Engaging oncology and occupational medicine to inform design of a Total Worker Health® intervention to address employment, financial, and well-being outcomes in cancer survivors.

OBJECTIVES: Few Total Worker Health® studies, and fewer interventions, examine well-being in the work context of cancer survivorship. We investigated the possibility of occupation and oncology professionals working together to address employed survivors' work-associated needs. METHODS: We employed a community-based participatory research (CBPR) approach to examine the educational, contextual, and workflow needs of oncology care team members to inform intervention design. Focus groups were conducted with oncology care team members and occupational medicine physicians. Key themes from each group were then examined. RESULTS: Themes included oncology care team's role in helping patients navigate resources, providing psychosocial support, and educating patients. Major themes for ways to better provide employment-related support during treatment included referring patients to employment experts and providing education on employment support. CONCLUSIONS: Occupational health professionals in collaboration with oncology clinics could play an important role in assisting cancer survivors' ability to navigate employment challenges.

Magnetization dynamics in skyrmions due to high-speed carrier injections from Dirac half-metals.

Recent developments in the magnetization dynamics in spin textures, particularly skyrmions, offer promising new directions for magnetic storage technologies and spintronics. Skyrmions, characterized by their topological protection and efficient mobility at low current density, are increasingly recognized for their potential applications in next-generation logic and memory devices. This study investigates the dynamics of skyrmion magnetization, focusing on the manipulation of their topological states as a basis for bitwise data storage through a modified Landau-Lifshitz-Gilbert equation (LLG). We introduce spin-polarized electrons from a topological ferromagnet that induce an electric dipole moment that interacts with the electric gauge field within the skyrmion domain. This interaction creates an effective magnetic field that results in a torque that can dynamically change the topological state of the skyrmion. In particular, we show that these torques can selectively destroy and create skyrmions, effectively writing and erasing bits, highlighting the potential of using controlled electron injection for robust and scalable skyrmion-based data storage solutions.

Guidelines for communicating commensurate magnetic structures. A report of the International Union of Crystallography Commission on Magnetic Structures.

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures.

Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli.

The mesolimbic dopamine (DA) system (MDS) is the canonical "reward" pathway that has been studied extensively in the context of the rewarding properties of sex, food, and drugs of abuse. In contrast, very little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli. Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc) core codes for the salience of social stimuli through the phasic release of DA in response to both rewarding and aversive social stimuli. In contrast, we hypothesize that projections from the lateral VTA to the NAc shell codes for the rewarding properties of social stimuli by increasing the tonic release of DA and the aversive properties of social stimuli by reducing the tonic release of DA. Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA signaling in the NAc core or shell while rewarding and aversive social interactions were taking place. These findings, as well as additional anatomical and functional studies, provide strong support for the proposed neural circuitry underlying the response of the MDS to social stimuli. Together, these data provide a novel conceptualization of how the functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion. Significance Statement: Social interactions of both positive and negative valence are highly salient stimuli that profoundly impact social behavior and social relationships. Although DA projections from the VTA to the NAc are involved in reward and aversion little is known about their role in the saliency and valence of social stimuli. Here, we report that DA projections from the mVTA to the NAc core signal the salience of social stimuli, whereas projections from the lVTA to the NAc shell signal valence of social stimuli. This work extends our current understanding of the role of DA in the MDS by characterizing its subcircuit connectivity and associated function in the processing of rewarding and aversive social stimuli.

Ocular findings in Jansen metaphyseal chondrodysplasia.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging.

The Risk of Postpartum Hemorrhage with Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors: Preliminary Results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

