA far below its persistence length. The analysis of ammonium binding sites showed that longer ligands that bind deep within the major groove did not cause bending. By limiting ligand length and, thus, excess free volume, we have designed nanoparticles with controlled internal binding to RNA's major groove. NPs that are able to induce RNA bending cause a periodic variation in RNA's major groove width. Density functional theory studies on smaller models support large-scale simulations. Our results are expected to have significant implications in packaging of nucleic acids for their applications in nanotechnology and gene delivery.

Python scripting for biochemistry and molecular biology in Jupyter Notebooks.

A programming workshop has been developed for biochemists and molecular biologists to introduce them to the power and flexibility of solving problems with Python. The workshop is designed to move users beyond a "plug-and-play" approach that is based on spreadsheets and web applications in their teaching and research to writing scripts to parse large collections of data and to perform dynamic calculations. The live-coding workshop is designed to introduce specific coding skills, as well as provide insight into the broader array of open-access resources and libraries that are available for scientific computation.

Hospital-based multidisciplinary lung cancer care in Australia: a survey of the landscape in 2021.

INTRODUCTION: Lung cancer is the leading cause of cancer death in Australia and has the highest cancer burden. Numerous reports describe variations in lung cancer care and outcomes across Australia. There are no data assessing compliance with treatment guidelines and little is known about lung cancer multidisciplinary team (MDT) infrastructure around Australia. METHODS: Clinicians from institutions treating lung cancer were invited to complete an online survey regarding the local infrastructure for lung cancer care and contemporary issues affecting lung cancer. RESULTS: Responses from 79 separate institutions were obtained representing 72% of all known institutions treating lung cancer in Australia. Most (93.6%) held a regular MDT meeting although recommended core membership was only achieved for 42/73 (57.5%) sites. There was no thoracic surgery representation in 17/73 (23.3%) of MDTs and surgery was less represented in regional and low case volume centres. Specialist nurses were present in just 37/79 (46.8%) of all sites. Access to diagnostic and treatment facilities was limited for some institutions. IT infrastructure was variable and most sites (69%) do not perform regular audits against guidelines. The COVID-19 pandemic has driven most sites to incorporate virtual MDT meetings, with variable impact around the country. Clinician support for a national data-driven approach to improving lung cancer care was unanimous. DISCUSSION: This survey demonstrates variations in infrastructure support, provision and membership of lung cancer MDTs, in particular thoracic surgery and specialist lung cancer nurses. This heterogeneity may contribute to some of the well-documented variations in lung cancer outcomes in Australia.

Contraception Utilization in Black Women via a Reproductive Justice Lens.

Background: Over 100 million women make decisions about beginning or resuming contraception after childbirth annually. The burden of an unplanned pregnancy is not equally distributed among racial and ethnic groups in the United States based on the rates of unplanned pregnancies. Objective: This article discusses the disparity in the utilization of contraception among Black women through a reproductive justice lens. Results: The reasons for these differences include a lack of access to care, and differences in contraceptive failure rates among racial and ethnic groups, as well as less of an inclination to have an abortion. Barriers to contraception for breastfeeding persons include patient medical conditions and concerns, and resistance by other health care providers due to language and cultural differences, and knowledge asymmetry. Institutionalized racism, transphobia, and homophobia may compromise patient access to the full spectrum of contraceptive options available. Conclusions: Given the individual and public health benefits of breastfeeding and the impact those benefits can have in helping Black birthing persons and children achieve health equity, it is important for obstetric and pediatric health care providers to play their part in encouraging and supporting breastfeeding.

Dementia Reported Missing: Use of an Online Search Engine to Track Outcomes in Persons With Dementia Reported Missing.

