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Objectives: This study aimed to (1) estimate the total pool of neonatal therapists (occupational therapists, physical therapists, and speech-language pathologists who work in the neonatal intensive care unit [NICU]) and the average number represented in each U.S. based NICU, and (2) investigate the relationships between the number and type of neonatal therapy team members to NICU/hospital, population, and therapy factors., Study Design: This study used several methods of data collection (surveys, phone calls, and web site searches) that were combined to establish a comprehensive list of factors across each NICU in the United States., Results: We estimate that there are 2,333 full-time equivalent (FTE) positions designated to neonatal therapy coverage, with 4,232 neonatal therapists covering those FTEs. Among 564 NICUs with available neonatal therapy staffing data, 432 (76%) had a dedicated therapy team, 103 (18%) had pro re nata (as the circumstances arise; PRN) therapy coverage only, and 35 (6%) had no neonatal therapy team. Having a dedicated therapy team was more likely in level-IV ( n  = 112; 97%) and -III ( n  = 269; 83%) NICUs compared with level-II NICUs ( n  = 51; 42%; p  < 0.001). Having a dedicated therapy team was related to having more NICU beds ( p  < 0.001), being part of a free-standing children's hospital or children's hospital within a hospital ( p  < 0.001), and being part of an academic medical center or community hospital ( p  < 0.001). Having a dedicated therapy team was more common in the Southeast, Midwest, Southwest, and West ( p  = 0.001) but was not related to the proportion of the community living in poverty or belonging to racial/ethnic minorities ( p  > 0.05). There was an average of 17 beds per neonatal therapy FTE, a good marker of therapy coverage based on NICU size. Three-hundred U.S. based NICUs (22%) had at least one Certified Neonatal Therapist (CNT) in early 2020, with CNT presence being more likely in higher acuity NICUs (59% of level-IV NICUs had at least one CNT)., Conclusion: Understanding the composition of neonatal therapy teams at different hospitals across the U.S. can drive change to expand neonatal therapy services aimed at optimizing outcomes of high-risk infants and families., Key Points: · We estimated that there are 4,232 neonatal therapists working in NICUs in the United States.. · Dedicated therapy teams for the NICU are more common in large, high acuity NICUs.. · An average of 17 beds per neonatal therapy FTE was observed.. · In 2020, 22% of NICUs had CNTs, and CNTs were more common in large and high acuity NICUs.. · Benchmarking neonatal therapy staffing can aid in expanding NICU therapy services where needed.., Competing Interests: Several authors are board members for the Neonatal Therapy Certification Board which aims to advance skilled neonatal therapy presence to optimize NICU care. The board members/authors receive no financial gain from neonatal therapy certification., (Thieme. All rights reserved.)

Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity. Here, we describe preclinical studies and process development of clinical-scale manufacturing of trem-cel. Preclinical data showed proof-of-concept with loss of CD33 surface protein and no impact on myeloid cell differentiation or function. At clinical scale, trem-cel could be manufactured reproducibly, routinely achieving >70% CD33 editing with no effect on cell viability, differentiation, and function. Trem-cel pharmacology studies using mouse xenograft models showed long-term engraftment, multilineage differentiation, and persistence of gene editing. Toxicology assessment revealed no adverse findings, and no significant or reproducible off-target editing events. Importantly, CD33-knockout myeloid cells were resistant to the CD33-targeted agent gemtuzumab ozogamicin in vitro and in viv o. These studies supported the initiation of the first-in-human, multicenter clinical trial evaluating the safety and efficacy of trem-cel in patients with AML (NCT04849910)., Competing Interests: J.R.L., M.I.L., H.G.G., A.H., S.W., M.B.J., J.E., G.A., J.X.F., J.L., K.S., Y.K., H.M., J.S., J.H., and T.C. are salaried employees of Vor Biopharma Inc. and hold equity interests in the company. J.R.L., M.L., M.B.J., J.E., J.L., J.S., and T.C. are inventors on patent applications assigned to Vor Biopharma Inc. S.M. is a coinventor on patent applications related to this work, which were filed by Columbia University and are licensed to Vor Biopharma Inc. S.M. has equity ownership and is on the Scientific Advisory Board of Vor Biopharma Inc., (© 2023 VOR BIOPHARMA INC.)

