Intermediate Intensity Research Articles

The effect and mechanism of motor control exercise on low back pain: a narrative review.

Low back pain (LBP) is a common symptom that can occur in all ages. It is the first common cause of disability globally and is associated with over 60 million disability-adjusted life-years in a single year. Motor control exercise (MCE) has obtained increasing attention in treating LBP. However, the findings from distinct meta-analyses differed and some even reached controversial conclusions. More importantly, how MCE improves LBP-related symptoms remains unclear. The primary aim of this study is to describe the possible improvement mechanisms of MCE on LBP from brain, biochemistry, inflammatory, and neuromuscular aspects. The secondary aim is to further conclude its effectiveness and clinical application. Further understanding of mechanisms and effectiveness could be instructive for future LBP treatments and provide more information for clinicians when making prescriptions. MCE is effective in alleviating pain and disability among patients with acute and chronic LBP. Notably, the evidence for acute LBP is relatively low-quality and limited. MCE might be more effective for patients with specific LBP characteristics, especially those with pre-diagnosis of impaired transversus abdominis recruitment, intermediate pain intensity, and longer MCE training duration. MCE could remap brain representation and reverse negative brain alternation, induce exercise-induced hypoalgesia, mediate anti-inflammatory response, retain normal activation, and improve morphological deficits.

T2-star (T2*)-weighted magnetic resonance imaging of tenosynovial giant cell tumors

PurposeTenosynovial giant cell tumors (TSGCTs) are benign but aggressive lesions, and the treatment is resection. A low to intermediate signal intensity on both T1- and T2-weighted images of magnetic resonance imaging (MRI) is characteristic, which is similar to the signal intensity of muscle, and therefore can be challenging for lesion detection. T2-star (T2*)-weighted MR images reflect paramagnetic deoxyhemoglobin, methemoglobin, or hemosiderin. MethodsIn 23 TSGCT patients (6 male and 17 females), the T2*MRI findings were analyzed. The tumor locations involved 10 large joints including nine knees and one ankle, 10 small joints including six fingers and four toes, as well as three wrists/hands. ResultsTen diffuse and 13 localized tumors were predominantly located in the large joints and small joints, respectively. The T2*-weighted images indicated three signal patterns of low, iso and high signal intensity compared to muscle. Low-, iso- and high-signal intensities were seen in 22 (96 %), 23 (100 %) and 12 (52 %) of the locations, respectively. To distinguish TSGCTs from the surrounding tissue, the low intensity T2*-weighted images and low to intermediate intensity T1-weighted images when compared to muscle and fluid, respectively were useful for the large joints. Low to intermediate intensity on T1- or T2-weighted images was useful to distinguish TSGCTs from subcutaneous tissue in the small joints. ConclusionsMRI using T2*-, as well as T1- and T2-weighted images, may be useful to detect lesions and assess the extent of TSGCTs in a tissue-specific manner, which is important for surgical planning.

Localized amyloidoma of the chest wall: diagnostic and surgical perspectives

BackgroundAn amyloidoma is defined as a solitary, localized, tumor-like deposit of amyloid in the absence of systemic amyloidosis. Amyloidomas occur most frequently in the bladder, followed by the lungs, trachea and bronchi, larynx and vocal cords, tonsils, conjunctivae, orbits, lymph nodes, gastrointestinal tract, and skin. It is extremely rare for an amyloidoma to present in the chest wall. Indeed, only 5 cases of chest wall amyloidoma have been reported. Moreover, all reported lesions were > 10 cm in size and involved the ribs. Herein, we report our experience with a patient who had a chest wall amyloidoma 3 cm in diameter without rib involvement.Case presentationA 3.1 × 1.5-cm tumor situated in the fifth intercostal space of the chest wall was found in an 83-year-old male during a routine health checkup. Chest magnetic resonance imaging showed a mass of intermediate intensity on T1-weighted imaging and low intensity on T2-weighted imaging with heterogeneous contrast enhancement. The tumor was resected during video-assisted thoracoscopic surgery. No adhesions were observed between the tumor and the lung. The tumor was white, hard, elastic, and located in the extrapleural fat without bone involvement. The tumor was removed in a piecemeal fashion because the tumor was fragile and the surgical margin was unclear. A wide resection was achieved, including the intercostal muscle. Pathologic examination of the tumor using Dylon and Congo red staining confirmed amyloid deposition with tumor spread from the fat to the intercostal muscle and vascular walls but no pleural invasion. Without clear evidence of systemic amyloidosis, this patient was diagnosed with an amyloidoma of the chest wall. The postoperative course was uneventful, and he is doing well 1 year after surgery.ConclusionAmyloidoma of the chest wall can present in various ways. An amyloidoma can be a small tumor, as in our patient, or the amyloidoma can be a large, destructive mass with rib involvement. Diagnosis of an amyloidoma should be kept in mind when patients present with chest wall tumors because an amyloidoma can be characterized by invasion within the chest wall independent of size.

