Social determinants of health inequalities in early phase clinical trials in Northern England.

BACKGROUND: Early phase clinical trials in Oncology represent a subspecialised area where UK patient selection is influenced by access to Experimental Cancer Medicine Centres (ECMCs). Equity of access with respect to social determinants of health (SDoH) were explored for two major ECMCs. METHODS: A retrospective cohort study including all referrals to Newcastle and Manchester ECMCs in 2021 was completed. Consent to screening or pre-screening was stratified against SDoH characteristics, including: Index of Multiple Deprivation (IMD) decile, ethnicity and distance to centre. RESULTS: 1243 patients were referred for trials. IMD quintile 1 (most deprived) patients had reduced likelihood of referral compared to expected population models (OR, 0.67; 95% CI: 0.55 to 0.80, p = <0.0001). IMD quintile 5 (least deprived) had increased likelihood of referral (OR, 1.46; 95% CI: 1.17 to 1.82, p = 0.0007). Living beyond median distance from Manchester reduced the likelihood of consenting to trials (OR, 0.72; 95% CI: 0.55 to 0.94, p = 0.015). Ethnicity data represented a White British propensity. CONCLUSIONS: Inequalities in socioeconomic and geographic factors influence referral and enrolment to early phase clinical trials in Northern England. This has implications for equity of access and generalisability of trial results internationally and warrants further study.

Role of misalignment-induced angular chirp in the electro-optic detection of THz waves.

A general description of electro-optic detection including non-collinear phase matching and finite transverse beam profiles is presented. It is shown theoretically and experimentally that non-collinear phase matching in ZnTe (and similar materials) produces an angular chirp in the χ(2)-generated optical signal. Due to this, in non-collinear THz and probe arrangements such as single-shot THz measurements or through accidental misalignment, measurement of an undistorted THz signal is critically dependent on having sufficient angular acceptance in the optical probe path. The associated spatial walk-off can also preclude the phase retardation approximation used in THz-TDS. The rate of misalignment-induced chirping in commonly used ZnTe and GaP schemes is tabulated, allowing ready analysis of a detection system.

EPIC: an evaluation of the psychological impact of early-phase clinical trials in cancer patients.

BACKGROUND: Anxiety and depression in patients with cancer is associated with decreased quality of life and increased morbidity and mortality. However, these are often overlooked and untreated. Early-phase clinical trials (EPCTs) recruit patients with advanced cancers who frequently lack future treatment options, which may lead to increased anxiety and depression. Despite this, EPCTs do not routinely consider psychological screening for patients. PATIENTS AND METHODS: This prospective observational study explored levels of anxiety and depression alongside impact of trial participation in the context of EPCTs. The Hospital Anxiety and Depression Scale and the Brief Illness Perceptions Questionnaire were completed at the point of EPCT consent, the end of screening and at pre-specified time points thereafter. RESULTS: Sixty-four patients (median age 56 years; median Eastern Cooperative Oncology Group performance status 1) were recruited. At consent, 57 patients returned questionnaires; 39% reported clinically relevant levels of anxiety whilst 18% reported clinically relevant levels of depression. Sixty-three percent of patients experiencing psychological distress had never previously reported this. Males were more likely to be depressed (P = 0.037) and females were more likely to be anxious (P = 0.011). Changes in anxiety or depression were observed after trial enrolment on an individual level, but not significant on a population level. CONCLUSIONS: Patients on EPCTs are at an increased risk of anxiety and depression but may not seek relevant support. Sites offering EPCTs should consider including psychological screening to encourage a more holistic approach to cancer care and consider the sex of individuals when tailoring psychological support to meet specific needs.

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer.

INTRODUCTION: MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). METHODS: A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. RESULTS: Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months-NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1-mutated patients, the ORR was 42.8%. CONCLUSION: The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

Publisher Correction: Impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of c-plane GaN/AlGaN quantum wells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A randomized trial of the electronic Lung Cancer Symptom Scale for quality-of-life assessment in patients with advanced non-small-cell lung cancer.

Introduction: Improving health-related quality of life (hrqol) is a key goal of systemic therapy in advanced lung cancer, although routine assessment remains challenging. We analyzed the impact of a real-time electronic hrqol tool, the electronic Lung Cancer Symptom Scale (elcss-ql), on palliative care (pc) referral rates, patterns of chemotherapy treatment, and use of other supportive interventions in patients with advanced non-small-cell lung cancer (nsclc) receiving first-line chemotherapy. Methods: Patients with advanced nsclc starting first-line chemotherapy were randomized to their oncologist receiving or not receiving their elcss-ql data before each clinic visit. Patients completed the elcss-ql at baseline, before each chemotherapy cycle, and at subsequent follow-up visits until disease progression. Prospective data about the pc referral rate, hrqol, and use of other supportive interventions were collected. Results: For the 95 patients with advanced nsclc who participated, oncologists received real-time elcss-ql data for 44 (elcss-ql arm) and standard clinical assessment alone for 51 (standard arm). The primary endpoint, the pc referral rate, was numerically higher, but statistically similar, for patients in the elcss-ql and standard arms. The hrqol scores over time were not significantly different between the two study arms. Conclusions: The elcss-ql is feasible as a tool for use in routine clinical practice, although no statistically significant effect of its use was demonstrated in our study. Improving access to supportive care through the collection of patient-reported outcomes and hrqol should be an important component of care for patients with advanced lung cancer.

Impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of c-plane GaN/AlGaN quantum wells.

We report on a combined theoretical and experimental study of the impact of alloy fluctuations and Coulomb effects on the electronic and optical properties of [Formula: see text]-plane GaN/AlGaN multi-quantum well systems. The presence of carrier localization effects in this system was demonstrated by experimental observations, such as the "S-shape" temperature dependence of the photoluminescence (PL) peak energy, and non-exponential PL decay curves that varied across the PL spectra at 10 K. A three-dimensional modified continuum model, coupled with a self-consistent Hartree scheme, was employed to gain insight into the electronic and optical properties of the experimentally studied [Formula: see text]-plane GaN/AlGaN quantum wells. This model confirmed the existence of strong hole localization arising from the combined effects of the built-in polarization field along the growth direction and the alloy fluctuations at the quantum well/barrier interface. However, for electrons these localization effects are less pronounced in comparison to the holes. Furthermore, our calculations show that the attractive Coulomb interaction between electron and hole results in exciton localization. This behavior is in contrast to the picture of independently localized electrons and holes, often used to explain the radiative recombination process in [Formula: see text]-plane InGaN/GaN quantum well systems.

Author Correction: Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration.

The original version of this Article contained an error in the abstract, referring to "multi-megawatt-per-metre" instead of "multi-megavolt-per-metre". This has now been corrected in both the PDF and HTML versions of the Article.

Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration.

The sub-luminal phase velocity of electromagnetic waves in free space is generally unobtainable, being closely linked to forbidden faster than light group velocities. The requirement of sub-luminal phase-velocity in laser-driven particle acceleration schemes imposes a limit on the total acceleration achievable in free space, and necessitates the use of dispersive structures or waveguides for extending the field-particle interaction. We demonstrate a travelling source approach that overcomes the sub-luminal propagation limits. The approach exploits ultrafast optical sources with slow group velocity propagation, and a group-to-phase front conversion through nonlinear optical interaction. The concept is demonstrated with two terahertz generation processes, nonlinear optical rectification and current-surge rectification. We report measurements of longitudinally polarised single-cycle electric fields with phase and group velocity between 0.77c and 1.75c. The ability to scale to multi-megavolt-per-metre field strengths is demonstrated. Our approach paves the way towards the realisation of cheap and compact particle accelerators with femtosecond scale control of particles.Controlled generation of terahertz radiation with subluminal phase velocities is a key issue in laser-driven particle acceleration. Here, the authors demonstrate a travelling-source approach utilizing the group-to-phase front conversion to overcome the sub-luminal propagation limit.

Is chemotherapy always required for cancer in pregnancy? An observational study.

BACKGROUND: Cancer in pregnancy is relatively rare, but the incidence is increasing. Several studies show that cytotoxic agents are safe to use in pregnancy from the second trimester onwards. AIMS: This study assesses the maternal and foetal outcomes of cancers diagnosed during pregnancy. In particular, it focuses on a subset of women who elected to defer systemic chemotherapy until after delivery. This study examines if all cancers need to be treated during pregnancy or if, in certain cases, treatment can be safely deferred until after full-term delivery. METHODS: This is a retrospective observational study of women diagnosed with cancer during pregnancy in an Irish cancer centre over a 27-year period. All women diagnosed with cancer during pregnancy who were referred to the medical oncology department for consideration of chemotherapy were included in this study. Medical and pharmacy records were extensively reviewed. RESULTS: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology for consideration of systemic chemotherapy. Sixteen women (64%) commenced chemotherapy during pregnancy, seven women (28%) did not receive chemotherapy while pregnant, but commenced treatment immediately after delivery, and two (8%) did not receive any systemic chemotherapy at all. Of the seven women who commenced chemotherapy after delivery, six (85.7%) were diagnosed before 30/40 gestation. There were three cases of Hodgkin's lymphoma, two breast cancers and one ovarian cancer. After a median follow-up of 12 years, all six mothers remain disease-free. CONCLUSIONS: This study identified a select cohort of patients that did not receive chemotherapy during pregnancy. There were no adverse outcomes to mothers due to delayed treatment.

Detection of estrogen receptor in paraffin-embedded sections of breast carcinoma by immunohistochemistry and in situ hybridization.