BACKGROUND: Persons with dementia (PWD) reported missing are known to be at high risk for mortality. Analysis of online search engines' reports of missing PWD may show patterns in the data of this relatively common event and the broad patterns relevant to mortality risk factors. METHODS: We searched Google news for PWD reported missing for 2015. Demographics, personal details, and outcomes were recorded. RESULTS: Of 673 cases, 67 were found deceased, 525 alive, and the remainder had unknown outcomes. Mortality did not differ significantly by race/ethnicity for cases with known outcomes, but cases with unknown outcomes were significantly overrepresented among non-Caucasians (P<0.001; analysis of variance). Duration missing predicted mortality (P<0.001; χ(2)), and mortality was lower if a photograph was provided (P<0.05; χ(2)). Five states had no reports and some appeared to have fewer reports that would be expected based on estimates of dementia prevalence. CONCLUSIONS: Duration missing was the strongest predictor of mortality. Likelihood of mortality was not predicted by use of missing person alerts, and this may be a consequence of inconsistent reporting and follow-up of cases across states. Prevalence and mortality may likewise be underestimated because of the variability in usage and reporting of relevant search terms and definitions. Online resources and social media can provide information about trends and outcomes related to missing persons with dementia, but greater consistency is needed in definitions, searching, and reporting.

Perspective: Computational chemistry software and its advancement as illustrated through three grand challenge cases for molecular science.

The field of computational molecular sciences (CMSs) has made innumerable contributions to the understanding of the molecular phenomena that underlie and control chemical processes, which is manifested in a large number of community software projects and codes. The CMS community is now poised to take the next transformative steps of better training in modern software design and engineering methods and tools, increasing interoperability through more systematic adoption of agreed upon standards and accepted best-practices, overcoming unnecessary redundancy in software effort along with greater reproducibility, and increasing the deployment of new software onto hardware platforms from in-house clusters to mid-range computing systems through to modern supercomputers. This in turn will have future impact on the software that will be created to address grand challenge science that we illustrate here: the formulation of diverse catalysts, descriptions of long-range charge and excitation transfer, and development of structural ensembles for intrinsically disordered proteins.

Modifying Provider Practice To Improve Assessment of Unhealthy Weight and Lifestyle in Young Children: Translating Evidence in a Quality Improvement Initiative for At-Risk Children.

BACKGROUND: We designed a quality improvement (QI) project to address the high prevalence of childhood overweight and obesity (OW/OB) in our patient population and the inconsistencies among primary care providers in recognizing and addressing OW/OB. METHODS: We used mixed methods data collection approach to evaluate a QI project, the Childhood Healthy Behaviors Intervention (CHBI), to improve provider obesity prevention practice in two low-income, predominantly African American pediatric primary care clinics. Electronic record data were extracted from all 2-9 year well visits pre- and postintervention for frequency of appropriate diagnostic coding of OW/OB. We reviewed a random sample of records for details of health habit assessment and counseling documentation. Focused interviews were conducted to elicit provider responses regarding impressions of the intervention. RESULTS: The preintervention sample of records (n = 267) was extracted from 18 providers and the postsample (n = 253) from 19 providers. Providers showed improvement in the recognition of OW/OB with appropriate diagnostic coding (52% pre, 68% post), improvement in assessment of health habits informed by the habit survey (0% pre, 76% post), improvement in counseling of healthy behaviors (86% pre, 92% post), and improvement in goal setting of healthy behaviors (12% pre, 70% post). CONCLUSIONS: Our findings suggest that implementing a time efficient primary care intervention with brief provider training can improve provider recognition of OW/OB, as well as improve provider behavior targeted at childhood obesity prevention. This project contributes needed QI evidence on interventions to prevent and address OW/OB in primary care settings and calls for further work to strengthen implementation in similar contexts.

Advances in Molecular Modeling of Nanoparticle-Nucleic Acid Interfaces.

Nanoparticles (NPs) play increasingly important roles in nanotechnology and nanomedicine in which nanoparticle surface chemistry allows for control over interactions with other nanoparticles and biomolecules. In particular, for applications in drug and gene delivery, a fundamental understanding of the NP-nucleic acid interface allows for development of more efficient and effective nanoparticle carriers. Computational modeling can provide insights of processes occurring at the inorganic NP-nucleic interface in detail that is difficult to access by experimental methods. With recent advances such as the use of graphics processing units (GPUs) for simulations, computational modeling has the potential to give unprecedented insight into inorganic-biological interfaces via the examination of increasingly large and complex systems. In this Topical Review, we briefly review computational methods relevant to the interactions of inorganic NPs and nucleic acids and highlight recent insights obtained from various computational methods that were applied to studies of inorganic nanoparticle-nanoparticle and nanoparticle-nucleic acid interfaces.