CLDN6 CAR-T cell therapy of relapsed/refractory solid tumors ± a CLDN6-encoding mRNA vaccine: Dose escalation data from the BNT211-01 phase 1 trial using an automated product.

2518 Background: We are developing a chimeric antigen receptor (CAR)-T cell therapy targeting claudin 6 (CLDN6), an oncofetal antigen that is undetectable in healthy somatic tissue and highly expressed in various solid cancers. Autologous CLDN6 CAR-T cells are being tested alone and in combination with CLDN6-encoding CAR-T cell Amplifying RNA Vaccine (CARVac), a nanoparticulate RNA vaccine designed to stimulate and expand CLDN6 CAR-T cells. Methods: The ongoing first-in-human trial BNT211-01 evaluates the safety and feasibility of CLDN6 CAR-T cell transfer ± CARVac in lymphodepleted patients with relapsed/refractory solid tumors. Patients are pre-screened for CLDN6 expression with a cut-off of 50% positivity of intermediate or strong intensity by immunohistochemistry staining. Key endpoints are safety, tolerability, and anti-tumor activity. Pharmacokinetics of adoptively transferred CAR-T cells in peripheral blood is monitored by quantitative PCR. Dose escalation proceeds according to a classical 3+3 design, testing CLDN6 CAR-T cells at each dose level as both as monotherapy and in combination with CARVac. We previously reported results from 22 patients from 4 dose escalation cohorts with a manual CAR-T production process ± CARVac (ESMO-IO LBA38) which followed the same methodology. We observed durable responses along with a manageable safety profile, in line with commercial CAR-T products used to treat B-cell malignancies. No on-target/off-tumor toxicity and only a single case of (grade 1) neurotoxicity was observed. Given the encouraging efficacy, we have implemented an automated process to scale-up manufacturing. Accordingly, we are repeating the dose escalation with an automated CAR-T cell product, and with a modified CARVac regimen. As of 1st February 2023, 7 patients with epithelial ovarian carcinoma (EOC), 4 with testicular germ cell tumors (GCT), and a further 5 patients with tumors of various indications have been infused with CAR-T cells up to DL2. We intend to submit efficacy, safety and CAR T-cell pharmacokinetics data from 5 cohorts treated with 1x106, 1x107 or 1x108 CLDN6 CAR-T cells ± CARVac with a data cut-off of March 14th, 2023 from ≥17 treated patients as a late-breaking abstract. Clinical trial information: NCT04503278 .

SINGLE AGENT BRENTUXIMAB VEDOTIN AS BRIDGE TO ALLOGENEIC STEM CELL TRANSPLANT IN ADOLESCENTS WITH RELAPSED ANAPLASTIC LARGE CELL LYMPHOMA (ALCL): THE UCLH EXPERIENCE