Mind-mindedness is associated with positive developmental outcomes. However, much of the literature uses mostly White, middle to high socioeconomic status (SES) samples despite evidence that the benefits of mind-mindedness may vary based on degree of social risk. Additionally, few studies have examined relations between mind-mindedness and language development. The current study investigates whether mind-mindedness predicts children's language development and behavioral functioning and if family history of childhood maltreatment moderates the relation of mind-mindedness to these outcomes. Participants were 98 mothers (49.0% Black, 24.5% White, 13.3% Latina, 7.2% multiracial; 81.6% low SES per Hollingshead classifications) and their children (49 boys, 49 girls) from the Rochester, New York area recruited at Time 1 ( M age = 13.34 months) and followed up twice ( M ages = 27.51 [Time 2] and 39.31 months [Time 3]). Mother-child dyads participated in videotaped free play interactions at Times 1 and 2. Using transcripts of these interactions, we coded mind-mindedness at Times 1 and 2 and children's internal state language at Time 2. Mothers reported on children's behavioral functioning at Time 3. Findings revealed that Time 2 mind-mindedness predicted fewer Time 3 behavioral difficulties in children from maltreating families but did not predict behavioral difficulties in children from nonmaltreating families. Additionally, Time 1 mind-mindedness predicted children's Time 2 use of decontextualized internal state language. Findings highlight the importance of examining mind-mindedness in higher risk populations and how mind-mindedness can be leveraged as a protective factor to prevent future maladjustment in children at risk for adverse outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Mothers play an important role in providing positive sensory experiences to their infants during NICU hospitalization. However, little is known regarding maternal perceptions about sensory-based interventions in the NICU. Further, understanding maternal perceptions was an important part of the process during development of the Supporting and Enhancing NICU Sensory Experiences (SENSE) program., Methods: Twenty mothers of very preterm infants were interviewed after NICU discharge and asked open-ended questions about sensory-based interventions they performed in the NICU and probed about their perceptions related to the development of a sensory-based guideline and the use of volunteers to provide sensory-based interventions when unable to be present in the NICU. Interviews were transcribed and uploaded into NVivoV.12 for content analysis., Results: Mothers reported that kangaroo care was a common sensory intervention they performed in the NICU. Of the 18 mothers who commented on the development of a sensory-based guideline, 17 (94%) said they would be accepting of one. Among 19 mothers, 18 (95%) supported volunteers conducting sensory-based interventions in their absence. Identified themes included: 1) Perceptions about development of a sensory-based guideline, 2) Perceptions of interactions with healthcare providers, 3) Maternal participation in sensory interventions, 4) Maternal experience, and 5) Emotions from mothers., Conclusion: Maternal perceptions regarding the development of a sensory-based guideline were favorable, and the SENSE program has since been finalized after incorporating important insights learned from stakeholders in this study. Mothers' perceptions were tied to their NICU experiences, which elicited strong emotions. These findings highlight important considerations when developing family-centered interventions., Competing Interests: RP and JS are authors of the SENSE Program. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lisle, Buma, Smith, Richter, Satpute and Pineda.)

Introduction: Healthcare organisations have had to make adaptations to reduce the impact of the Coronavirus 2019 (COVID-19) pandemic. This has necessitated urgent reconfiguration within inflammatory bowel disease (IBD) services to ensure safety of patients and staff and seamless continuity of care provision., Aim: To describe the adaptations made by a large inflammatory bowel disease service, caring for over 3,500 IBD patients, in response to the COVID-19 pandemic., Methods: A diary record of responses to the pandemic were logged, and meeting minutes were reviewed. Data were recorded from IBD advice lines, multidisciplinary team (MDT) meeting minutes, infusion unit attendances, and electronic referral systems for the 8-week period from 9 March 2020 until 2 May 2020. Descriptive analysis was performed., Results: The IBD service at Hull University Teaching Hospitals NHS Trust (IBD Hull) instituted rapid structural and functional changes to the service. Outpatient services were suspended and substituted by virtual consultations, and inpatient services were reduced and moved to ambulatory care where possible. The delivery of biologic and immunomodulatory therapies was significantly modified to ensure patient and staff safety. There was a substantial increase in IBD advice line calls., Conclusion: The rapidly evolving COVID-19 pandemic required a prompt response, regular reassessment and planning, and continues to do so. We share our experience in of the successful adaptations made to our IBD service., (© Royal College of Physicians 2020. All rights reserved.)

The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression. Alterations in cell-surface glycosylation associated with oncogenesis enhances AML blast binding to E-selectin and enable promotion of pro-survival signaling through AKT/NF-κB pathways. In vivo AML blasts with highest E-selectin binding potential are 12-fold more likely to survive chemotherapy and main contributors to disease relapse. Absence (in Sele -/- hosts) or therapeutic blockade of E-selectin using small molecule mimetic GMI-1271/Uproleselan effectively inhibits this niche-mediated pro-survival signaling, dampens AML blast regeneration, and strongly synergizes with chemotherapy, doubling the duration of mouse survival over chemotherapy alone, whilst protecting endogenous HSC.

Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy., Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted. The survey evaluated provider characteristics and general practice in the setting of ASUC, followed by a vignette with linked questions., Results: The response rate of the survey was 31% (209/682 IBD section members). 134 (78%) reported they would use standard infliximab dose (5 mg/kg) while 37 (22%) favoured a higher front-loading dose of 10 mg/kg citing low albumin, high C-reactive protein as their reason for their preference. IBD specialists chose the higher front-loading dose more often compared with other gastroenterologists (p=0.01) In the specific case vignette, accelerated induction (AI) was favoured by 51% of the respondents while 25% used the standard induction regime and 19% favoured colectomy. IBD specialists more often favoured AI compared with other gastroenterologists (p=0.03) with the main reason being presence of predictors of low infliximab levels (74%). The reasons cited for favouring standard induction (n=57) included lack of evidence for AI (18), their usual practice (11), unlicensed regime (7), and safety concerns (4)., Conclusions: There are significant variations in practice in the use of infliximab rescue therapies with an urgent need for development of care pathways to standardise practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Study Design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic edema (CO) and its impact on health services. Overall 7436 with CO were recruited in the main UK study from a range of health settings. Methods and Results: Factors relating to subjective control of arm and leg CO were defined in the UK. A total of 1565 patients were included in the study with exclusions for: no limb swelling or not recorded (1669), having concurrent arm/leg CO (272), control of assessment missing (5) and professional being unsure of control status of CO (325). Arm swelling occurred in 953 (18.5%) with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.2%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were : obesity, neurological disease and cellulitis in the last year and for leg CO, obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialized centers is complex due to sociodemographic and clinical comorbidities.

Background: There is no standardized international model for specialist lymphedema services, which covers the types of lymphedema treated and the treatments provided. The aim of this study was to provide a profile of patients attending specialist lymphedema services in different countries to explore similarities and differences. Methods and Results: The LIMPRINT core tool was used in specialist lymphedema services in the United Kingdom, France, Italy, and Turkey. Services in Turkey saw a slightly younger age group, with a higher proportion of female patients reflecting a particular focus on breast cancer-related lymphedema. There were higher levels of obesity and restricted mobility in patients in the United Kingdom compared with other countries. Italy and France saw the highest percentage of patients with primary lymphedema. Diabetes was a common comorbidity in the United Kingdom and Turkey. The United Kingdom saw the largest number of patients with lower limb lymphedema. Conclusions: The results show a wide range of complexity of patients treated in specialist lymphedema services. Some of the differences between countries may reflect different stages in the evolution of specialist lymphedema services, rather than a true difference in prevalence, with those with "younger" services treating a high proportion of patients with cancer and those with more established services treating a wider range of different types of lymphedema, including more elderly people with multiple comorbidities.

Following a release of Bacillus anthracis spores into the environment, there is a potential for lasting environmental contamination in soils. There is a need for detection protocols for B. anthracis in environmental matrices. However, identification of B. anthracis within a soil is a difficult task. Processing soil samples helps to remove debris, chemical components, and biological impurities that can interfere with microbiological detection. This study aimed to optimize a previously used indirect processing protocol, which included a series of washing and centrifugation steps. Optimization of the protocol included: identifying an ideal extraction diluent, variation in the number of wash steps, variation in the initial centrifugation speed, sonication and shaking mechanisms. The optimized protocol was demonstrated at two laboratories in order to evaluate the recovery of spores from loamy and sandy soils. The new protocol demonstrated an improved limit of detection for loamy and sandy soils over the non-optimized protocol with an approximate matrix limit of detection at 14spores/g of soil. There were no significant differences overall between the two laboratories for either soil type, suggesting that the processing protocol will be robust enough to use at multiple laboratories while achieving comparable recoveries., (Copyright © 2016. Published by Elsevier B.V.)

