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We present a novel thermodynamic parameter estimation framework for energy-based surgery on live tissue, with direct applications to tissue characterization during electrosurgery. This framework addresses the problem of estimating tissue-specific thermodynamics in real-time, which would enable accurate prediction of thermal damage impact to the tissue and damage-conscious planning of electrosurgical procedures. Our approach provides basic thermodynamic information such as thermal diffusivity, and also allows for obtaining the thermal relaxation time and a model of the heat source, yielding in real-time a controlled hyperbolic thermodynamics model. The latter accounts for the finite thermal propagation time necessary for modeling of the electrosurgical action, in which the probe motion speed often surpasses the speed of thermal propagation in the tissue operated on. Our approach relies solely on thermographer feedback and a knowledge of the power level and position of the electrosurgical pencil, imposing only very minor adjustments to normal electrosurgery to obtain a high-fidelity model of the tissue-probe interaction. Our method is minimally invasive and can be performed in situ. We apply our method first to simulated data based on porcine muscle tissue to verify its accuracy and then to in vivo liver tissue, and compare the results with those from the literature. This comparison shows that parameterizing the Maxwell--Cattaneo model through the framework proposed yields a noticeably higher fidelity real-time adaptable representation of the thermodynamic tissue response to the electrosurgical impact than currently available. A discussion on the differences between the live and the dead tissue thermodynamics is also provided., Accepted for publication in the IEEE Transactions on Biomedical Engineering. Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB029766

Anatabine and anabasine are two tobacco alkaloids used to differentiate between tobacco users and abstainers, including users of nicotine replacement therapy. Cutoff values (>2 ng/mL for both alkaloids) have not been revised since their implementation in 2002. These values may be too high, leading to increased likelihood of misclassification between smokers and abstainers. This results in major consequences, especially adverse outcomes of transplantation when smokers were incorrectly identified as being abstinent. This study proposes that a lower threshold for anatabine and anabasine will better distinguish tobacco users from non-users and thereby improve patients' care. A new and more sensitive analytical method by liquid chromatography-mass detection was developed to allow the quantification of low concentrations. Anatabine and anabasine were measured in urine samples of 116 self-reported daily smokers and 47 long-term non-smokers (confirmed by the analysis of nicotine and its metabolites). The best compromise between sensitivity and specificity allowed us to determine new cutoff values. The thresholds >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine were associated with a sensitivity of 97% (anatabine) and 89% (anabasine) and a specificity of 98% for both alkaloids. These cutoff values greatly increased the sensitivity given that it dropped to 75% (anatabine) and 47% (anabasine) when using the reference value (>2 ng/mL). The cutoff values >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine appear to better differentiate tobacco users from abstainers than the current reference threshold (>2 ng/mL for both alkaloids). It may considerably impact patients' care, especially in transplantation settings in which smoking abstinence is essential to avoid adverse outcomes of transplantation.

Resource availability is a key factor driving marine bird movements and distributions, but direct information on prey availability is difficult to obtain at relevant scales. We present novel methods for describing multi-scale trophic associations, combining movement analyses of marine birds with estimates of forage fish surface aggregations from digital aerial survey data and species occupancy from bottom trawl survey data. We analyzed satellite telemetry data from northern gannets Morus bassanus, red-throated loons Gavia stellata, and long-tailed ducks Clangula hyemalis in the US Atlantic during the non-breeding period. Using discrete-time hidden Markov models to distinguish area-restricted (i.e. putative foraging) from transit movements, we examined how environmental factors influence movement, and how forage fish species distributions and surface aggregations influence habitat use by gannets and loons that have greater dietary reliance. Our results suggest that chlorophyll a concentration significantly affected movement behavior across species, highlighting the importance of higher-productivity areas around estuaries during colder months when regional productivity is low. Though variable across species and seasons, spatial cross-correlation analysis revealed that herring species (Family Clupeidae), including Atlantic menhaden Brevoortia tyrannus, may be important resources; it also showed positive spatial correlations with forage fish aggregations. This suggests that prey patch dynamics and factors driving aggregation formation may be as important as species composition. However, spatial patterns were generally low (

Purpose Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. Methods From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. Results 144 Patients were identified. The median age was 62 (23–90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p

