bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Pump Trainings for the t:slim X2 Insulin Pump With Control-IQ Advanced Hybrid Closed-Loop Technology: Real World Patient Experience
Authors: Singh Harsimran , Manning Michelle , McElwee-Malloy Molly , Habif Steph
Published: May 2021

The COVID-19 pandemic led to a digital evolution in the healthcare industry by necessitating widespread adoption of telehealth and other remote services to enable engagement with patients. Diabetes management is well suited for telehealth utilization if patients employ technology that efficiently generates, captures, and shares data with providers. Traditionally, training for automated insulin delivery devices is provided in-person to allow for a thorough understanding of the device and its use. However, during COVID-related quarantine regulations, most of these trainings needed to be conducted virtually. We performed a retrospective analysis of patient reported outcomes in people with diabetes who completed their training for the t:slim X2 pump with Control-IQ technology between April and September, 2020 and had uploaded 30 days of pump usage data to Tandem’s t:connect® web application. Most participants were adults (90%), female (54%), and had type 1 diabetes (89.9%). Mean age of the sample was 46 years (SD=18.7). Of all 1,686 participants, 1,256 had received virtual pump training while the remaining were trained in-person (n=430). Most participants reported completing their training in 1 to 2 hours (61.5%). After concluding training, participants completed an online questionnaire evaluating their training experience (8 items). Item response options included a 5-point Likert scale with higher values reflecting greater satisfaction and better experience with training. Multivariate analysis of variance indicated a significant effect of training method (virtual vs. in-person) on training-related experience (p=.020). Specifically, participants receiving virtual pump training reported greater overall satisfaction with their training (4.78 vs. 4.65, p=.012) and with the time when their training was conducted (convenient scheduling) (4.74 vs. 4.56, p=.008) compared to their counterparts who underwent in-person training. There were no significant differences between virtually trained and in-person participants on pace of training (4.71 vs. 4.57), trainer’s pump knowledge (4.82 vs. 4.74), trainer’s ability to answer their questions (4.77 vs. 4.70), and participants’ confidence to use the pump after training (4.62 vs. 4.53). In conclusion, all participants irrespective of their training method (virtual or in-person) reported a positive experience with their training for using the t:slim X2 pump with Control-IQ technology. Participants’ high scores on items evaluating their training method also reflects that their expectations of their training session were either met or exceeded. State-of-the-art technologies supporting diabetes management may benefit from patient-centric training methods to enable widespread optimal use. For future studies, it will be interesting to evaluate adherence to therapy by training method and relationship with glycemic outcomes.
Accuracy of a Point-of Care Hemoglobin A1c Assay - A Community Outreach Project
Authors: Semreen Noura , Otuonye Gene , Pena Angelica Medina , Rastogi Natasha
Published: May 2021

Glycated hemoglobin (HbA1c) is an invaluable tool in diabetes mellitus (DM) management. Conventionally obtained via venous blood sampling, point-of-care (POCT) capillary HbA1c measurement offers an opportunity for immediate treatment modification, reduced cost & increased patient satisfaction. While previous studies using the POCT HbA1c test A1cNow+ have shown accuracy within a 0.5% range from the gold standard venous HbA1c, we noted discrepancy in our community health clinic & sought to evaluate the accuracy of POCT HbA1c levels compared to venous HbA1c levels to guide our clinical decision-making.

In this 2-part study, we compared POCT HbA1c levels measured via a single use A1CNow+ HbA1c monitoring device & venous HbA1c samples measured by a standardized lab. Part1: after retrospective chart review, we identified 262 patients with prediabetes, Type1 or Type2 DM based on ADA guidelines who attended our clinic from January 2019-June 2019 & received POCT HbA1c with A1cNow+ testing during their visit. Of those cases, 47 patients also had a venous HbA1c at a standardized laboratory within 1 month of having their POCT HbA1c performed in our clinic. Part2: We noted variability in the temperature storage of A1CNow+ test strips. Storage was standardized to room temperature as per device instructions in June 2019. We subsequently reviewed charts from June 2019-December 2019 & identified 118 patients who had both POCT HbA1c & venous HbA1c measurement within a 1 month period.