Biopsy specimens of small breast carcinomas are often insufficient for both diagnosis and the biochemical determination of estrogen receptor (ER) protein. Recent reports from various laboratories have shown the utility of immunohistochemical detection of ER protein in paraffin-embedded tissue sections. We used immunohistochemical (IHC) staining with the Abbott ER antibody (H222) and in situ hybridization (ISH) analysis with a 35S-labeled and a biotinylated oligonucleotide probe to detect ER protein and messenger RNA (mRNA) in tissue sections of 53 breast carcinomas. The dextran-coated charcoal (DCC) assay of these same cases revealed positive receptor levels in 31 of 53 cases, whereas the IHC method was positive in 33 of 53 cases. ISH for detection of ER mRNA was more sensitive than IHC or the biochemical assay for estrogen binding proteins, as the isotopic probe detected ER mRNA in 47 of 53 cases, whereas the biotinylated probe detected ER mRNA in 46 of 53 cases. These results indicate that ER protein can be readily detected in enzyme-treated paraffin tissue sections and that the IHC detection of ER protein correlates highly with the DCC assay. ISH with isotopic and biotinylated probes detects ER mRNA in most cases found to be positive for ER protein and also in many cases without detectable ER protein. Although detection of ER protein in paraffin sections correlates highly with the biochemical assay in this report and in other reported studies, the clinical significance of increased sensitivity by ISH is unknown and must await clinical correlative follow-up studies.

Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS).

A new case of AIDS-associated, small noncleaved cell (Burkitt's) lymphoma that presented as an orbital mass is described. Extraocular muscle involvement was documented by computed tomography and confirmed by orbital biopsy. Extensive abdominal involvement was subsequently diagnosed and this caused the patient's death only 15 days after the initial consultation and orbital biopsy. A literature review discloses only eight previous case reports of AIDS-associated non-Hodgkin's lymphoma (NHL) involving the orbit: two cases of Burkitt's type and six cases of large cell immunoblastic type. Three additional cases of orbital NHL can be found among larger series of AIDS cases. Affected patients are uniformly young adult males with a history of homosexuality and/or IV drug abuse. Variations in clinical presentation are discussed. Although the morphology of the histopathologic specimen in our case was consistent with a high-grade, small noncleaved cell NHL, flow cytometry revealed an atypical immunophenotype for Burkitt's lymphoma in that CD20 and immunoglobulin light chain antigens were not expressed. Morphologic classification and immunophenotypic characteristics of AIDS-associated NHLs are discussed.

Comparison of type I and type II Chlamydia psittaci strains infecting koalas (Phascolarctos cinereus).

The native Australian marsupial Phascolarctos cinereus, otherwise known as the koala, is prone to infection by the obligate intracellular parasite Chlamydia psittaci, which causes ocular 'pink eye' and urogenital 'dirty tail' diseases. Several chlamydial DNA probes to both chromosomal and plasmid sequences were used to type by Southern blot analysis 51 samples taken from wild and captive koalas from habitats on the eastern seaboard of Australia as far apart as Queensland and Victoria. Two types of C. psittaci were observed and called types I and II. Type II was found more frequently than type I and occurred in both ocular and urogenital samples, while type I showed a strong but not absolute preference for ocular sites. Cross-hybridization analyses indicated that type I and type II had about 10% DNA sequence identity to each other. DNA analyses showed that type II was very closely related to some ovine and bovine chlamydiae but type I could not be related to any other C. psittaci strain available. Light and electron microscopic analyses of infected BGM monolayers revealed that the two strains were similar in morphological characteristics. The type I strain was considerably more infectious than the type II strain in BGM cells and in the yolk sacs of embryonated eggs. A PCR based assay detected both type I and type II koala chlamydiae in samples that had been negative by Southern blot and tissue culture and provided the first evidence that both types can occur simultaneously at the one site of infection.

Episodic gross hematuria in association with allergy symptoms in a child.

BACKGROUND: A relationship between allergy and the development of various renal diseases has been postulated, but never proven. MATERIALS AND METHODS: We present the case of a child with idiopathic episodic gross hematuria. The child also has significant environmental allergies, and his episodes of hematuria coincide with flares of his allergic symptoms. The available literature on hematuria and allergy was reviewed in order to further explore the potential role that allergy may play in the pathogenesis of genitourinary tract disease. CONCLUSIONS: This case, as well as others reported in the literature, suggest that allergy should be considered as a possible diagnosis in children with otherwise unexplained hematuria.

Emergency physician attitudes concerning intervention for alcohol abuse/dependence delivered in the emergency department: a brief report.

Emergency Medicine (EM) physicians frequently see patients with alcohol abuse or dependence (AA/AD). Brief interventions delivered in the Emergency Department (ED) have been advocated for these patients, however, little is known regarding EM physician willingness to support such interventions. We conducted a study to determine EM physicians' attitudes toward the use of interventions for AA/AD in the ED. All members of the Michigan College of Emergency Physicians (n = 569) were mailed a survey to assess their attitudes toward the use of intervention for AA/AD in the ED. Of the 257 respondents (45.9%), a total of 76% agreed that AA/AD is a treatable illness and only 15% would not agree to support of ED interventions. Both supporters and non-supporters thought that the lack of sufficient time was an impediment to treating AA/AD in the ED. Our study suggests that the majority of ED physicians would support the implementation of brief intervention for AA/AD in the ED.