Introduction: Optimal treatment for relapsed ALCL in children and adolescents is still subject of debate. We present here the results of our salvage strategy in the TYA Unit at UCLH, using single agent brentuximab vedotin (BV) as bridge to allogeneic stem cell transplant (alloHSCT). Methods: Between 2011 and 2021 we treated 7 patients with relapsed ALCL; all patients had received first line treatment according to ALCL99 guidelines. All relapses were biopsy proven and centrally reviewed if not performed at UCLH. Brentuximab Vedotin was given at the standard dose of 1.8mg/kg intravenously every 3 weeks. Results: All 7 patients were male; median age at diagnosis was 16 (range 13–19). Baseline characteristics were as follows: 7/7 were CD30+, 3/7 were CD3+, 6/7 biopsies were ALK positive, and 3/7 presented with a small cell/lymphohistiocitic (SC/LH) pattern. Six/7 patients had stage IV disease, 4/7 had skin involvement, bone marrow involvement was seen in 3/7 cases (infiltrate between 2 and 10%); 1/7 patients had bulky disease. Of the 7 patients, 3 had primary progressive disease, while 4/7 patients initially achieved a complete metabolic response (CMR), but had a very early relapse, between 2 and 3 months after completion of treatment. 6/7 patients received BV as first line of salvage treatment, 1 as second salvage, after failing ICM (ifosfamide, carboplatin, mitoxantrone), which was still our standard of care in 2011. Median number of doses of BV received was 3 (range 2–5); 6/7 (86%) patients obtained a complete metabolic remission, after a median of 3 doses (range 3–5). One patient progressed on BV; after failing crizotinib he achieved CMR with vinblastine-dexamethasone, then proceeded to transplant and is in long term remission. All 6 patients who achieved a complete remission after BV proceeded to alloHSCT, 1/6 from fully matched sibling donor, 3/6 from haploidentical donors, 2/6 from matched unrelated donors. Conditioning regimen was myeloablative for 5/6 patients, using Cyclophosphamide/total body irradiation +/- Campath depending on donor source; one patient received intermediate intensity conditioning with BEAM (BCNU, etoposide, cytarabine, melphalan)-Campath. With a median follow up of 55 months (range 4–133), all 6 patients are alive and 5/6 (83%) remain in remission with no need for further treatment; 1/6 patients relapsed 8 months post-transplant. This patient was re-challenged with BV, with the addition of donor lymphocytes infusions (DLI) and achieved a complete remission. Conclusions: Salvage treatment with single agent BV followed by alloHSCT is effective in adolescents with relapsed ALCL and lead to durable responses in a cohort of patients with high prevalence of high-risk features (advanced stage, SC/LH pattern, CD3+, early relapse after first line treatment). Interestingly, in one patient who relapsed after alloHSCT, BV and DLI were successful in inducing another complete remission. Keywords: Molecular Targeted Therapies, Non-Hodgkin (Pediatric, Adolescent, and Young Adult), Stem Cell Transplant No conflicts of interests pertinent to the abstract.

Impact of timing of prophylaxis commencement, F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A.

The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA). To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL). Thirty-eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non-null. Joint health and HRQoL were assessed with HJHS and EQ-5D-5L, respectively. The median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N=15, median age 26 years) and 31.5 years in the secondary group (N=22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p<.001), EQ-5D-5L index (0.9647 vs. 0.904, p=.022), EQ VAS (87 vs. 75, p=.01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p=.02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty-five null and thirteen non-null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non-null compared to null variants, respectively,with similar ABR and HJHS. Delayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non-null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.

Bird functional and taxonomic diversity in xerophytic forests: contributing to balance bird conservation and livestock production

Biodiversity is increasingly dependent on the ecological state of agricultural and livestock systems. Here, we assess the relationship between bird functional and taxonomic diversity and forest structure along a gradient in grazing intensity in xerophytic forests in Central-East Argentina. We found that bird functional diversity responds more to forest structure variables than taxonomic diversity. Further, we found a non-linear response of functional and taxonomic richness to grazing intensity, peaking at intermediate intensity. Mature forests with older trees and low grazing intensity favored a wider range of bird traits, such as seed dispersal and cavity nesters. In particular, taxonomic and functional diversity significantly increased with increasing canopy cover and DBH. In contrast, shrub encroachment, high grazing intensity, and the decrease of tree density and cover were associated with reduced functional diversity, affecting various nesting, foraging, and habitat requirements of birds. We recommend preserving high canopy cover and older trees and maintaining low grazing intensities to create a synergy between livestock production and biodiversity conservation.