Patients was categorized into subgroups per ACP guidelines for DM control: prediabetic (HbA1c 5.7–6.4%), controlled DM (HbA1c 6.5 to 8.0%) & uncontrolled DM (HbA1c >8.0%). The average difference between POCT & venous HbA1c tests was calculated & analyzed for statistical significance using paired t test analysis. Part1: For patients in prediabetic, controlled & uncontrolled DM subgroups, the mean difference between A1cNow+ & standardized venous HbA1c testing was 0.68% (p= 0.004), 1.15% (p= <0.0001) and 1.36% (p= 0.0003) respectively. Part2: After standardization of test strip storage, the mean difference between A1cNow+ & venous HbA1c testing for prediabetic, controlled & uncontrolled DM patients was 0.33% (p= 0.002), 0.41% (p= 0.011) and 1.26% (p= <0.0001) respectively.

POCT HbA1c provides a unique opportunity to immediately address glycemic control. Its advantages are especially apparent in a patient population with limited resources & poor follow up, as in our clinic. Although standardizing test storage improved overall concordance between A1cNow+ HbA1c testing & venous HbA1c, there was still a statistically significant larger mean difference in uncontrolled DM patients. In prediabetic & controlled DM patients, however, POCT HbA1c was accurate within previously published reports of a 0.5% range when compared to venous HbA1c. An algorithm has since been developed to guide our clinical decision making with these findings.
Effects of Evogliptin as Add on in Type 2 Diabetes (T2DM) Subjects Inadequately Controlled With Metformin and Glimepiride Combination
Authors: Guha Shaibal
Published: May 2021

Objective: To achieve targeted glycemic control people with diabetes required multiple drug therapy. We retrospectively studied effect of adding newly approved DPP4i evogliptin in T2DM subjects having high HbA1c value despite being on tolerable stable doses of Metformin and Glimepiride. Methods: We retrospectively analysed the effects of evogliptin 5 mg OD over 6 month preriod when added to patients who were initially having HbA1c ≥ 7.5% on on stable fixed dose combination of Metformin (1000 -2000 mg/day) and glimiperide (2 - 4 mg/day) at least from 3 months prior. Any patients who were other OHA drugs or in Insulin of have been up or down titrated of the studied drug were excluded. We compared HbA1c, fasting (FPG), postprandrial (PPG) plasma glucose, total cholesterol (TC), triglyceride (TG), HDL, LDL at baseline and after 6months of evogliptin initiation. Self-monitored blood glucose (SMBG) was performed using the patients’ own BG meter. Physicians gave all patients training to ensure they could perform SMBG correctly and accurately. Results: Data of 185 subjects [85(46%) females, Mean age 52.3±2.8 years, mean duration of diabetes 8.2±1.9], who met the inclusion criteria were extracted for analysis from the hospital and clinics records. A drop in HbA1c from 8.8±1.1 to 7.8±0.5% (p<0.05) were resulted after addition of evogliptin. FPG decreased from 159.2±13.5 to 128.3±11.2 and PPG from 238.2±28.7 to 188.1±22.6 respectively (p <0.05). Total cholesterol (TC), triglyceride (TG) were significantly improved after addition of evogliptin, whereas little effect on LDL and HDL. There was no incidence of severe hypoglycemia, though 7 (3.8%) cases of suspected hypoglycemia were managed at home. Conclusion: Evogliptin is a suitable add-on option for those with high HbA1c values as it offer low risk of hypoglycemia despite significant improvement in glycemic parameters.
Incidence and Factors Associated With Genitourinary Infections Among Type 2 Diabetes Mellitus Patients on SGLT2 Inhibitors: A Single-Center Retrospective Cohort Study
Authors: Caro Marilyn Katrina C , Cunanan Elaine Cheeay , Kho Sjoberg Ang
Published: May 2021

Background: The efficacy of SGLT2 inhibitors for diabetes is consistent across several studies; however, the risk of genitourinary infection due to these drugs has also been cited.

Objective: To determine the incidence and factors associated with genitourinary infection among type 2 diabetes mellitus patients on SGLT2 inhibitor seen at the University of Santo Tomas Hospital

Methodology: The study utilized a retrospective cohort design. Participants included 253 Type 2 diabetes mellitus patients who started SGLT2 inhibitor treatment from January 1, 2014 to June 30, 2019. Data collection via medical charts review was performed from April 1 to October 1, 2020. Multiple logistic regression analysis was performed to determine the factors associated with genitourinary infection. Stata MP version 14 software was used for data analysis.