Binding of single stranded nucleic acids to cationic ligand functionalized gold nanoparticles.

The interactions of nanoparticles (NPs) with single stranded nucleic acids (NAs) have important implications in gene delivery, and nanotechnological and biomedical applications. Here, the complexation of cationic ligand functionalized gold nanoparticles with single stranded deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA) are examined using all atom molecular dynamics simulations. The results indicated that complexation depends mostly on charge of nanoparticle, and, to lesser extent, sequence and type of nucleic acid. For cationic nanoparticles, electrostatic interactions between charged ligands and the nucleic acid backbone dominate binding regardless of nanoparticle charge. Highly charged nanoparticles bind more tightly and cause compaction of the single-stranded NAs through disruption of intrastrand π-π stacking and hydrogen bonding. However, poly-purine strands (polyA-DNA, polyA-RNA) show less change in structure than poly-pyrimidine strands (polyT-DNA, polyU-RNA). Overall, the results show that control over ssNA structure may be achieved with cationic NPs with a charge of more than 30, but the extent of the structural changes depends on sequence.

Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures.

The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy reported for these aptamers during clinical trials, multiple aptamers have been linked using DNA nanostructures. Here, we modify that strategy by linking multiple copies of various thrombin-binding aptamers using DNA weave tiles. The resulting constructs have very high anticoagulant activity in functional assays owing to their improved cooperative binding affinity to thrombin due to optimized spacing, orientation, and the high local concentration of aptamers. We also report the results of molecular dynamics simulations to gain insight into the solution conformations of the tiles. Moreover, by using DNA strand displacement, we were able to turn the coagulation cascade off and on as desired, thereby enabling significantly better control over blood coagulation.

Characterization of Nucleic Acid Compaction with Histone-Mimic Nanoparticles through All-Atom Molecular Dynamics.

The development of nucleic acid (NA) based nanotechnology applications rely on the efficient packaging of DNA and RNA. However, the atomic details of NA-nanoparticle binding remains to be comprehensively characterized. Here, we examined how nanoparticle and solvent properties affect NA compaction. Our large-scale, all-atom simulations of ligand-functionalized gold nanoparticle (NP) binding to double stranded NAs as a function of NP charge and solution salt concentration reveal different responses of RNA and DNA to cationic NPs. We demonstrate that the ability of a nanoparticle to bend DNA is directly correlated with the NPs charge and ligand corona shape, where more than 50% charge neutralization and spherical shape of the NP ligand corona ensured the DNA compaction. However, NP with 100% charge neutralization is needed to bend DNA almost as efficiently as the histone octamer. For RNA in 0.1 M NaCl, even the most highly charged nanoparticles are not capable of causing bending due to charged ligand end groups binding internally to the major groove of RNA. We show that RNA compaction can only be achieved through a combination of highly charged nanoparticles with low salt concentration. Upon interactions with highly charged NPs, DNA bends through periodic variation in groove widths and depths, whereas RNA bends through expansion of the major groove.

Potentially avoidable blood transfusion during trauma resuscitation.