Fibrosis entropy is associated with life-threatening arrhythmia in non-ischaemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ Trust and King’s College, the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC; WT088641/Z/09/Z). M.J.B. is supported by a Medical Research Council New Investigator Grant (MR/N011007/1) and British Heart Foundation (Project grant PG/18/74/34077). This work was supported by EPSRC 2018/19 DTP - EP/R513064/1 grant. This work was supported by a National Heart and Lung Institute Foundation grant awarded to Professor Sanjay Prasad and Dr Richard Jones. Background Enhanced risk stratification for implanted defibrillator requirement represents an important area of research in patients with non-ischemic cardiomyopathy (NICM). Myocardial fibrosis represents the major underlying arrhythmic substrate in this population, and its identification on late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is associated with life-threatening arrhythmia (LTA). Fibrosis entropy, a measure of scar texture heterogeneity, may confer important information regarding the underlying pro-arrhythmic mechanisms of both core scar and areas of intermediate signal intensity (Gray Zone [GZ]). Purpose We sought to: 1) evaluate whether LGE-CMR assessment of left ventricular (LV) tissue entropy had incremental utility to fibrosis presence for arrhythmic risk stratification of patients with NICM; 2) quantify the added utility of GZ entropy in such analysis. Methods This study involved a prospective observational cohort of consecutive patients with NICM and myocardial fibrosis detected on LGE-CMR. Epicardial and endocardial contours obtained from LGE-CMR data were used with a FWHM method to delineate core fibrosis (≥50% maximum signal intensity) and GZ fibrosis (≥35%-&amp;lt;50% signal intensity). Fibrotic masks were subsequently used, along with native dicom LGE-CMR images to compute tissue entropy, defined by the standard Shannon Entropy for core fibrosis, GZ fibrosis, and combined core+GZ fibrosis. Patients underwent adjudicated long-term follow-up for LTA (composite of sudden cardiac death, aborted sudden cardiac death or sustained ventricular tachycardia). Results Of 291 patients with NICM and mid-wall/subepicardial fibrosis, 38 patients (13.1%) experienced LTA over median follow-up of 6.3 years (interquartile range 4.6-9.1 years). On Cox regression analysis, core fibrosis entropy (Hazard ratio [HR] 1.77, 95% CI 1.25-2.54, p=0.001), GZ fibrosis entropy (HR 1.74, 95% CI 1.20-2.54, p=0.004) and combined fibrosis entropy (HR 1.98, 95% CI 1.30-2.52, p=0.001) were associated LTA after adjustment for variables used to guide ICD implantation (LVEF &amp;lt;35% and NYHA class &amp;gt;1) and remained associated in multivariable models accounting separately for core and GZ fibrosis mass. The addition of core fibrosis entropy, GZ fibrosis entropy and combined fibrosis entropy to a baseline clinical model improved the C-statistic from 0.49 to 0.59, 0.62 and 0.62, respectively. LVEF &amp;lt;35% was not associated with LTA (HR 1.45, 95% CI 0.77-2.74, p=0.25) on multivariable analysis. Conclusions Fibrosis entropy on LGE-CMR offers incremental utility to LVEF and fibrosis presence for arrhythmic risk prediction in patients with NICM. The combination of core and GZ fibrosis entropy offers the highest association with risk.

Light intensity changes and UVB radiation affect peridinin content and antioxidant activity in the Cassiopea andromeda holobiont