Results: The 3-month and 6-month incidence of genitourinary infection among patients treated with SGLT2 inhibitors are 2.37% and 21.78%, respectively. A significant difference in the probability of genitourinary infection across the three drugs was observed (p=0.0019). Pairwise analysis showed lower probability of infection among patients treated with canagliflozin compared to empagliflozin and dapagliflozin. Factors associated with genitourinary infection include high HbA1c at the time of treatment initiation and SUR and insulin use. The same set of factors were recorded for males. Among females, only HbA1c and eGFR at the time of SGLT2 inhibitor initiation were significantly associated with genitourinary infection.

Conclusion: The study results revealed that genitourinary infection is common among patients taking SGLT2 inhibitors, especially dapagliflozin and empagliflozin. Several factors were associated with urinary and genital infection, and risk factors vary by sex. These factors include high BMI, high HbA1c levels at the time of treatment initiation, longer duration of diabetes, low eGFR, and concomitant use of insulin and/or SUR.
Role of Bariatric Surgery in Managing Metabolic Syndrome
Authors: Iqbal Iqra , Khan Muhammad Atique Alam , Tariq Shafaq , Slusser Jonathan
Published: May 2021

Background: Lifestyle modifications provide a limited control of diabetes mellitus type 2 (DM2), especially in patients with morbid obesity and uncontrolled DM. Compared with non-surgical treatment, bariatric surgery achieved more sustained weight loss and higher remission rates of DM2. Roux-en-Y gastric bypass (RYGB) has been the most common procedure in the past but sleeve gastrectomy (SG) with duodenal switch (DS) is gaining more popularity now. Objective: To compare the significant differences in the outcomes of these procedures; such as the reduction in hemoglobin A1c (HbA1c), weight, basic metabolic index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk score of the patients at our community hospital.

Methods: This was a retrospective observational study consisting of a chart review of 151 patients during 2016 to 2019. Patients included were >18 years old, and underwent one of the three types of bariatric surgeries, including RYGB, SG and sleeve with DS. Comparison between different continuous variables was made using analysis of variance. Chi square analysis was used to determine associations between different outcomes and various categorical variables.

Results: Among all, 33.1% had SG, 33.8% had RYGB and 33.1% had DS. The median age was 66 years and 71.5% were females. Median height was 63 inches. 84.8% were white, 14.6% were African American and 0.7% were Asian. The associated comorbidities were asthma, hypertension, dyslipidemia, DM, smoking and coronary artery disease. Median weight prior to surgery was 280 pounds (lb) and reduced to a median weight of 240 lb. Median BMI before surgery was 44 kg/m2 and reduced to 39 kg/m2. Median blood pressure (BP) was 128/74 mmHg and reduced to 120/68 mmHg. Patients with elevated BP reduced from 70% to 20% in SG, 66.7% to 49% in RYGB and 82% to 54% in DS. Fasting blood sugar reduced from a median of 98 mg/dl to 87 mg/dl. HbA1c reduced from a median of 6 to 5.4. ASCVD risk score reduced from 4 to 2. Mean difference in HbA1c reduction was 0.81 for SG, 1.44 for RYGB and 2.19 for DS. Prior to surgery, 43% patients had DM, 16.6% had prediabetes and 40.4% were nondiabetic. Three months later, patients with DM2 reduced to 14.8% and prediabetes reduced to 10.7%. Patients with DM in SG group reduced from 14% to 12.2% and prediabetics reduced from 12 to 6%. In RYGB group, DM reduced from 56.9% to 16% and prediabetics increased from 13.7% to 24%. In DS group, DM reduced from 58% to 16% and prediabetics reduced from 24% to 2%. Insulin users reduced from 4% to 2 % in SG, 21.6% to 3.9% in RYGB and 22% to 6% in DS. Median number of DM2 medications reduced from 1 to 0. Conclusion: Our study demonstrates the differences in the reduction of HbA1c, weight, BMI and ASCVD risk score among various bariatric surgery procedures. It suggests that DS leads to a greater reduction in the HbA1c and ASCVD risk scores as compared to RYGB, although the risks of malabsorption complications are considerable.
The Use of Cultural Competency in Decreasing Diabetes Outcomes Disparities in a Community Health Care Setting
Authors: Toth David W , Vittini Radairy M
Published: May 2021