Background: Previous studies suggest an association between late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and increased postpartum hemorrhage (PPH) risk. This is the first pregnancy registry study to compare PPH outcomes among women with psychiatric illness exposed or unexposed to SSRIs/SNRIs proximate to delivery. Methods: This study used data from the National Pregnancy Registry for Psychiatric Medications to evaluate the relationship between SSRI/SNRI exposure in late pregnancy and PPH risk. The sample included n = 953 participants with retrospectively collected medical record data on postpartum blood loss, n = 453 unexposed to SSRIs/SNRIs during pregnancy, and n = 500 exposed at least during the week of delivery. PPH was defined as an estimated blood loss ≥500 mL following vaginal delivery or ≥1,000 mL following cesarean section (C-section), with onset of excessive bleeding occurring within the first 24 hours postpartum. Univariate and multivariate logistic regression analyses were performed to determine odds ratios. Results: Overall PPH incidence was 13.1%. SSRI/SNRI exposure was associated with a PPH unadjusted odds ratio of 1.42 compared to no exposure (95% confidence interval [CI: 0.97, 2.08]) and an adjusted odds ratio of 1.33 (95% CI [0.90, 1.97]). When stratified by delivery type, the odds ratio following vaginal delivery among women exposed to SSRIs/SNRIs was 1.04 (95% CI [0.63, 1.70]) versus 2.31 (95% CI [1.25, 4.26]) for C-section delivery; the adjusted C-section odds ratio was 2.21 (95% CI [1.18, 4.13]). Conclusions: Although these findings align with accumulating evidence suggesting SSRI/SNRI exposure may confer a modestly increased risk of PPH, particularly after C-section, the study was underpowered to make definitive conclusions. These preliminary data highlight the need for further research with larger sample sizes. Nevertheless, the findings underscore the importance of greater clinical monitoring for PPH following C-section, especially in women who may have other known PPH risk factors and are exposed to SSRIs/SNRIs in late pregnancy.

Characterization of concrete reference material for analysis of artificial radionuclides in nuclear power plant decommissioning waste.

The decommissioning of nuclear power plants has led to a surge in the production of radioactive waste, necessitating the development of accurate and reliable measurement methods for safe waste disposal. This study presents the development of a new concrete reference material (RM) containing beta, and gamma nuclides for quality assurance and quality control (QA/QC) in concrete measurements. The newly developed RM manufacturing method was used to ensure sample homogeneity; rigorous processes were followed according to ISO guidelines. The RM, designed to mimic real waste matrices, targeted six radionuclides: 60Co, 134Cs, 137Cs, 152Eu, 154Eu, and 90Sr. Homogeneity and stability tests, conducted according to ISO guidelines, confirmed the suitability of the concrete RM for QA/QC purposes. Reference values for the six radionuclides in RM ranged from 66.0 to 172.6 Bq kg-1. The expanded uncertainties of the reference values, at a 95 % confidence level (k = 2), ranged from approximately 7.1 %-17.2 %. The developed RM holds potential as proficiency test material and for validating and verifying analytical methods in radioactive waste analysis. Additionally, the manufacturing method introduced here opens doors for diverse applications, enabling the production of accurate and reliable reference materials for various waste matrices.

Application and comparison of point-of-care devices for field evaluation of underlying health status of Guatemalan sugarcane workers.

With chronic disease prevalence on the rise globally, surveillance and monitoring are critical to improving health outcomes. Point-of-care (POC) testing can facilitate epidemiological research and enhance surveillance systems in limited resource settings, but previous research has identified bias between POC devices and laboratory testing. We compared the performance of two POC blood analyzers, the iSTAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) to concurrent blood samples analyzed at a local laboratory that were collected from 89 agricultural workers in Guatemala. We measured creatinine and other measures of underlying health status with the POC and the lab blood samples. Pearson correlation coefficients, Bland-Altman plots, no intercept linear regression models and two-sample t-tests were used to evaluate the agreement between the POC and lab values collected across three study days and to assess differences by study day in a field setting. On average there was no observed difference between the iSTAT and lab creatinine measurements (p = 0.91), regardless of study day. Using lab creatinine as the gold standard, iSTAT creatinine results were more accurate compared to the Statsensor, which showed some bias, especially at higher values. The iSTAT had good agreement with the lab for sodium and blood urea nitrogen (BUN), but showed differences for potassium, anion gap, bicarbonate (TCO2), glucose, and hematocrit. In this tropical field setting, the research team devised a protocol to prevent the devices from overheating. In limited resource settings, POC devices carry advantages compared to traditional lab analyses, providing timely results to patients, researchers, and healthcare systems to better evaluate chronic health conditions. Technical challenges due to use of POC devices in high heat and humidity environments can be addressed using a standard protocol for transporting and operating the devices.

Increased risk of haematological malignancy in adults over age 60 with thrombocytopenia compared with matched controls: Time for an upfront bone marrow evaluation?