PURPOSE: The use of virtual care rapidly increased during the COVID-19 pandemic and has persisted as a routine method of care delivery. Much of the literature on virtual care in oncology has focused on solid tumors, and little is known about its application in malignant hematology. METHODS: We performed a retrospective review of patients with hematologic malignancies at Princess Margaret Cancer Centre from October 2019 to March 2021 to determine the use of virtual care during this period, cost-savings associated with virtual visits, and patient satisfaction. Patient satisfaction was assessed using the Your Voice Matters survey, a provincially administered survey to evaluate patient experience. RESULTS: Overall, 12.1% (1,122/9,295) of patients had a virtual visit during the study period (0% from October 2019 to February 2020, 36% from March to August 2020, and 30% from September 2020 to March 2021), of which 36% were in the lymphoma clinic and 46% were in the myeloma clinic. The mean two-way opportunity cost for an in-person visit was $168.00 CAD per person with public transit, and $120.40 CAD per person driving. Responses to the Your Voice Matters survey indicated that patients with a virtual visit reported that physical symptoms were discussed appropriately (mean 4.73/5), and were more likely to ask for a follow-up virtual visit compared with patients with in-person visits (mean 4.50/5 v 3.02/5, respectively; P < .01). CONCLUSION: These findings suggest that virtual care may be a feasible and well-received tool for delivering care to a substantial proportion of patients with hematologic malignancies, while enabling substantial cost-savings to patients.

This study aimed to evaluate the development of healthcare teamwork during and after the collaboration tabletop exercises, through observation and interview methods. Integration and maturity theoretical models were employed to explain the collaborative challenges in teams that may suffer from unequally distributed power, hierarchies, and fragmentation. Using three-level collaboration tabletop exercises and the Command and control, Safety, Communication, Assessment, Treatment, Triage, Transport (CSCATTT) instrument, 100 healthcare workers were observed during each step in the implementation of the CSCATTT instrument using two simulated scenarios. The results show a lack of integration and team maturity among participants in the first scenario, leading to the delayed start of the activity, task distribution, and decision making. These shortcomings were improved in the second scenario. In-depth interviews with 20 participants in the second phase of the study revealed improved knowledge and practical skills, self-confidence, and ability in team building within trans-professional groups in the second scenario, which in concordance with the integration theory, was due to the attempts made in the first scenario. Additionally, there was an improvement in the team’s maturity, which in concordance with the maturity theory, was due to the knowledge and practical skills during scenario plays. These results indicate the importance of continuous tabletop training, and the use of CSCATTT as a collaborative instrument, to promote the development of collaboration and to test the concept of preparedness.

A learning tool in the form of LKPD is essential in learning activities because LKDP measures students' original abilities from learning activities with a certain learning approach. The implementation of this service is motivated by the lack of knowledge and experience of elementary school teachers in developing LKPD and integrating it with culture. This service aims to provide the expertise and ability of teachers to develop tools and integrate them with culture. The service is carried out by giving workshops to Cluster 3 Se District of Bukit Raya teachers. The service results showed that all teachers were enthusiastic about participating in the activities. This is evidenced by several teachers who immediately asked questions during the service process. The teacher asked if all subjects could be integrated with Malay culture. In addition, the teacher asked what steps need to be taken to develop or design LKPD based on Riau Malay culture. Abstrak Perangkat pembelajaran berupa LKPD sangat penting dalam kegiatan pembelajaran karena LKDP mengukur kemampuan asli siswa dari kegiatan pembelajaran dengan pendekatan pembelajaran tertentu. Pelaksanaan pengabdian ini dilatarbelakangi oleh minimnya pengetahuan dan pengalaman guru SD dalam mengembangkan LKPD dan mengintegrasikannya dengan budaya. Layanan ini bertujuan untuk memberikan keahlian dan kemampuan guru untuk mengembangkan perangkat dan mengintegrasikannya dengan budaya. Pengabdian dilakukan dengan memberikan workshop kepada guru-guru Gugus 3 Se Kecamatan Bukit Raya. Hasil pengabdian menunjukkan semua guru antusias mengikuti kegiatan. Hal ini dibuktikan dengan beberapa guru yang langsung bertanya pada saat proses pelayanan. Guru menanyakan apakah semua mata pelajaran bisa diintegrasikan dengan budaya melayu. Selain itu, guru menanyakan langkah-langkah apa yang perlu dilakukan untuk mengembangkan atau merancang LKPD berbasis budaya Melayu Riau.

Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear.This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression.Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38).In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

OBJECTIVE To determine the pharmacokinetics of a single bolus of intravenous (IV) propofol after intramuscular administration of etorphine, butorphanol, medetomidine, and azaperone in 5 southern white rhinoceros to facilitate reproductive evaluations. A specific consideration was whether propofol would facilitate timely orotracheal intubation. ANIMALS 5 adult, female, zoo-maintained southern white rhinoceros. PROCEDURES Rhinoceros were administered etorphine (0.002 mg/kg), butorphanol (0.02 to 0.026 mg/kg), medetomidine (0.023 to 0.025 mg/kg), and azaperone (0.014 to 0.017 mg/kg) intramuscularly (IM) prior to an IV dose of propofol (0.5 mg/kg). Physiologic parameters (heart rate, blood pressure, respiratory rate, and capnography), timed parameters (eg, time to initial effects and intubation), and quality of induction and intubation were recorded following drug administration. Venous blood was collected for analysis of plasma propofol concentrations using liquid chromatography-tandem mass spectrometry at various time points after propofol administration. RESULTS All animals were approachable following IM drug administration, and orotracheal intubation was achieved at 9.8 ± 2.0 minutes (mean ±SD) following propofol administration. The mean clearance for propofol was 14.2 ± 7.7 ml/min/kg, the mean terminal half-life was 82.4 ± 74.4 minutes, and the maximum concentration occurred at 2.8 ± 2.9 minutes. Two of 5 rhinoceros experienced apnea after propofol administration. Initial hypertension, which improved without intervention, was observed. CLINICAL RELEVANCE This study provides pharmacokinetic data and insight into the effects of propofol in rhinoceros anesthetized using etorphine, butorphanol, medetomidine, and azaperone. While apnea was observed in 2 rhinoceros, propofol administration allowed for rapid control of the airway and facilitated oxygen administration and ventilatory support.

Safe and effective vaccines are available that provide strong immunity to our body to produce specific protection against some of the dangerous disease. Protection of the child from COVID 19 disease Billions of people have been vaccinated against COVID-19. Getting vaccinated is one of the most important things you can do to protect yourself against COVID-19, help end the pandemic and stop new variants emerging. COVID 19 viral disease and affect the lungs.Research Approach:- The quantitative approach was used to determine the effectiveness of self-instructional module on knowledge and attitude regarding covid-19 vaccination on among mothers of 12 to 18 year children. Research Design:- The research design used in this study was quasi experimental one group pre test post test design is used to determine the effectiveness of self-instructional module on knowledge and attitude regarding covid-19 vaccination before and after the self-instructional module among mothers of 12 to 18 year children. Setting: The study was conducted selected rural area Bavliya Khurd. It is situated 3 km away from Index Nursing College, Indore. Sample Size: Sample size of this study consists of 100 mothers of 12 to 18 year children living in selected community area at bavliya khurd. Sampling Technique: Purposive sampling technique was used to select the sample. Sample were collected, who fulfill the sampling criteria are included in this study.The frequency and percentage distribution of samples according to the pre test knowledge score of mothers regarding covid-19 vaccination. It revealed that 40(40%) mothers had Poor knowledge, and 59(59%) mothers had Average knowledge and 01(01%) mother had Good knowledge about covid-19 vaccination. The frequency and percentage distribution of samples according to the post test knowledge scores of mothers regarding covid-19 vaccination. It revealed that 00 (00%) mothers had Poor knowledge, 80(80.%) mothers had Average knowledge,20(20%) mothers had Good knowledge about covid-19 vaccination. the frequency and percentage distribution of samples according to the pre test attitude score of mothers regarding covid-19 vaccination. It revealed that 21(21%) mothers had Very poor attitude, and 55(55%) mothers had Poor attitude about covid-19 vaccination, 21(21%) mothers had Faire attitude and 03(03%) mothers had Good attitude about covid-19 vaccination, 00(00%) mothers had Excellent attitude. The table-III shows that the frequency and percentage distribution of samples according to the pre test attitude score of mothers regarding covid-19 vaccination. It revealed that 02 (02%) mothers had Very poor attitude, and 44 (44%) mothers had Poor attitude about covid-19 vaccination, 40 (40%) mothers had Faire attitude and 13 (13%) mothers had Good attitude about covid-19 vaccination, 01 (01%) mothers had excellent attitude.The self-instructional module through booklet found to be very effective in improving the knowledge and attitude among mothers who have 12 to 18 yrs children on covid-19 vaccination. The knowledge and attitude regarding covid-19 vaccination was improved by health teaching through booklet. Being as a nurses, our main responsibility is try to make our India, free from communicable disease by providing covid-19 vaccination for all 12 to 18 year children.

