Deep Integration of Fiber-Optic Communication and Sensing Systems Using Forward-Transmission Distributed Vibration Sensing and on-off Keying.

The deep integration of communication and sensing technology in fiber-optic systems has been highly sought after in recent years, with the aim of rapid and cost-effective large-scale upgrading of existing communication cables in order to monitor ocean activities. As a proof-of-concept demonstration, a high-degree of compatibility was shown between forward-transmission distributed fiber-optic vibration sensing and an on-off keying (OOK)-based communication system. This type of deep integration allows distributed sensing to utilize the optical fiber communication cable, wavelength channel, optical signal and demodulation receiver. The addition of distributed sensing functionality does not have an impact on the communication performance, as sensing involves no hardware changes and does not occupy any bandwidth; instead, it non-intrusively analyzes inherent vibration-induced noise in the data transmitted. Likewise, the transmission of communication data does not affect the sensing performance. For data transmission, 150 Mb/s was demonstrated with a BER of 2.8 × 10-7 and a QdB of 14.1. For vibration sensing, the forward-transmission method offers distance, time, frequency, intensity and phase-resolved monitoring. The limit of detection (LoD) is 8.3 pε/Hz1/2 at 1 kHz. The single-span sensing distance is 101.3 km (no optical amplification), with a spatial resolution of 0.08 m, and positioning accuracy can be as low as 10.1 m. No data averaging was performed during signal processing. The vibration frequency range tested is 10-1000 Hz.

Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML.

PURPOSE: Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131I-apamistamab with conventional care. METHODS: SIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131I-apamistamab-led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population. RESULTS: The ITT population included 153 patients (131I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131I-apamistamab and conventional care groups, respectively. CONCLUSION: The 131I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131I-apamistamab was well tolerated and could address an unmet need in this population.

Distributed Vibration Sensing Based on a Forward Transmission Polarization-Generated Carrier.

For distributed fiber-optic sensors, slowly varying vibration signals down to 5 mHz are difficult to measure due to low signal-to-noise ratios. We propose and demonstrate a forward transmission-based distributed sensing system, combined with a polarization-generated carrier for detection bandwidth reduction, and cross-correlation for vibration positioning. By applying a higher-frequency carrier signal using a fast polarization controller, the initial phase of the known carrier frequency is monitored and analyzed to demodulate the vibration signal. Only the polarization carrier needs to be analyzed, not the arbitrary-frequency signal, which can lead to hardware issues (reduced detection bandwidth and less noise). The difference in arrival time between the two detection ends obtained through cross-correlation can determine the vibration position. Our experimental results demonstrate a sensitivity of 0.63 mrad/µÎµ and a limit of detection (LoD) of 355.6 pε/Hz1/2 at 60 Hz. A lock-in amplifier can be used on the fixed carrier to achieve a minimal LoD. The sensing distance can reach 131.5 km and the positioning accuracy is 725 m (root-mean-square error) while the spatial resolution is 105 m. The tested vibration frequency range is between 0.005 Hz and 160 Hz. A low frequency of 5 mHz for forward transmission-based distributed sensing is highly attractive for seismic monitoring applications.

High pressure sensor based on intensity-variation using polymer optical fiber.

Silica fiber under high pressure increases the risk of fiber breakage or permanent deformation, which may cause sensor failure due to mechanical strength limitations. High pressure can also induce birefringence in optical fiber. In this study, we present a simple design and low-cost high pressure sensor using polymer optical fiber (POF) based on the intensity-variation technique. A side-coupling mechanism in the sensor structure is adopted, which varies the intensity with applied pressure. Two POFs are twisted together to create a sensing region where the light is launched in the first fiber and measurement is taken from the second fiber. In sensing phenomena, cladding mode frustrated total internal reflection occurs when pressure increases. Silicone gel is used in the pressure chamber for sealing and preventing leakage. The sensor structure is able to detect high pressure in the MPa range, where we tested up to 4 MPa. For higher sensitivity, twisted and bend structure is analyzed, and sensitivity is achieved at about 432.21 nW/MPa. However, twisted helical structure is adopted to enhance sensing range which is about 50 cm. The proposed high-pressure sensor structure is easier to fabricate and has high stability because it doesn't require any destructive method as compared to other conventional methods.

Gastrointestinal involvement refines prognosis in minnesota standard risk acute graft-vs.-host disease.

Minnesota acute graft versus host disease (AGVHD) risk score is a validated tool to stratify newly-diagnosed patients into standard-risk (SR) and high-risk (HR) groups with ~85% having SR AGVHD. We aimed to identify factors for further risk-stratification within Minnesota SR patients. A single-center, retrospective analysis of consecutive patients between 1/2010 and 12/2014 was performed. Patients who developed AGVHD within 100 days and treated with systemic corticosteroids were included (N = 416), 356 (86%) of which were Minnesota SR and 60 (14%) had HR AGVHD. Isolated upper gastrointestinal (GI) AGVHD patients had significantly better day 28 and 56 CR/PR rates (90% vs. 72%, p = 0.004) and (83% vs 66%, p = 0.01), respectively, and lower 1-year non-relapse mortality (NRM; 10% vs. 22%; HR 0.4, p = 0.03). Lower GI AGVHD had less favorable outcomes with 1-year NRM of 40% (HR 2.1, p = 0.001), although CR/PR rates were not statistically different. In multivariate analysis, lower GI involvement (HR 2.6, p < 0.001), age ≥ 50 (HR 2.9, p < 0.001) and HCT-CI > 3 (HR 2.1, p = 0.002) predicted for 1-year NRM. Heterogeneity within Minnesota SR patients requires consideration in clinical trials, as distinct outcomes are observed in those with isolated upper GI and lower GI AGVHD, highlighting the importance of stratification in clinical trial design.

Conversion of high moisture biomass to hierarchical porous carbon via molten base carbonisation and activation for electrochemical double layer capacitor.

Biomass-derived carbon for supercapacitors faces the challenge of achieving hierarchical porous carbon with graphitic structure and specific heteroatoms through a single-stage thermal process that minimises resource input. Herein, molten base carbonisation and activation is proposed. The process utilises the inherent moisture of Moso bamboo shoots, coupled with a low amount of KOH, to form potassium organic salts before drying. The resultant potassium salts promote in-situ activation during single-stage heating process, yielding hierarchical porous, large specific surface area, and partially graphitised carbon with heteroatoms (N, O). As an electrode material, this carbon exhibits a specific capacitance of 327F g-1 in 6 M KOH and 182F g-1 in 1 M TEABF4/AN, demonstrating excellent cycling stability over 10,000 cycles at 2 A/g. Overall, this study presents a straightforward process that avoids pre-drying of biomass, minimises base consumption, and employs single-stage heating to fabricate electrode carbon suitable for supercapacitors.

Study Protocol: Predicting the Quality of Response to Specific Treatments (PQRST) in Chronic Graft-versus-Host Disease.

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Despite significant progress in chronic GVHD therapies, challenges remain in understanding pleomorphic phenotypes and varying response to treatment. The goal of the Predicting the Quality of Response to Specific Treatments (PQRST) in chronic GVHD study is to identify predictors of treatment response. This report describing the study design seeks to raise awareness and invite collaborations with investigators who wish to access clinical data and research samples from this study. METHODS: This is a prospective, observational cohort study involving data collection from patients who are beginning first-, second-, or third-line systemic therapy for chronic GVHD with defined agents. Evaluable participants will have baseline assessments and research samples prior to starting the index therapy, and 1 month after starting treatment. Response assessments occur at 3 and 6 months after start of treatment, or if a new systemic therapy is started before 6 months. Target enrollment is approximately 200 patients at 8 institutions, with at least 6 months of follow up to determine response to index therapy. RESULTS: Enrollment started in July 2020 and was delayed due to the COVID-19 pandemic; as of 3/1/2024, 137 evaluable participants have been enrolled. DISCUSSION: The Chronic GVHD Consortium "PQRST" is a large longitudinal cohort study that aims to investigate predictors of treatment response by identifying biologically and clinically defined patient subgroups. We welcome investigators to collaborate in the use of these data. TRIAL REGISTRATION: NCT04431479.

Role of hematological and neurological expressed 1 (HN1) in human cancers.

Hematological and neurological expressed 1 (HN1), also known as Jupiter microtubule associated homolog 1 (JPT1), is a highly conserved protein with widespread expression in various tissues. Ectopic elevation of HN1 has been observed in multiple cancers, highlighting its role in tumorigenesis and progression. Both proteomics and transcriptomics reveal that HN1 is closely associated with severe disease progression, poor prognostic and shorter overall survival. HN1's involvement in cancer cell proliferation and metastasis has been extensively investigated. Overexpression of HN1 is associated with increased tumor growth and disease progression, while its depletion leads to cell cycle arrest and apoptosis. The pivotal role of HN1 in cancer progression, particularly in proliferation, migration, and invasion, underscores its significance in cancer metastasis. Validation of the efficacy and safety of HN1 inhibition, along with the development of diagnostic methods to determine HN1 expression levels in patients, is essential for the translation of HN1-targeted therapies into clinical practice. Overall, HN1 emerges as a valuable prognostic marker and therapeutic target in cancer, and further investigations hold the potential to improve patient outcomes by impeding metastasis and enhancing treatment strategies.

Neural topic models with survival supervision: Jointly predicting time-to-event outcomes and learning how clinical features relate.

We present a neural network framework for learning a survival model to predict a time-to-event outcome while simultaneously learning a topic model that reveals feature relationships. In particular, we model each subject as a distribution over "topics", where a topic could, for instance, correspond to an age group, a disorder, or a disease. The presence of a topic in a subject means that specific clinical features are more likely to appear for the subject. Topics encode information about related features and are learned in a supervised manner to predict a time-to-event outcome. Our framework supports combining many different topic and survival models; training the resulting joint survival-topic model readily scales to large datasets using standard neural net optimizers with minibatch gradient descent. For example, a special case is to combine LDA with a Cox model, in which case a subject's distribution over topics serves as the input feature vector to the Cox model. We explain how to address practical implementation issues that arise when applying these neural survival-supervised topic models to clinical data, including how to visualize results to assist clinical interpretation. We study the effectiveness of our proposed framework on seven clinical datasets on predicting time until death as well as hospital ICU length of stay, where we find that neural survival-supervised topic models achieve competitive accuracy with existing approaches while yielding interpretable clinical topics that explain feature relationships. Our code is available at: https://github.com/georgehc/survival-topics.

Comparison of treatment response measures in cutaneous sclerosis after allogeneic hematopoietic cell transplantation.

ABSTRACT: Cutaneous sclerosis, a highly morbid subtype of chronic graft-versus-host disease (GVHD), demonstrates limited treatment response under current National Institutes of Health (NIH) response measures. We explored novel sclerosis-specific response measures using Chronic GVHD Consortium data. A training cohort included patients with cutaneous sclerosis from a randomized trial of imatinib vs rituximab and a consortium observational study. The validation cohort was a different consortium observational study. Clinician-reported measures (baseline and baseline to 6-month change) were examined for association with 6-month clinician-reported response. Patient-reported measures (baseline and baseline to 6-month change) were studied for association with 6-month patient-reported response. A total of 347 patients were included (training 183 and validation 164). Although multiple skin and joint measures were associated with clinician-reported response on univariate analysis, patient range of motion (PROM) total score, PROM total score change, and NIH 0 to 3 skin change were retained in the final multivariate model (area under the receiver operating characteristic curve [AUC], 0.83 training and 0.75 validation). Similarly, many patient-reported measures were associated, but final multivariate analysis retained the human activity profile adjusted activity score (AAS), 36 item short form health survey (SF36) vitality change, Lee symptom scale (LSS) skin, and LSS skin change in the model (AUC, 0.86 training and 0.75 validation). We identified which sclerosis measures have the greatest association with 6-month clinician- and patient-reported treatment responses, a previously unstudied area. However, given the observed performance in the validation cohorts, we conclude that further work is needed. Novel response measures may be needed to optimally assess treatment response in cutaneous sclerosis.

Impact of nutrient deficiency on biological sewage treatment - Perspectives towards urine source segregation.

Human urine contains 9 g/L of nitrogen (N) and 0.7 g/L of phosphorus (P). The recovery of N and P from urine helps close the nutrient loop and increase resource circularity in the sewage treatment sector. Urine contributes an average of 80 % N and 50 % P in sewage, whereby urine source segregation could reduce the burden of nutrient removal in sewage treatment plants (STPs) but result in N and P deficiency and unintended negative consequences. This review examines the potential impacts of N and P deficiency on the removal of organic carbon and nutrients, sludge characteristics and greenhouse gas emissions in activated sludge processes. The details of how these impacts affect the operation of STPs were also included. This review helps foresee operational challenges that established STPs may face when dealing with nutrient-deficient sewage in a future where source separation of urine is the norm. The findings indicate that the requirement of nitrification-denitrification and biological P removal processes could shrink at urine segregation above 80 % and 100 %, respectively. Organic carbon, N and biological P removal processes can be severely affected under full urine segregation. The decrease in solid retention time due to urine segregation increases treatment capacity up to 48 %. Sludge flocculation and settleability would deteriorate due to changes in extracellular polymeric substances and induce various forms of bulking. Beneficially, N deficiency reduces nitrous oxide emissions. These findings emphasise the importance of considering and preparing for impacts caused by urine source segregation-induced nutrient deficiency in sewage treatment processes.

Strategies for Accelerated Drug Development: An Industry Perspective Based on an IQ Consortium Survey of CMC Considerations.

Over the past decade, there has been an increase in accelerated drug development with successful regulatory approval that has provided rapid access of novel medicines to patients world-wide. This has created the opportunity for the pharmaceutical industry to continuously improve the process of quickly bringing new medicines to patients with unmet medical needs. This can be accomplished through sharing the learnings and advancements in drug development, enhancing regulatory interactions, and collaborating with academics on developing the underlying science to reduce drug development timelines. In this paper, the IQ Consortium - Accelerated Drug Development working group members intend to share recommendations for optimizing strategies that build efficiencies in accelerated pathways for regulatory approval. Information was obtained by surveying member pharmaceutical companies with respect to recent expedited submissions within the past 5 years to gain insights as to which development strategies were successful. The learnings from this analysis are provided, which includes shared learnings in formulation development, stability, analytical methods, manufacturing, and importation testing as well as regulatory considerations. Each of these sections provide a summary illustrating the key data collected as well as a discussion that is aimed to guide pharmaceutical companies on strategies to consider streamlining development activities and expedite the drug to market.

Study protocol: Close Assessment and Testing for Chronic Graft-vs.-Host disease (CATCH).

Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration: This study is registered at www.clinicaltrials.gov as NCT04188912.

Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas.

BACKGROUND: Despite advances in detection and treatments, biliary tract cancers continue to have poor survival outcomes. Currently, there is limited data investigating the significance of socioeconomic status, race/ethnicity, and environmental factors in biliary tract cancer survival. AIM: To investigate how socioeconomic status and race/ethnicity are associated with survival. METHODS: Data from the Surveillance, Epidemiology, and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016. Socioeconomic data included smoking, poverty level, education, adjusted household income, and percentage of foreign-born persons and urban population. Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis. RESULTS: Our study included 15883 gallbladder, 11466 intrahepatic biliary, 12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases. When analyzing county-specific demographics, patients from counties with higher incomes were associated with higher survival rates [hazard ratio (HR) = 0.97, P <0.05]. Similarly, counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates (HR = 0.96, P = 0.002 and HR = 0.97, P = 0.004, respectively). CONCLUSION: Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

Demonstration of a low loss, highly stable and re-useable edge coupler for high heralding efficiency and low g(2)(0) SOI correlated photon pair sources.

We report a stable, low loss method for coupling light from silicon-on-insulator (SOI) photonic chips into optical fibers. The technique is realized using an on-chip tapered waveguide and a cleaved small core optical fiber. The on-chip taper is monolithic and does not require a patterned cladding, thus simplifying the chip fabrication process. The optical fiber segment is composed of a centimeter-long small core fiber (UHNA7) which is spliced to SMF-28 fiber with less than -0.1 dB loss. We observe an overall coupling loss of -0.64 dB with this design. The chip edge and fiber tip can be butt coupled without damaging the on-chip taper or fiber. Friction between the surfaces maintains alignment leading to an observation of ±0.1 dB coupling fluctuation during a ten-day continuous measurement without use of any adhesive. This technique minimizes the potential for generating Raman noise in the fiber, and has good stability compared to coupling strategies based on longer UHNA fibers or fragile lensed fibers. We also applied the edge coupler on a correlated photon pair source and observed a raw coincidence count rate of 1.21 million cps and raw heralding efficiency of 21.3%. We achieved an auto correlation function g H(2)(0) as low as 0.0004 at the low pump power regime.

Enhancer-targeted CRISPR-Activation Rescues Haploinsufficient Autism Susceptibility Genes.

Autism Spectrum Disorder (ASD) is a highly heritable condition with diverse clinical presentations. Approximately 20% of ASD's genetic susceptibility is imparted by de novo mutations of major effect, most of which cause haploinsufficiency. We mapped enhancers of two high confidence autism genes - CHD8 and SCN2A and used CRISPR-based gene activation (CRISPR-A) in hPSC-derived excitatory neurons and cerebral forebrain organoids to correct the effects of haploinsufficiency, taking advantage of the presence of a wildtype allele of each gene and endogenous gene regulation. We found that CRISPR-A induced a sustained increase in CHD8 and SCN2A expression in treated neurons and organoids, with rescue of gene expression levels and mutation-associated phenotypes, including gene expression and physiology. These data support gene activation via targeting enhancers of haploinsufficient genes, as a therapeutic intervention in ASD and other neurodevelopmental disorders.

Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience.

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.