International societies have conflicting recommendations on whether bone marrow aspirate/biopsy (BMB) is needed during workup for isolated thrombocytopenia. Our objective was to determine if thrombocytopenia in patients aged ≥60 years is associated with an increased incidence of haematological malignancy. We performed a retrospective population-based cohort study in patients aged ≥60 years between January 1, 2009 to December 31, 2019. Exposed patients had specialist consultation for thrombocytopenia, with platelet count <100 × 109/L, but normal haemoglobin and white blood cell count. Unexposed patients were those who never had specialist consultation for thrombocytopenia and whose platelets were ≥100 × 109/L. The primary outcome was the diagnosis of haematological malignancy using a competing risk of death model. During 4.0 years (IQR 2.2-6.7) of follow-up, 378/4930 exposed (19.1/1000PY, 95% CI 17.1-21.0), and 204/17556 unexposed patients (2.5/1000PY, 95% CI 2.2-2.8) were diagnosed with haematological malignancy (HR 15.5 (95% CI 11.3-21.4, p < 0.0001) in year 1, and 5.3 (95% CI 4.4-6.6, p < 0.0001) in years 2+). This finding persisted in analyses stratified by sex, age, severity, or duration of thrombocytopenia, and treatment with corticosteroids within 2 weeks of consultation. This study found a strong association between isolated thrombocytopenia and haematological malignancy in patients ≥60 years, supporting consideration of diagnostic testing including BMB during outpatient specialist consultation.

The first experimental results from W divertor utilizing x-ray imaging crystal spectrometer on KSTAR.

The x-ray imaging crystal spectrometer (XICS) for Korea Superconducting Tokamak Advanced Research is applied to measure multiple atomic states, such as Ar16+, Ar17+, W43+, and W44+, with keeping the same spectrometer configuration because all spectra are well separated within the detector boundary. The first experimental results from the recently installed full W tiles in the lower divertor utilizing the XICS are discussed.

Improvements on stability criteria for linear systems with a time-varying delay via novel delay-dependent Lyapunov functionals.

This work investigates the less conservative stability conditions for linear systems with a time-varying delay. At first, augmented Lyapunov-Krasovskii functionals(LKFs) are constructed with state vectors that have not been utilized in the existing works, and an augmented zero equality that can be derived according to the augmented vector is proposed. By utilizing them, a stability condition is proposed in the form of a linear matrix inequality. And, by using novel delay-dependent LKFs and the introduced ones, improved results are obtained than the previous result. The addition of the delay-dependent LKFs increases the number of decision variables in the results. Therefore, any vectors of integral inequalities utilized in the proposed criterion are appropriately adjusted to reduce computational complexity. To check the excellence and validity of the proposed results, several numerical examples are applied.

Early childhood height is a determinant of young adult stature in rural Nepal.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history. RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt. CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

U-PRO-CRM: designing patient-centred dose-finding trials with patient-reported outcomes.

BACKGROUND: Determining the maximum tolerated dose (MTD) remains the primary objective for the majority of dose-finding oncology trials. Whilst MTD determination often relies upon clinicians to identify dose-limiting toxicities (DLTs) experienced by patients during the trial, research suggests that clinicians may underreport patient's adverse events. Therefore, contemporary practice may be exposed to recommending intolerable doses to patients for further investigation in subsequent trials. There is increasing interest in patients self-assessing their own symptoms using patient-reported outcomes (PROs) in dose-finding trials. DESIGN: We present Utility-PRO-Continual Reassessment Method (U-PRO-CRM), a novel trial design which simultaneously uses clinician-rated and patient-rated DLTs (Clinician-DLTs and Patient-DLTs, respectively) to make dose (de-)escalation decisions and to recommend an MTD. U-PRO-CRM contains the published PRO-CRM as a special case and provides greater flexibility to trade-off the rate of Patient-DLTs and Clinician-DLTs to find an optimal dose. We present simulation results for U-PRO-CRM. RESULTS: For specified trade-offs between Clinician-DLT and Patient-DLT rate, U-PRO-CRM outperforms the PRO-CRM design by identifying the true MTD more often. In the special case where U-PRO-CRM generalises to PRO-CRM, U-PRO-CRM performs as well as its published counterpart. U-PRO-CRM minimises the number of patients overdosed whilst maintaining a similar proportion of patients allocated to the true MTD. CONCLUSIONS: By using a utility-based dose selection approach, U-PRO-CRM offers the flexibility to define a trade-off between the risk of patient-rated and clinician-rated DLTs for an optimal dose. Patient-centric dose-finding strategies, which integrate PROs, are poised to assume an ever more pivotal role in significantly advancing our understanding of treatment tolerability. This bears significant implications in shaping the future landscape of early-phase trials.