IntroductionThe up-side down jellyfish Cassiopea andromeda represents a yet untapped marine species that could be targeted as a new source for functional ingredients, such as natural pigments and antioxidants. Since C. andromeda hosts endosymbiotic dinoflagellates, this jellyfish contains peridinin pigments, which are linked with high antioxidant capacities and many other health-promoting properties. This study investigates the potential to specifically increase the content of peridinin and overall antioxidant activity in C. andromeda, through the targeted application of different photosynthetic active radiation (PAR) intensities and ultraviolet radiation, cultured in fully controlled indoor aquaculture systems.Materials and MethodsIndoor bred C. andromeda specimens were exposed to five different PAR intensities (50, 100, 200, 400 and 800 µmol photons m−2 s−1) and a combined treatment of narrow-band UVB (λ = 285 ± 10 nm) radiation and intermediate (200 µmol photons m−2 s−1) PAR intensity over a period of four weeks. Before the treatment and after two- and four-week treatment intervals, pigment concentrations and antioxidant activity levels were measured using high-performance liquid chromatography (HPLC) and the Trolox Equivalent AntioxidantCapacity (TEAC) assay, respectively. In addition, relative growth rate, umbrella pulsation and photosynthetic efficiency (measured by pulse amplitude modulated fluorometry) of C. andromeda individuals were also monitored throughout the experiment. ResultsChlorophyll a (Chl a) and peridinin (Per) dominated overall pigment content in C. andromeda endosymbionts, chlorophyll c2 and diadinoxanthin were detected in minor amounts. Over the treatment time, Chl a and Per concentrations, measured as µg g−1 jellyfish dry weight and pg microalgae-cell−1, decreased sharply at higher PAR intensities (200 – 800 µmol photons m−2 s−1) compared to the control treatment (100 µmol photons m−2 s−1). After four weeks Chl a and Per concentrations were lowest at the highest PAR intensity (800 µmol photons m−2 s−1) and highest at the lowest PAR intensity (50 µmol photons m−2 s−1). Moreover, the ratio of Chl a and Per showed a relative decrease of Per with increasing PAR intensity. The combined treatment of narrow-band UVB (λ = 285 ± 10 nm) radiation and intermediate (200 µmol photons m−2 s−1) PAR intensity led to significantly elevated Chl a and Per concentrations compared to the 200 µmol photons m−2 s−1 PAR treatment without UVB. Significantly elevated antioxidant activity levels, measured as Trolox Equivalents mmol g−1 jellyfish dry weight, were only detected in UVB exposed C. andromeda, indicating that Chl a and Per did not determine overall antioxidant capacity. The photosynthetic efficiency of C. andromeda endosymbionts was not affected by elevated antioxidant activity. Opposing that, the jellyfish hosts that were exposed to the UVB treatment shrunk drastically, indicating a strong stress response.DiscussionWith this study, we demonstrate for the first time the application potential of PAR intensity manipulations and UVB irradiation, to increase the content of valuable pigments and antioxidants in C. andromeda jellyfish and their endosymbiotic dinoflagellates that live in hospite within the host tissue. Based on these findings, we propose the culture of C. andromeda under fully controlled and light-optimized conditions as new pathway to harness bioproducts and functional ingredients.

Shade and no light explain Hovenia dulcis Thunb. invasiveness in subtropical forest fragments: A Greenhouse Microcosm Experiment

Hovenia dulcis is a non-native species with high capacity for invasion in subtropical forest fragments. In this study we used a greenhouse experiment simulating field abiotic and biotic conditions to investigate the germination and growth to determine the mechanisms associated with the high invasion potential of this species. We evaluated the effects of abiotic factors (light) and biotic factors (litter mass and litter type) on ecophysiological parameters: germination (GR), initial establishment (RR and ER) and shoot and root growth in a greenhouse experiment. Interactions between factors were compared using GLM, to select the best model and the factors that influence each parameter evaluated. GR, RR and ER were negative influenced by light intensities, when the low intensity presents more germination and establishment of individuals than intermediate intensity. Additionally, shoot height and root length were negatively influenced by the light intensity with a higher stem elongation in low light intensities. We found no interactions between the abiotic and biotic conditions tested. However, when evaluated individually, germination, establishment and growth were better in low light conditions regardless of the litter mass and litter type. These results challenge the classification of H. dulcis as an intolerant shade species.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

Menière's Syndrome Associated With Fibrous Dysplasia of the Temporal Bone.