We present tight-binding models of 3D topological superconductors in class DIII that support a variety of winding numbers. We show that gapless Majorana surface states emerge at their boundary in agreement with the bulk-boundary correspondence. At the presence of a Zeeman field, the surface states become gapped and the boundary behaves as a 2D superconductor in class D. Importantly, the 2D and 3D winding numbers are in agreement, signifying that the topological phase of the boundary is induced by the phase of the 3D bulk. Hence, the boundary of a 3D topological superconductor in class DIII can be used for the robust realization of localized Majorana zero modes.

The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously; an important issue when these peptidases and substrates are targeted in disease.

Ovarian yolk sac tumors are highly malignant germ cell tumors that commonly occur in young women. The hepatoid yolk sac tumor is a variant form of yolk sac tumor in which there has been extensive tumor differentiation to early liver tissue. Hepatoid differentiation is traditionally considered to signify a poor prognosis. This review focuses on diagnostic criteria and establishes the optimal treatment for patients with hepatoid yolk sac tumor. Immunohistochemical stains are useful for distinguishing hepatoid yolk sac tumor from the other hepatoid-appearing tumors. With a multidisciplinary treatment approach using platinum-based regimens, the outcome is similar to those of any yolk sac tumor., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate ambulatory activity differences between youth with limb salvage procedures and typically developing youth (TDY) and assess differences in self-reported activity levels in the 2 groups, to provide a basis for physical activity assessment in patients who had undergone limb salvage surgery and treatment planning that incorporates regaining normal physical and daily living activities., Study Design: In this cohort comparison study, we compared ambulatory and self-reported activity levels in 20 youth (aged 11.7-20.8 years) who had undergone limb salvage surgery and a sex- and age-matched comparison cohort of 20 TDY. StepWatch activity monitor and Activity Scale for Kids data were used to answer these questions., Results: Significant differences were found between the youth who had undergone limb salvage surgery and the TDY in total time active each day (43% vs 48%; P = .03), median total strides per day (4487 vs 7671; P = .001), and amount of time per day at high activity levels (20 minutes vs 47 minutes; P = .001). Self-reported overall physical activity, locomotion, and standing Activity Scale for Kids subscale scores were significantly lower in the youth undergoing limb salvage surgery compared with the TDY (summary score, 88.3 vs 97.7; P = .001)., Conclusion: Patients undergoing limb salvage surgery exhibit reduced physical activity compared with normal age-matched controls., (Copyright © 2012 Mosby, Inc. All rights reserved.)

The aim of this study was to describe walking (stride) activity frequency and intensity in 428 children ages 2-15 years with a single accelerometer-based device. With comparison with published pedometer-determined data, the influence of leg length was examined. Decline in stride frequency and intensity throughout childhood increased with adjustment for leg length. The accelerometer-based device documented higher stride counts than published pedometer-based data with the greatest discrepancy in 4-5 year olds. Recommended walking levels for optimal weight throughout childhood should be examined with knowledge of the device measurement differences and the natural history of walking activity changes with age.

Bacteriophages are found wherever microbial life is present and play a significant role in aquatic ecosystems. They mediate microbial abundance, production, respiration, diversity, genetic transfer, nutrient cycling and particle size distribution. Most studies of bacteriophage ecology have been undertaken at temperate latitudes. Data on bacteriophages in polar inland waters are scant but the indications are that they play an active and dynamic role in these microbially dominated polar ecosystems. This review summarises what is presently known about polar inland bacteriophages, ranging from subglacial Antarctic lakes to glacial ecosystems in the Arctic. The review examines interactions between bacteriophages and their hosts and the abiotic and biotic variables that influence these interactions in polar inland waters. In addition, we consider the proportion of the bacteria in Arctic and Antarctic lake and glacial waters that are lysogenic and visibly infected with viruses. We assess the relevance of bacteriophages in the microbial loop in the extreme environments of Antarctic and Arctic inland waters with an emphasis on carbon cycling.

The Dundee Ready Education Environment Measure (DREEM) was administered to 70 final-year medical students and 36 first-year medical interns (pre-registration house officers). The overall total mean DREEM scores for the five subscales-namely, students' perceptions of the atmosphere, students' perceptions of learning, students' social self-perceptions, students'perceptions of teachers and students' academic self-perceptions-was 109.9 and the total mean scores for the subgroups-male students, male interns, female students and female interns-were 103.39, 111.82, 111.33 and 113.15, respectively. The lowest scores were assigned to students' social self-perceptions and students' perceptions of the atmosphere. All of the participants except the male interns recorded the highest scores for the subscale academic self-perceptions.