INTRODUCTION: Red blood cell (RBC) transfusion is often essential during trauma resuscitation but is associated with high cost and potential adverse outcomes. This study aimed to determine the incidence of potentially avoidable RBC transfusions (PAT) among adult major trauma patients. MATERIALS AND METHODS: A retrospective review of data collected by Registry on patients presenting between Jan 2006 and Dec 2011 was conducted. Eligible patients received at least 1 unit of RBC in the first 24h following presentation to the Emergency Department (ED). Episodes of PAT were determined according to haemodynamic stability and post-transfusion haemoglobin levels. RESULTS: There were 621 patients included, of whom 224 (36.1%; 95% CI: 32.3-40.0) received PAT. Of them, 132 (58.9%) were haemodynamically stable on arrival and did not require a surgical procedure. Patients with PAT had significantly lower injury severity scores (30 vs 34, p<0.01), higher presenting systolic blood pressure (129 vs 112mm Hg, p<0.01) and a lower frequency of a shock index ≥1 (24.1 vs 65.0%, p<0.01), compared to those without PAT. They also had a significantly lower mortality (13.4 vs 21.7%, p<0.01). CONCLUSIONS: PAT after trauma was common and often delivered to haemodynamically stable patients who did not require surgical procedures. Clinical decision pathways for trauma resuscitation should aim to limit PAT.

Development and validation of green eating behaviors, stage of change, decisional balance, and self-efficacy scales in college students.

OBJECTIVE: To develop and validate an instrument to assess environmentally conscious eating (Green Eating [GE]) behavior (BEH) and GE Transtheoretical Model constructs including Stage of Change (SOC), Decisional Balance (DB), and Self-efficacy (SE). DESIGN: Cross-sectional instrument development survey. SETTING/PARTICIPANTS: Convenience sample (n = 954) of 18- to 24-year-old college students from a northeastern university. ANALYSIS: The sample was randomly split: (N1) and (N2). N1 was used for exploratory factor analyses using principal components analyses; N2 was used for confirmatory analyses (structural modeling) and reliability analyses (coefficient α). The full sample was used for measurement invariance (multi-group confirmatory analyses) and convergent validity (BEH) and known group validation (DB and SE) by SOC using analysis of variance. RESULTS: Reliable (α > .7), psychometrically sound, and stable measures included 2 correlated 5-item DB subscales (Pros and Cons), 2 correlated SE subscales (school [5 items] and home [3 items]), and a single 6-item BEH scale. Most students (66%) were in Precontemplation and Contemplation SOC. Behavior, DB, and SE scales differed significantly by SOC (P < .001) with moderate to large effect sizes, as predicted by the Transtheoretical Model, which supported the validity of these measures. CONCLUSIONS AND IMPLICATIONS: Successful development and preliminary validation of this 25-item GE instrument provides a basis for assessment as well as development of tailored interventions for college students.

Chlamydia detection during the menstrual cycle: a cross-sectional study of women attending a sexual health service.

BACKGROUND: We investigated the detection of chlamydia at different stages of the menstrual cycle. METHODS: Electronic medical records for women attending Melbourne Sexual Health Centre between March 2011 and 31(st) December 2012, who were tested for chlamydia by nucleic acid amplification of high vaginal, cervical, or urinary samples, and who recorded a date of last normal menstrual period (LNMP) between 0-28 days were included in the analysis. Logistic regression was used to calculate adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the association of chlamydia with menstrual cycle adjusted by demographics and behavioural variables. Chlamydia and beta globin load were determined on those with stored samples. RESULTS: Of the 10,017 consultations that included a test for chlamydia and a valid LNMP, there were 417 in which chlamydia was detected. The proportion of samples with chlamydia was greater in the luteal phase (4.8%, 184/3831) than in the follicular phase (3.4%, 233/6816) both in the crude (OR 1.29 95%CI 1.1-1.6, p = 0.01) and adjusted odds ratio (aOR) 1.4 (95%CI 1.1-1.8, p = 0.004). Among women using hormonal contraception, there was no significant association with the luteal phase of the menstrual cycle (aOR 1.3, 95%CI 0.9, 1.8, p = 0.18). Among women not using hormonal contraception, there was a significant association with the luteal phase (aOR 1.6, (95% CI 1.1-2.3, p = 0.007). The chlamydia load was not significantly different in the 329 positive stored samples in weeks 3 and 4 vs weeks 1 and 2 for any site (P>0.12). CONCLUSIONS: The higher detection of chlamydia detection in the luteal phase of the menstrual cycle in only those not taking hormonal contraception suggest that hormonal factors influence chlamydia detection. The absence of a significantly highly chlamydia load in women during the luteal phase raises questions about the mechanism.