The membrane proteins are essential targets for understanding cellular function. The unbiased identification of membrane protein targets is still the bottleneck for a system-level understanding of cellular response to stimuli or perturbations. It has been suggested to enrich the soluble proteome with membrane proteins by introducing nonionic surfactants in the solubilization solution. This strategy aimed to simultaneously identify the globular and membrane protein targets by thermal proteome profiling principles. However, the thermal shift assay would surpass the cloud point temperature from the nonionic surfactants frequently utilized for membrane protein solubilization. It is expected that around the cloud point temperature, the surfactant micelles would suffer structural modifications altering protein solubility. Here, we show that the presence of nonionic surfactants can alter protein thermal stability from a mixed, globular, and membrane proteome. In the presence of surfactant micelles, the changes in protein solubility analyzed after the thermal shift assay was affected by the thermally dependent modification of the micellar size and its interaction with proteins. We demonstrate that the introduction of nonionic surfactants for the solubilization of membrane proteins is not compatible with the principles of target identification by thermal proteome profiling methodologies. Our results lead to exploring thermally independent strategies for membrane protein solubilization to assure confident membrane protein target identification. The proteome-wide thermal shift methods have already shown their capability to elucidate mechanisms of action from pharma, biomedicine, analytical chemistry, or toxicology, and finding strategies, free from surfactants, to identify membrane protein targets would be the next challenge. This work has been performed with funding from the ERA-NET Marine Biotechnology project CYANOBESITY, which is cofounded by FORMAS, Sweden, grant no. 2016-02004 (S.C.); the project GOLIATH that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 825489 (S.C.); IKERBASQUE, Basque Foundation for Science (S.C.); Basque Government Research Grant IT-971-16 and IT-476-22 (S.C.); Magnus Bergvalls Foundations (S.C.), VINNOVA No 2021-04909 (S.C.), and the grant for doctoral studies OAICE-75-2017 World Bank counterpart - University of Costa Rica (V.L.-F.).

The history of Black performance in Canada goes back to the early nineteenth century alongside blackface. In the late twentieth century, ‘blind casting’ became an opportunity for Black performers to work on canonical works of Western theatre. But this form of casting is problematic as it asks the audience to look beyond the identity of the performer, to disregard any important facet of their humanity. As casting is evolving to acknowledge the identity of the performers, some cases show that cultural casting demands additional human and financial resources so that the work is precise and culturally accurate. A deft use of conscious casting can lead to more layered and additional aesthetic complexity to play in the repertoire. A judicious application of our new paradigms in culturally specific and safer spaces should not be construed as dogma; in fact, there are occasions where we must subvert our thinking for greater artistic results and compassionate treatment of performers. Lenity and mindfulness in casting will guide casting directors and institutional dramaturges, and this will yield better artistic results.

In the song, of course, there is a deep meaning from the songwriter. Lyrics as one of the elements of the song, it contains an outpouring of personal feelings and a series of words that are often influenced by the values ??of a culture, social, or moral. This study seeks to examine and describe the moral values ??contained in the song lyrics of Rachel Platten. This study aims to describe the types and characteristics of the moral values ??of the songs “Fight Song”, “Stand by You”, “Broken Glass”, and “Soldiers”. The method used in this research is qualitative method. The data in this study are verbal in the form of words, phrases or sentences contained in the lyrics of songs by Rachel Platten, which are adapted to the purpose of the study. The next step is data collection. It’s the procedure of collecting and measuring. Also, the procedure of analyzing accurate insights for research using standard validated techniques. Data analysis includes data reduction, data presentation, and conclusion drawing and data verification. The results showed that in the lyrics of the songs are kinds and characteristics of moral value. Keywords: Characteristics of Moral Value, Kinds of Moral Value, Rachel Platten, Songs Lyric

Over the past decade, multiple trials, including the precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of the cancer histology. Although many therapies are now approved for the treatment of cancers harboring specific genomic alterations, most patients do not respond to therapies targeting a single alteration. Further, when antitumor responses do occur, they are often not durable due to the development of drug resistance. Therefore, there is a great need to identify rational combination therapies that may be more effective. To address this need, the NCI and National Clinical Trials Network have developed NCI-ComboMATCH, the successor to NCI-MATCH. Like the original trial, NCI-ComboMATCH is a signal-seeking study. The goal of ComboMATCH is to overcome drug resistance to single-agent therapy and/or utilize novel synergies to increase efficacy by developing genomically-directed combination therapies, supported by strong preclinical in vivo evidence. Although NCI-MATCH was mainly comprised of multiple single-arm studies, NCI-ComboMATCH tests combination therapy, evaluating both combination of targeted agents as well as combinations of targeted therapy with chemotherapy. Although NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. Although NCI-MATCH consisted of single-arm studies, ComboMATCH utilizes single-arm as well as randomized designs. NCI-MATCH had a separate, parallel Pediatric MATCH trial, whereas ComboMATCH will include children within the same trial. We present rationale, scientific principles, study design, and logistics supporting the ComboMATCH study.

Purpose: The spatiotemporal index (STI) is a standard metric for quantifying the stability and patterning of speech movements. The STI has often been applied to individual speech articulators, but an STI derived from the acoustic signal offers a composite and easily obtained measure that incorporates multiple components of the speech production complex. In this work, we examine the relationship between kinematic and acoustic STIs in children with and without developmental language disorder (DLD), with the aim of determining whether the acoustic and kinematic STIs reflect similar degrees of production variability. Method: A total of 85 children with DLD and with typical language development (or typically developing [TD] children), aged 4–8 years, were studied. In this methodological article, two experiments were conducted: one deliberately selected because group differences were observed in the kinematic STI (i.e., sentence production) and one in which there were no group differences in the kinematic STI (i.e., nonword production). These two experiments are representative of speech stability studies. The aim was to determine whether the acoustic STI (i.e., amplitude envelope) results aligned with those obtained via the kinematic STI (i.e., lip motion). Results: In sentence production, most group differences aligned across kinematic and acoustic STI measures. The acoustic, but not the kinematic, STI showed higher variability in children with DLD compared with the 6-year-old TD group. In nonword production, neither the kinematic STI nor the acoustic STI differentiated children with DLD from TD children. In each experiment, the kinematic and acoustic STIs showed a moderate-to-strong correlation. Conclusions: The kinematic and acoustic STIs assess different components of speech movement patterning. However, the relationship between acoustic and kinematic spatiotemporal stability is strong in two tasks of varying linguistic complexity in children with and without DLD. These findings are promising for future experimental work in this area.

There is no formalized communication curriculum for surgical training. The aim of this study is to determine the benefit of annual communication skill-building workshops for surgical residents over several years.The general surgery and the integrated cardiothoracic surgery residents in a tertiary care, urban academic center participated in a 2-hour communication skill-building workshop each year from July 2017 to June 2021. Each participant was administered an anonymous pre-session and post-session survey with a 5-point Likert scale to assess their self-reported preparedness and their evaluation of the workshop. Survey responses were divided into three groups based on their experience in this workshop; no experience (Experience 0), 1 y of experience (Experience 1), and two or more years of experience (Experience 2+). They were compared among groups.Seventy-one surgical residents participated in the workshop generating 124 survey results (Experience 0, 71 [57.3%], Experience 1, 41 [33.1%], and Experience 2+, 12 [9.7%]). Self-reported preparedness scores improved for the overall group as well as for each experience group. While scores decreased significantly in the following years, they improved after each workshop. Scores were significantly better with more experience (4, interquartile range [IQR] 3-4 in Experience 0, 4, IQR 3-5 in Experience 1, 4, IQR 4-5 in Experience 2+, P 0.001 between Experience 0 and Experience 1, P = 0.041 between Experience 1 and Experience 2+). All residents reported an overwhelmingly positive review of the curriculum.Yearly 2-hour communication skills practice increased surgical residents' self-reported preparedness, and the repetition helped the improvement. Annual workshops are important for residents to be more prepared for serious illness communication.

Background & Aims:CD4+CD25+Foxp3+regulatory T cells (Tregs) are essential to maintain immunological tolerance and have been shown to promote liver allograft tolerance in both rodents and humans. Low-dose IL-2 (LDIL-2) can expand human endogenous circulating Tregsinvivo, but its role in suppressing antigen-specific responses and promoting Treg trafficking to the sites of inflammation is unknown. Likewise, whether LDIL-2 facilitates the induction of allograft tolerance has not been investigated in humans. Methods:We conducted a clinical trial in stable liver transplant recipients 2–6 years post-transplant to determine the capacity of LDIL-2 to suppress allospecific immune responses and allow for the complete discontinuation of maintenance immunosuppression (ClinicalTrials.govNCT02949492). One month after LDIL-2 was initiated, those exhibiting at least a 2-fold increase in circulating Tregs gradually discontinued immunosuppression over a 4-month period while continuing LDIL-2 for a total treatment duration of 6 months. Results:All participants achieved a marked and sustained increase in circulating Tregs. However, this was not associated with the preferential expansion of donor-reactive Tregs and did not promote the accumulation of intrahepatic Tregs. Furthermore, LDIL-2 induced a marked IFNγ-orchestrated transcriptional response in the liver even before immunosuppression weaning was initiated. The trial was terminated after the first 6 participants failed to reach the primary endpoint owing to rejection requiring reinstitution of immunosuppression. Conclusions:The expansion of circulating Tregs in response to LDIL-2 is not sufficient to control alloimmunity and to promote liver allograft tolerance, due, at least in part, to off-target effects that increase liver immunogenicity. Our trial provides unique insight into the mechanisms of action of immunomodulatory therapies such as LDIL-2 and their limitations in promoting alloantigen-specific effects and immunological tolerance. Clinical Trials Registration:The study is registered at ClinicalTrials.gov (NCT02949492). Impact and implications:The administration of low-dose IL-2 is an effective way of increasing the number of circulating regulatory T cells (Tregs), an immunosuppressive lymphocyte subset that is key for the establishment of immunological tolerance, but its use to promote allograft tolerance in the setting of clinical liver transplantation had not been explored before. In liver transplant recipients on tacrolimus monotherapy, low-dose IL-2 effectively expanded circulating Tregs but did not increase the number of Tregs with donor specificity, nor did it promote their trafficking to the transplanted liver. Low-dose IL-2 did not facilitate the discontinuation of tacrolimus and elicited, as an off-target effect, an IFNγ-orchestrated inflammatory response in the liver that resembled T cell-mediated rejection. These results, supporting an unexpected role for IL-2 in regulating the immunogenicity of the liver, highlight the need to carefully evaluate systemic immunoregulatory strategies with investigations that are not restricted to the blood compartment and involve target tissues such as the liver.

To report acute toxicity and health-related quality of life (HRQoL) outcomes of a phase II clinical trial of magnetic resonance imaging (MRI)-guided prostate high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy.Patients with intermediate- and high-risk prostate cancer (PCa) were eligible. Treatment consisted of a single 15 Gy MRI-guided HDR-BT followed by external beam radiotherapy (37.5-46 Gy depending on their risk category). Dosimetry, toxicity and HRQoL outcomes were collected prospectively at baseline, 1 and 3 months using Common Terminology Criteria for Adverse Events Version 4.0 and the expanded PCa index composite, respectively. General linear mixed modeling was conducted to assess the changes in expanded PCa index composite domain scores over time. A minimally important difference was defined as a deterioration of HRQoL scores at 3 months compared to baseline ≥ 0.5 standard deviation. A p value ≤ 0.05 was considered statistically significant.Sixty-one patients were included. Acute grade (G)2 urinary toxicity was observed in 18 (30%) patients while 1 (2%) patient had G3 toxicity, and none had G4 toxicity. Two patients had an acute urinary retention. G2 gastrointestinal toxicity was reported by 5 (8%) patients with no G3-4. Compared to baseline, urinary HRQoL scores significantly declined at 1 month (p0.001) but recovered at 3 months (p0.05). Bowel (p0.001) and sexual (p0.001) domain scores showed a significant decline over the 3-month follow-up period. At 3 months, 44%, 49% and 57% of patients reported a minimally important difference respectively in the urinary bowel and sexual domains.MRI-guided HDR-BT boost is a safe and well tolerated treatment of intermediate- and high-risk PCa in the acute setting. A longer follow-up and a comparison to ultrasound-based HDR-BT are needed to assess the potential benefit of MRI-guided prostate HDR-BT.

A new NLO crystal of L-Arginine doped with potassium iodide were harvested from solution growth technique with slow evaporation method. Powder X-ray diffraction analysis exposes the structure. Presence of vibration functional groups in the grown crystal was confirmed by FTIR spectroscopy. Using the spectrum of UV–Vis-NIR the optical transmission and absorption spectra were studied. TGA-DSC studies reveal the decomposition and thermal stabilities of the grown crystals. Kurtz Perry Powder technique determines the second harmonic generation NLO behavior.

Sodium succinate a semi organic single crystal was grown by solution growth slow evaporation method taking water as solvent. Identification of functional groups was done through the spectral FTIT studies. The transparency of the sodium succinate was confirmed by UV–Vis-NIR spectral analysis. To check the thermal stability and to confirm the melting point of the grown crystal, TGA-DSC studies were taken. Using Nd-YAG Q-switched laser with wavelength (1064 nm) the laser damage threshold was measured.

This study was conducted to elucidate the uses of chitosan extracted from Penaeus monodon. Chitosan is a natural polysaccharide that shapes structural additives inside the exoskeleton of crustaceans. In this research, chitin and chitosan had been extracted from the Penaeus monodon exoskeleton via the chemical system through a series of steps which include demineralization, deproteinization, and deacetylation. The chitosan received by the deacetylation system turned into analyzed for biochemical parameters like protein, lipid, carbohydrate, ash, moisture, degree of deacetylation, water binding capacity (WBC), fats binding capacity (FBC), and solubility. The statistics show that chitin contains 3.82% protein, 1.24% lipid, 68.45% carbohydrate, 2.9% ash, 9.6% moisture content, 67.60% DD, 640% WBC, 420% FBC, and 99% solubility which were higher than chitosan. The textile effluent was treated with extracted chitosan and chitosan membrane for 30 days. Maximum decolourization (55.56 to 95.75%) of the effluent occurs with 2 g of chitosan. This study concluded that chitosan is a promising absorbent for removing colour from textile effluent.

A huge mainshock activates several aftershocks, divulging the public to serious risk and impeding building repair, rehabilitation, and restoration works. The performance of a structure during multiple earthquakes depends on structural properties and the characteristics of ground motion. Hence, the selection of seismic sequence plays a vital role in the analysis. Presumption of spatial and temporal characteristics of aftershocks is needed for the identification of these repeated motions. This paper further looks into statistical variability connected with aftershock sequences. A critical review of different real and artificial seismic sequences taken for the analysis is carried out. A few studies reveal that a strong motion database for procuring actual mainshock aftershock sequences could underrate the aftershock effects as the database is inadequate and imperfect. It is also observed that artificial sequences can take the place of real sequences especially when an ample data set of real mainshock aftershock sequences are not accessible.

The research objective was to describe what and how classroom interaction patterns and what factors influenced English teacher candidates in micro-teaching. The research problem was what and how classroom interaction patterns and what factors they make in the performance of the basic skill. The research method used was qualitative research. The researchers used videotape and in-depth interviews as the research instruments to collect the data needed. The total respondents were 66 students as English teacher candidates. The results and important findings from the videos were obtained that the English teacher candidates had good, good enough, enough, and bad classroom interaction patterns. In group work, the interaction between student and student was bad. A similar thing happened in closed-ended teacher questioning, the interaction between student-teacher-student was bad too meanwhile in open-ended teacher questioning was good enough. In the choral response, the interaction pattern between student-content was good. The last was teacher talks, the interaction pattern of student-teacher was enough. Some factors influenced classroom interaction patterns such as the result from the in-depth interview that were the linguistic ability level of English teacher candidates, ability to select interesting topics, ability to master the content, ability to manage the classroom, and lack of confidence. In a conclusion, classroom interaction patterns were at different levels influenced by some factors, monotonous and mostly similar patterns for all the English teacher candidates as happened in a conventional classroom.

Hippocampal adult neural stem cells emerge from progeny of the neuroepithelial lineage during murine brain development. Hippocampus development is increasingly well understood. However, the clonal relationships between early neuroepithelial stem cells and postnatal neurogenic cells remain unclear, especially at the single-cell level. Here we report fate bias and gene expression programs in thousands of clonally related cells in the juvenile hippocampus based on single-cell RNA-seq of barcoded clones. We find evidence for early fate restriction of neuroepithelial stem cells to either neurogenic progenitor cells of the dentate gyrus region or oligodendrogenic, non-neurogenic fate supplying cells for other hippocampal regions including gray matter areas and the Cornu ammonis region 1/3. Our study provides new insights into the phenomenon of early fate restriction guiding the development of postnatal hippocampal neurogenesis.