An innovative model of delivering cancer care in the community: the experience of a tertiary cancer centre in Singapore.

BACKGROUND: Cancer care has evolved rapidly, increasing the demand on healthcare resources. While many non-oral cancer treatments are administered in the hospital, not all necessitate complex medical care. Treatments that can be administered subcutaneously, intramuscularly, or as short intravenous infusions with a low risk of extravasation can be safely administered in the community. PATIENTS AND METHODS: Since 2017, the National University Cancer Institute, Singapore (NCIS) has operated a program called NCIS on-the-go (NOTG) comprising a network of community cancer treatment clinics located within 20 km of the hospital. NOTG provides 17 low-risk treatments and nursing services run by oncology-trained nurses without on-site physicians. Patients who receive their first dose of cancer treatment uneventfully in the cancer centre can opt-in to receive subsequent doses at any NOTG clinic. RESULTS: Treatment at NOTG has become more mainstream over the years, with its workload increasing by over sevenfold since 2017, and is now responsible for ∼10% of the total main cancer centre workload. The program is sustainable and financially viable to operate. A survey of 155 patients revealed a 96.8% user satisfaction rate, with the majority reporting tangible savings in travelling time, waiting time, and travelling costs. The diversion of low-risk treatments to NOTG has indirectly increased capacity and reduced waiting times at the main cancer centre for patients requiring complex cancer treatments, resulting in a win-win situation. CONCLUSIONS: NOTG represents an innovative model of care to deliver low-risk cancer treatments safely in the community and can be easily replicated in other countries.

Manipulation of feeding patterns in high fat diet fed rats improves microbiota composition dynamics, inflammation and gut-brain signaling.

Chronic consumption of high fat (HF) diets has been shown to increase meal size and meal frequency in rodents, resulting in overeating. Reducing meal frequency and establishing periods of fasting, independently of caloric intake, may improve obesity-associated metabolic disorders. Additionally, diet-driven changes in microbiota composition have been shown to play a critical role in the development and maintenance of metabolic disorders. In this study, we used a pair-feeding paradigm to reduce meal frequency and snacking episodes while maintaining overall intake and body weight in HF fed rats. We hypothesized that manipulation of feeding patterns would improve microbiota composition and metabolic outcomes. Male Wistar rats were placed in three groups consuming either a HF, low fat diet (LF, matched for sugar), or pair-fed HF diet for 7 weeks (n = 11-12/group). Pair-fed animals received the same amount of food consumed by the HF fed group once daily before dark onset (HF-PF). Rats underwent oral glucose tolerance and gut peptide cholecystokinin sensitivity tests. Bacterial DNA was extracted from the feces collected during both dark and light cycles and sequenced via Illumina MiSeq sequencing of the 16S V4 region. Our pair-feeding paradigm reduced meal numbers, especially small meals in the inactive phase, without changing total caloric intake. This shift in feeding patterns reduced relative abundances of obesity-associated bacteria and maintained circadian fluctuations in microbial abundances. These changes were associated with improved gastrointestinal (GI) function, reduced inflammation, and improved glucose tolerance and gut to brain signaling. We concluded from these data that targeting snacking may help improve metabolic outcomes, independently of energy content of the diet and hyperphagia.

Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide.

OBJECTIVE: During infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice. METHODS: We challenged 10- to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 µg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland. RESULTS: LPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection. CONCLUSIONS: Our data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.

A new certified reference material IAEA-465 for radionuclides in Baltic Sea sediment.

Certified reference material (CRM) for natural (40K,210Pb,210Po,226Ra,228Ra,228Th,230Th,232Th,234U,235U, and238U) and anthropogenic (137Cs,239+240Pu, and241Am) radionuclides in marine sediment from the Baltic Sea (IAEA-465) has been developed. Information values are given for 238Pu,239Pu and240Pu. Altogether 27 laboratories participated in this exercise. Radiometric (alpha-spectrometry, gamma-spectrometry and beta counting, as well as mass spectrometry (ICP-MS and AMS) techniques were applied in measurements. The CRM is intended to be used for Quality Assurance/Quality Control of radionuclide analyses, for the development and validation of analytical methods, for the development of reference methods and for training purposes.

A Germline ZFX Missense Variant in a Patient With Primary Hyperparathyroidism.

A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease.