GI.1 Norovirus Neutralizing Antibody Levels Are Correlated with GI.1 Histo-blood Group Antigen-Blocking Antibody Levels.

BACKGROUND: The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histoblood group antigen (HBGA)-blocking assays. METHODS: Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/GI.1 (P1) virus strain. Results were compared to those previously determined using HBGA-blocking assays. RESULTS: Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r=0.81, P<0.001) with those measured by HBGA-blocking. CONCLUSIONS: GI.1-specific HBGA-blocking antibodies are a surrogate for neutralization of GI.1 norovirus.

Long-wave infrared pulsed external-cavity QCL spectrometer using a hollow waveguide gas cell.

A spectrometer built using an external cavity pulsed quantum cascade laser is described. The spectrometer has a tuning range from 10 - 13 µm (1,000 - 769 cm-1) and is designed to target volatile organic compounds (VOCs) which often exhibit water-free molecular absorption within the region. The spectrometer utilizes a hollow silica waveguide gas cell which has an internal volume of a few millilitres, a fast response time (∼1 s), and is advantageous when only low sample volumes, similar to the cell volume, are available. Propane is used as a test gas because it is easy to handle, and its spectral profile is comparable to VOCs of interest. Its absorption in the region is primarily within the ν21 band which spans from 10.55 - 11.16 µm (948 - 896 cm-1). Spectral measurements at a range of concentrations show good linearity and an Allan deviation of absorbance values recorded over a 100-minute period indicates a minimum detectable absorbance of 3.5×10-5 at an integration time of 75 s.

Current status of optoacoustic breast imaging and future trends in clinical application: is it ready for prime time?

Optoacoustic imaging (OAI) is an emerging field with increasing applications in patients and exploratory clinical trials for breast cancer. Optoacoustic imaging (or photoacoustic imaging) employs non-ionizing, laser light to create thermoelastic expansion in tissues and detect the resulting ultrasonic emission. By combining high optical contrast capabilities with the high spatial resolution and anatomic detail of grayscale ultrasound, OAI offers unique opportunities for visualizing biological function of tissues in vivo. Over the past decade, human breast applications of OAI, including benign/malignant mass differentiation, distinguishing cancer molecular subtype, and predicting metastatic potential, have significantly increased. We discuss the current state of optoacoustic breast imaging, as well as future opportunities and clinical application trends. CLINICAL RELEVANCE STATEMENT: Optoacoustic imaging is a novel breast imaging technique that enables the assessment of breast cancer lesions and tumor biology without the risk of ionizing radiation exposure, intravenous contrast, or radionuclide injection. KEY POINTS: • Optoacoustic imaging (OAI) is a safe, non-invasive imaging technique with thriving research and high potential clinical impact. • OAI has been considered a complementary tool to current standard breast imaging techniques. • OAI combines parametric maps of molecules that absorb light and scatter acoustic waves (like hemoglobin, melanin, lipids, and water) with anatomical images, facilitating scalable and real-time molecular evaluation of tissues.

Role of Locoregional Therapies in the Treatment of Thyroid Pathology: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The role of locoregional therapy in the management of thyroid pathology is rapidly evolving. The Society of Interventional Radiology (SIR) Foundation commissioned an international research consensus panel consisting of physicians from multiple disciplines with expertise in the management of benign and malignant thyroid disease. The panel focused on identifying gaps in the current body of literature to establish research priorities that have the potential to shape the landscape of minimally invasive thyroid interventions. The topics discussed were centered on the emerging role of ablation for malignant thyroid tumors and the treatment of large functioning nodules with embolization and ablation. Specifically, the panel prioritized identifying nodule characteristics, including size and location, that are associated with ideal outcomes following thermal ablation for papillary thyroid microcarcinoma through the development of an international registry or a prospective, multi-institutional trial. The panel also prioritized evaluating the role of locoregional therapy in Stage T1b papillary thyroid cancer through a sequence of 2 studies: (a) a Phase I study of ablation followed by immediate resection of Stage T1b papillary thyroid cancer, which may lead to (b) a Phase II prospective, multi-institutional study of ablation followed by biopsy for Stage T1b papillary thyroid cancer. Lastly, the panel prioritized investigating the treatment of large, functioning thyroid nodules >20 mL in volume through a randomized clinical trial or prospective registry comparing embolization alone with embolization followed by ablation.

Micrometeorite collections: a review and their current status.

Micrometeorites are estimated to represent the main part of the present flux of extraterrestrial matter found on the Earth's surface and provide valuable samples to probe the interplanetary medium. Here, we describe large and representative collections of micrometeorites currently available to the scientific community. These include Antarctic collections from surface ice and snow, as well as glacial sediments from the eroded top of nunataks-summits outcropping from the icesheet-and moraines. Collections extracted from deep-sea sediments (DSS) produced a large number of micrometeorites, in particular, iron-rich cosmic spherules that are rarer in other collections. Collections from the old and stable surface of the Atacama Desert show that finding large numbers of micrometeorites is not restricted to polar regions or DSS. The advent of rooftop collections marks an important step into involving citizen science in the study of micrometeorites, as well as providing potential sampling locations over all latitudes to explore the modern flux. We explore their strengths of the collections to address specific scientific questions and their potential weaknesses. The future of micrometeorite research will involve the finding of large fossil micrometeorite collections and benefit from recent advances in sampling cosmic dust directly from the air. This article is part of the theme issue 'Dust in the Solar System and beyond'.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

13 C NMR quantification of polyamine syntheses in rat prostate.

Currently, many prostate cancer patients, detected through the prostate specific antigen test, harbor organ-confined indolent disease that cannot be differentiated from aggressive cancer according to clinically and pathologically known measures. Spermine has been considered as an endogenous inhibitor for prostate-confined cancer growth and its expression has shown correlation with prostate cancer growth rates. If established clinically, measurements of spermine bio-synthesis rates in prostates may predict prostate cancer growth and patient outcomes. Using rat models, we tested the feasibility of quantifying spermine bio-synthesis rates with 13 C NMR. Male Copenhagen rats (10 weeks, n = 6) were injected with uniformly 13 C-labeled L-ornithine HCl, and were sacrificed in pairs at 10, 30, and 60 min after injection. Another two rats were injected with saline and sacrificed at 30 min as controls. Prostates were harvested and extracted with perchloric acid and the neutralized solutions were examined by 13 C NMR at 600 MHz. 13 C NMR revealed measurable ornithine, as well as putrescine-spermidine-spermine syntheses in rat prostates, allowing polyamine bio-synthetic and ornithine bio-catabolic rates to be calculated. Our study demonstrated the feasibility of 13 C NMR for measuring bio-synthesis rates of ornithine to spermine enzymatic reactions in rat prostates. The current study established a foundation upon which future investigations of protocols that differentiate prostate cancer growth rates according to the measure of ornithine to spermine bio-synthetic rates may be developed.

3D Transoral Endoscopic Thyroid.

Transoral endoscopic thyroidectomy with vestibular approach (TOETVA) is a feasible new surgical procedure that does not require visible incisions. We describe our experience with three-dimensional (3D) TOETVA. We recruited 98 patients who were willing to undergo 3D TOETVA. Inclusion criteria were: (a) patients with a neck ultrasound (US) with an estimated thyroid diameter of 10cm or less; (b) estimated US gland volume ≤45ml; (c) nodule size ≤50mm; (d) benign tumor, such as thyroid cyst, goiter with one nodule, or goiter with multiple nodules; (e) follicular neoplasia; and (f) papillary microcarcinoma without evidence of metastases. The procedure is performed using a three-port technique at the oral vestibule, a 10mm port for the 30° endoscope, and two additional 5mm ports for dissecting and coagulation instruments. The CO2 insufflation pressure is set at 6mmHg. An anterior cervical subplatysmal space is created from the oral vestibule to the sternal notch and laterally to the sternocleidomastoid muscle. Thyroidectomy is performed entirely 3D endoscopically with conventional endoscopic instruments and intraoperative neuromonitoring. There were 34% total thyroidectomies and 66% hemithyroidectomies. Ninety-eight 3D TOETVA procedures were successfully performed without any conversions. The mean operative time was 87.6 minutes (59-118 minutes) for lobectomy and 107.6 minutes (99-135 minutes) for bilateral surgery. We observed one case of transient postoperative hypocalcemia. Paralysis of the recurrent laryngeal nerve did not occur. The cosmetic outcome was excellent in all patients. This is the first case series of 3D TOETVA.

Community health workers can be trained to identify patients eligible for tuberculosis preventive therapy, but encounter barriers to programme implementation in KwaZulu-Natal, South Africa.

Tuberculosis (TB) remains one of the top 10 causes of death worldwide, ranking as the leading cause of death from infectious disease, above HIV and AIDS. South Africa has the sixth highest TB incidence rate in the world and the world's largest HIV epidemic. This study sought to demonstrate the feasibility of community health workers (CHWs) contributing to the implementation of tuberculosis preventive therapy (TPT) among people living with HIV and AIDS. Twelve community health workers were trained to test for communicable and non-communicable diseases and screen for TPT eligibility. They visited a select number of homes monthly to conduct screening for HIV, TB and non-communicable diseases. We recorded screening results, rates of referral for TPT, linkage to care - defined as being seen in the clinic for TPT - and treatment initiation. Among the 1 279 community members screened, 248 were identified as living with HIV, 99 (39.9%) individuals were identified as eligible for TPT, and 46 (46.5%) were referred to care. Among those referred, the median age was 39 (IQR 30-48) and 29 (63%) linked to care; 11 (37.9%) of those linked subsequently initiated treatment. In rural South Africa, it is feasible to train CHWs to identify and refer patients eligible for TPT, but losses occurred at each step of the cascade. CHWs can facilitate TPT implementation, although further implementation research exploring and addressing barriers to TPT (on an individual, provider and systems level) should be prioritised to optimise their role in rural resource-limited settings.

Efficacy and Safety of Radiofrequency Ablation of Thyroid Nodules: A Multi-institutional Prospective Cohort Study.

BACKGROUND: Radiofrequency ablation (RFA) has been recently adopted into the practice of thyroidology in the United States, although its use as an alternative to traditional thyroid surgery in Asia and Europe came near the turn of the 21st century. In the United States, only a few studies with small sample sizes have been published to date. We examined outcomes of benign thyroid nodules treated with RFA from 2 North American institutions. METHODS: We performed a prospective, multi-institutional cohort study of thyroid nodules treated with RFA between July 2019 and January 2022. Demographics, sonographic characteristics of thyroid nodules, thyroid function profiles, procedural details, complications, and nodule volume measurements at 1, 3, 6, and 12 months follow-up were evaluated. Adjusted multivariate logistic regression analysis was performed to identify sonographic features associated with treatment failure. RESULTS: A total of 233 nodules were included. The median and interquartile range of volume reduction rate (VRR) at 1, 3, 6, and 12 months were 54% [interquartile range (IQR): 36%-73%], 58% (IQR: 37%-80%), 73% (IQR: 51%-90%), and 76% (IQR: 52%-90%), respectively ( P <0.001). Four patients presented with toxic adenomas. All patients were confirmed euthyroid at 3-month postprocedure follow-up. Two patients developed temporary hoarseness of voice, but no hematoma or nodular rupture occurred postprocedure. Elastography was significantly associated with VRR. Compared with soft nodules, stiff nodules were more likely to have a lower VRR (odds ratio: 11.64, 95% confidence interval: 3.81-35.53, P <0.05), and mixed elasticity was also more likely to have a lower VRR (odds ratio: 4.9; 95% confidence interval: 1.62-14.85, P <0.05). CONCLUSIONS: This is the largest multi-institutional North American study examining thyroid nodule treatment response to RFA. RFA is a safe and effective treatment option that allows preservation of thyroid function with minimal risk of procedural complications.

The future of MRI in radiation therapy: Challenges and opportunities for the MR community.

Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs-at-risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a diverse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.

Revisiting the role of surgery in the treatment of Graves' disease.

Graves' disease (GD) can be managed by antithyroid drugs (ATD), radioactive iodine (RAI) and surgery. Thyroidectomy offers the highest success rates for both primary and persistent disease, yet it is the least recommended or utilized option reaching <1% for primary disease and <25% for persistent disease. Several surveys have found surgery to be the least recommended by endocrinologists worldwide. With the development of remote access thyroidectomies and intraoperative nerve monitoring of the recurrent laryngeal nerve, combined with current knowledge of possible risks associated with RAI or failure of ATDs, revaluation of the benefit to harm ratio of surgery in the treatment of GD is warranted. The aim of this review is to discuss possible reasons for the low proportion of surgery in the treatment of GD, emphasizing an evidence-based approach to the clinicians' preferences for surgical referrals, surgical indications and confronting traditional reasons and concerns relating to the low referral rate with up-to-date data.

Two cases of pineal anlage tumor with molecular analysis.

Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.

One hundred and one consecutive transoral endoscopic parathyroidectomies via the vestibular approach for PHPTH: a worldwide multi-institutional experience.

IMPORTANCE: The transoral vestibular approach for thyroid and parathyroid surgery is being adopted rapidly world-wide. Currently there is a paucity of information on this approach for primary hyperparathyroidism (PHPTH). If this approach is safe and efficacious it would provide patients a completely scarless option for parathyroidectomy. OBJECTIVE: To determine whether parathyroidectomy via the transoral vestibular approach can be successfully done in a safe and efficient manner. DESIGN: Consecutive case series of 101 transoral parathyroidectomies performed over a two-year period. SETTING: Multi-institutional, academic, high-volume transoral thyroidectomy centers from the USA, Israel, and Thailand. PARTICIPANTS: A consecutive series of adult patients with a biochemical diagnosis of classic PHPTH and who met criteria for parathyroidectomy based on established international consensus for surgery for PHPTH. All patients also had well-localized single adenomas on at least two preoperative imaging studies. INTERVENTION: Transoral endoscopic parathyroidectomy vestibular approach. MAIN OUTCOMES AND MEASURES: Surgical success rate defined by immediate intra or post-operative return to normal PTH values. Surgical complications including recurrent laryngeal nerve injury, permanent hypoparathyroidism, and infection. RESULTS: Of the 101 consecutive transoral parathyroidectomy patients 84% were female with an average age of 54.23 ± 11.0 years and an average BMI of 27.35 ± 6.19. Ninety-nine out of the 101 patients had immediate return to normal PTH after resection for a surgical success rate of 98%. There were no permanent recurrent laryngeal nerve injuries, one temporary nerve palsy, and no permanent hypoparathyroidism. The median operative time dropped from 130.5 min (IQR 86) to 66.5 min (IQR 56) between the first- and second-half of cases. CONCLUSION AND RELEVANCE: Transoral endoscopic parathyroidectomy via the vestibular approach is a scarless method of removing parathyroids that is clinically feasible, safe, and efficacious and is a reasonable option for focused minimally invasive parathyroidectomy that can be offered to select patients with PHPTH.

Trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) for the pediatric population: a multicenter, large case series.

INTRODUCTION: A cervical scar has been shown to have an impact on the quality of life of children undergoing thyroid surgery. Transoral endoscopic vestibular thyroidectomy via the vestibular approach (TOETVA) offers the absence of a cutaneous incision, and has not been described to date in the pediatric population. OBJECTIVE: To describe the first series of TOETVA in a pediatric population. PATIENTS AND METHODS: A retrospective, multicenter study, including all patients > 18 years old who underwent TOETVA. Data was prospectively collected and included demographics, preoperative ultrasound, cytology and indications for surgery. Intraoperative parameters included length of surgery and complications, with final pathology and postoperative course also reviewed. TOETVA surgical success was defined as completion of surgery via this approach. RESULTS: Forty-eight children were included. Of these, 43 (89.5%) were girls. The median age was 16 years (range 10-17). The most common indication for surgery was a benign thyroid nodule (n = 26, 54.1%). Eleven patients (22.9%) had papillary thyroid carcinoma on final pathology, of which 90.9% (10/11) were diagnosed pre-operatively based on FNA cytology. Hemithyroidectomy was performed in 36 patients (75%). All surgeries were completed endoscopically. The mean malignant tumor size was 1.4 ± 0.4 cm and all tumors were completely excised with clean margins. No permanent complications were documented. A single patient (2.1%) had transient RLN injury (1.6%, 1/60 nerves at risk). Transient hypocalcemia was documented in 4 of the 12 patients undergoing total thyroidectomy (33.3%). Transient mental nerve injury/chin hypoesthesia was documented in 2 patients (4.2%). CONCLUSIONS: TOETVA appears to be a feasible and safe approach for thyroidectomy in the pediatric population in carefully selected cases, and may be discussed with patients and parents as an alternative for the trans-cervical approach.

Chemiluminescent 1,2-Dioxetane Iridium Complexes for Near-Infrared Oxygen Sensing.

Chemiluminescent iridium-based sensors which demonstrate oxygen dependent responses have been developed. The molecular probes, named IrCL-1, IrCL-2 and IrCL-3 consist of oxygen-sensitive iridium complexes attached to a spiroadamantane 1,2 dioxetane and operate via energy transfer from the chemiexcited benzoate to the corresponding iridium(III) complex. Complexing the iridium(III) center with π-extended ligands results in emission in the biologically relevant, near-infrared (NIR) region. All probes demonstrate varying oxygen tolerance, with IrCL-1 being the most oxygen sensitive. These probes have been further utilized for in vitro ratiometric imaging of oxygen, as well as for intraperitoneal, intramuscular and intratumoral imaging in live mice. To our knowledge, these are the first iridium-based chemiluminescent probes that have been employed for in vitro ratiometric oxygen sensing, and for in vivo tumor imaging.

Regional brain mGlu5 receptor occupancy following single oral doses of mavoglurant as measured by [11C]-ABP688 PET imaging in healthy volunteers.

Mavoglurant binds to same allosteric site on metabotropic glutamate receptor 5 (mGluR5) as [11C]-ABP688, a radioligand. This open-label, single-center pilot study estimates extent of occupancy of mGluR5 receptors following single oral doses of mavoglurant, using [11C]-ABP688 positron emission tomography (PET) imaging, in six healthy males aged 20-40 years. This study comprised three periods and six subjects were divided into two cohorts. On Day 1 (Period 1), baseline clinical data and safety samples were obtained along with PET scan. During Period 2 (1-7 days after Period 1), cohort 1 and 2 received mavoglurant 25 mg and 100 mg, respectively. During Period 3 (7 days after Period 2), cohort 1 and 2 received mavoglurant 200 mg and 400 mg, respectively. Mavoglurant showed the highest distribution volumes in the cingulate region with lower uptake in cerebellum and white matter, possibly because myelinated axonal sheets maybe devoid of mGlu5 receptors. Maximum concentrations of mavoglurant were observed around 2-3.25 h post-dose. Mavoglurant passed the blood-brain barrier and induced dose- and exposure-dependent displacement of [11C]-ABP688 from the mGluR5 receptors, 3-4 h post-administration (27%, 59%, 74%, 85% receptor occupancy for mavoglurant 25 mg, 100 mg, 200 mg, 400 mg dose, respectively). There were no severe adverse effects or clinically significant changes in safety parameters. This is the first human receptor occupancy study completed with Mavoglurant. It served to guide the dosing of mavoglurant in the past and currently ongoing clinical studies. Furthermore, it confirms the utility of [11C]-ABP688 as a unique tool to study drug-induced occupancy of mGlu5 receptors in the living human brain.

Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation.

We examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMNs) in the era of reduced-intensity and nonmyeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4905 1-year survivors of allogeneic HCT for hematologic malignancies (N = 4500) or nonmalignant disorders (N = 405) who received transplants between 1969 and 2014, we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMNs by 30 years after HCT was 22.0%. Compared with age-, sex-, and calendar year-matched Surveillance, Epidemiology, and End Results (SEER) population rates, the standardized incidence ratio (SIR) of SMNs was increased 2.8-fold. The highest SIRs were for SMNs of bones (SIR, 28.8), oral cavity (SIR, 13.8), skin (SIR, 7.3), central nervous system (SIR, 6.0), and endocrine organs (SIR, 4.9). The highest excess absolute risks (EARs) were seen with breast cancer (EAR, 2.2) and cancers of the oral cavity (EAR, 1.5) and skin (EAR, 1.5) per 1000 person-years. The highest incidence of SMNs was in survivors exposed to unfractionated (600-1000 cGy) or high-dose fractionated (1440-1750 cGy) TBI. For patients receiving low-dose TBI, the incidence was comparable to myeloablative chemotherapy alone, although still twofold higher than in the general population. These data demonstrate a strong effect of TBI dose, dose fractionation, and risk of SMNs after HCT. The cumulative incidence of SMNs increases with follow-up time; thus, HCT survivors require lifetime monitoring for early detection and effective therapy of SMNs.

High sensitivity pressure measurement using optical fibre sensors mounted on a composite diaphragm.

A pressure sensor specified for aerodynamic applications and based on optical fibre strain sensors mounted on a circular glass fibre reinforced polymer membrane is presented. The use of two fibre optic strain sensing technologies is explored, the novel intrinsic fibre segment interferometry (FSI) approach and fibre Bragg gratings (FBGs), with the use of FSI shown to offer a pressure resolution that is 15 times larger than that achieved using an FBG. A number of design and fabrication issues are considered, including the position of the fibres relative to the neutral axis of the membrane and the influence of the membrane support structure on the thermal and pressure sensitivities of the sensor, with particular regards to pressure and temperature discrimination.