Locally monochromatic two-step nonlinear trident process in a plane wave

In many-cycle plane waves at intermediate intensities, the nonlinear trident process can be well-approximated by the two sequential steps of nonlinear Compton scattering of a polarised real photon followed by its transformation into an electron-positron pair via nonlinear Breit-Wheeler pair creation. We investigate this two-step process in the intermediate intensity regime by employing the locally monochromatic approximation for each step and numerically evaluating resulting expressions. When photon polarisation is included, it is found to produce an order 10% decrease in the trident rate: the importance of polarisation increases at lower intensities, and decreases at higher intensities. Its importance persists at higher intensities in a linearly-polarised background, but disappears at high intensities in a circularly-polarised background. If the two steps are made to take place in two linearly-polarised plane wave pulses with perpendicular polarisations, the pair yield can be increased by approximately 30% compared to two plane waves with the same polarisation. It is also shown that harmonic structures in the Compton step can be passed to the pair step if the Compton edge is at an energy of the order of the threshold for linear Breit-Wheeler.

Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos) small and large intestine

Abstract. Susanti R, Utami NR, Yuniastuti A. 2023. Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos)small and large intestine. Biodiversitas 24: 2458-2466. The Microbiome composition could affect the duck's intestines' microenvironment, which may shape the microstructure's anatomy, metabolism, and immune system. Therefore, this study aims to characterize the intestinal microbiome's abundance, diversity, and IgA distribution in ducks' intestines. This study took 15 healthy domestic ducks (Anas platyrhynchosLinnaeus, 1758) from an intensive duck farm in Central Java, Indonesia. Five grams of each small and large intestine content were collected aseptically for metagenomic analysis. Then, the intestine organs were taken for immunohistochemistry preparations to depict the IgA distribution. The results showed that the small intestine has a greater bacterial abundance community, with 18 phyla, while only 13 are found in the large intestine. Interestingly, three phyla: Firmicutes, Actinobacteria, and Bacteroidetes, were found dominantly in both organs. However, the comparison of Firmicutes and Bacteroidetes ratio was higher in the small intestine (2357.76) than large intestine (10.64). The IgA distribution in the small and large intestines showed intermediate staining intensity (score: 2.07-2.20) and a final Allred score of 5.0 (positive). Even though dysbiosis microbiome was present in intestines with dominant species Streptococcus and Enterococcus, it seems no significant IgA over secretion. Understanding duck's gut immune response is important because it is highly tolerant to the pathogens that make them play an important role as an environmental reservoir for pathogenic viruses and bacteria and may potentially comprehend future infectious disease outbreaks.

Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT.

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning.

Extraction of effective sedimentary signals from rivers in Bangladesh and their application in the Bay of Bengal

River sediments compositions in Bangladesh were measured to extract effective signals of chemical weathering, sedimentary processes and provenances and applied to sedimentary record in the Bay of Bengal (BoB). Weathering indexes including the chemical index of alteration (CIA), weathering index of Parker (WIP), αAlE and related diagrams indicated overall weak to intermediate chemical weathering intensity in modern Ganges-Brahmaputra-Meghna (G-B-M) catchment. Sedimentary processes controlled sediment mineralogical and chemical composition to a certain extent, as reflected in the distinctions between suspended loads and bedloads. The suspended loads were richer in phyllosilicates than the bedloads in the Brahmaputra and the Meghna River sediments, and the Meghna River bedload exhibited sedimentary recycling and quartz dilution features. The Ganges River sediments showed multiple recycling and source mixing features. Extracted provenance proxies indicated that the Brahmaputra River sediments got relatively more effects from Himalayan mafic to intermediate rocks, while the Ganges River sediments indicate a mixture from the Himalaya and Indian Peninsula. more effects from ultramafic rocks were revealed for the Meghna River sediments. By comparing the extracted provenance proxies of different rivers and applying them to the identification of sediment sources in the Bay of Bengal (BoB), the Brahmaputra River is suggested to have been the primary supplier of sediments to the central-northern BoB since the last glacial period as a result of the highest erosion rate in the eastern syntaxis, which provides a new understanding of the sediment “source-sink” process in the BoB and indicates that effective extraction of fluvial information is crucial for marine sedimentology studies.

Noise-induced transitions in gene circuits: A perturbative approach for slow noise.

We consider a generic class of gene circuits affected by nonlinear extrinsic noise. To address this nonlinearity we introduce a general perturbative methodology based on assuming timescale separation between noise and gene dynamics, with fluctuations exhibiting a large but finite correlation time. We apply this methodology to the case of the toggle switch, and by considering biologically relevant log-normal fluctuations, we find that the system exhibits noise-induced transitions. The system becomes bimodal in regions of the parameter space where it would be deterministically monostable. We show that by including higher order corrections our methodology allows one to obtain correct predictions for the occurrence of transitions even for not so large correlation time of the fluctuations, thereby overcoming limitations of previous theoretical approaches. Interestingly we find that at intermediate noise intensities the noise-induced transition in the toggle switch affects one of the genes involved, but not the other one.

A machine learning model for predicting progressive crack extension based on experimental data obtained using DCPD measurement technique

A series of low cycle fatigue loading experiments were performed, using Inconel 718 (IN718) superalloy, to produce time history data using Direct Current Potential Drop (DCPD) approach at a range of temperatures and it was used to train a Bidirectional Long-Short Term Memory Neural Network (BiLSTM) model. The experimental investigations were conducted to understand the statistical nature of crack jumps during the fatigue loading. The BiLSTM model was trained on high sampling rate experimental data from crack initiation up through the Paris regime. For a single sample, the trained machine learning model was able to predict future crack events based on prior crack jumps in the time history. The model was able to predict the progressive crack extension at intermediate temperatures and stress intensities that lie between experimental conditions. The BiLSTM model demonstrated the potential to be used as a tool for future investigation into fundamental mechanisms such as high-temperature oxidation at the crack tips.

Measuring the input rank in global supply networks

AbstractWe introduce the Input Rank as a network measure of relevance of direct and indirect suppliers in Global Value Chains. We conceive an intermediate input to be more relevant for a downstream buyer if a negative shock to that input's productivity affects that buyer more. In particular, in our framework, the relevance of any input depends on: (i) the network position of the supplier relative to the buyer, (ii) the patterns of intermediate input intensities connecting the buyer and the supplier, and (iii) the competitive pressures along supply chains. After we compute the Input Rank from both the U.S. and the world input–output tables, we provide useful insights into the crucial role of services inputs as well as on the relatively higher relevance of domestic suppliers, and suppliers coming from regionally integrated partners. Finally, we test that the Input Rank is a good predictor of vertical integration choices made by 20,489 U.S. parent companies controlling 154,836 subsidiaries worldwide.

How can we differentiate supratentorial tumor recurrence from postradiation imaging changes in children treated for primary malignant brain tumors?

Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

How many patients do we need? Predictors of consent to participate in clinical research studies in orthopaedic trauma.

To characterize the recruitment rates at a level-I trauma center enrolling for multiple prospective orthopedic trauma research studies and identify patient and study-related predictors of consent. We conducted a case control study to identify predictors of study consent. The authors categorized studies based on intensity of the study intervention (Low, Intermediate, or High). A 2-level generalized linear model with random intercept for study was used to predict study consent. This analysis includes data from ten federally funded studies conducted as part of a large, national consortium that were enrolling patients in 2013-2014.Patients/Participants: 334 patients were approached for at least one study and included in the analysis. N/A. Consent to participate in the research study. A total of 315 patients consented to be in a study (71% of approached patients). Consent rate varied by study (45-95%). No patient characteristics (race, age, or gender) were associated with consent. Patients approached for studies of intermediate intensity were 83% less likely to consent (OR=0.17; 95% CI: 0.04, 0.67), and those approached for studies of high intensity were 91% less likely to consent (OR=0.09; 95% CI: 0.03, 0.32). Patient factors were not associated with consent. Study intensity is a major driver of consent rates. Studies of higher intensity will require the study team to approach up to twice as many patients as the target enrollment. This study provides a framework that can be used in study planning and determination of feasibility. Level III. See Instructions for Authors for a complete description of levels of evidence.