In the United States, the prevalence of diabetes in the Latnix population is roughly 70% higher than in non-Latinx whites. Along with this, many studies have shown that the rate of complications, both macro- and microvascular, in this population is also disproportionately higher. Given that complication rates mirror glycemic control, as evidenced by studies such as the DCCT and UKPDS, the increased rate of poor glycemic control is likely one of the most important factors contributing to this. Most efforts at controlling diabetes in a population have aimed at a heterogeneous cohort in terms of race and ethnicity, yet poor control disproportionately affects the Latinx groups. North Shore Community Health Center is a Federally Qualified Health Center located around the communities of Salem, Peabody, and Gloucester, MA. These areas are ethnically diverse, and the vast majority of the Latinx population are Dominican. In fact, roughly 50% of the clinic population is Latinx. After prioritizing glycemic control as a goal for 2019, we utilized a population health strategy to identify patients with A1c >9% (poor control as defined by UDS measurements). These patients were given an appointment with the only endocrinologist in the clinic, who, through a Dominican Spanish translator and using joint decision making, decided on appropriate medication. They were then followed at least weekly at first by a nurse who also was Dominican and lived in the community. She counseled patients on culturally-appropriate diet recommendations, activity, screening, monitoring, and provided access to other specialties (e.g. podiatry, ophthalmology) as needed. The rate of A1c >9% in the clinic had been 35–40% prior 2019. At the end of 2019, the rate was 27%, with a disproportionaltly lower rate in the Latinx population (23%). Our conclusion is that a culturally sensitive diabetes program will eliminate these health disparities
Type 2 Diabetes Management in Older Adults: A Personalized Approach
Authors: Miles Cristy , Ali Rabia , Nathan Aviva , Cui Michael , Zhu Mengqi , Pusinelli Mariko , Press Valerie , Huang Elbert
Published: May 2021

Aging is considered a significant risk factor for diabetes, and over the next decade, the largest increase in diabetes prevalence is expected to be in older adults. Our study aimed to investigate the challenges in managing type 2 diabetes in older adults and its multifactorial components that affect diabetes goal setting. “My Diabetes GOAL” hypothesized that a nursing intervention, along with a collaborative approach to management, education, and care, can engage older patients in personalized goal setting and address barriers to quality of life. A total of 88 patients with type 2 diabetes mellitus were included in this 6-month randomized controlled trial, with 42 patients enrolled in the intervention arm and 46 patients in the delayed-start control arm. Patients were required to complete a survey delivered through the patient portal to initiate personalized goal setting and care management support. Patients in the intervention arm received their first telephonic care management call by a study team nurse within five business days of the initial survey completion. The nurse discussed survey responses, barriers, and concerns the patient may have involving their care. Barriers included hypoglycemia, medication, co-morbidity, and physical activity. For this abstract, we report the frequency of care management topics for all 88 patients. The majority of our patient population identified as African American (68%) and female (68%). The average A1c at baseline was 7 %. For every monthly call, A1c goal setting and education was a required discussion topic and did not vary significantly throughout the intervention (73% month one, 74% month six). During the first call, hypoglycemia was addressed among 56% of participants, and education on medication was provided to 64%. Co-morbidities (heart failure, incontinence, depression, chronic pain, falls, lung conditions, malignancies) were highly prevalent, with 68% having one or more. Physical activity was discussed in 42% of conversations with participants, and a referral (diabetes education, physical therapy) was needed by 25%. After six months, discussions regarding hypoglycemia (14%), medication (19%), co-morbidities (56%), physical activity (22%), and referrals (6%) were reduced. These results suggest that personalized telephonic care management for older adults can positively impact patient outcomes. Diabetes care management is not a one size fits all. Personalized goal setting was successfully discussed based on an individual’s risk factor, which took into consideration co-morbidities and physical mobility barriers. Future studies should evaluate long-term clinical outcomes with a randomized control design.
A Novel Peptide Antagonist of the Human Growth Hormone Receptor
Authors: Basu Reetobrata None , Kopchick John Joseph
Published: May 2021

The human growth hormone (GH) secreted by the anterior pituitary, binds to its cognate growth hormone receptor (GHR) and regulates longitudinal growth, organ development, metabolism of carbohydrate, protein, and lipid, as well as disease states like diabetes and cancer. GH action has also found to be a critical determinant of human lifespan. Consequently, there is considerable interest around developing an inhibitor of the GH action. The first and only antagonist of the GHR - pegvisomant - was developed at our lab more than 20 years back and is currently an FDA approved prescription drug for treating acromegaly, a condition of GH excess. Here we present the design, development, and initial characterization of a novel peptide antagonist of the human GHR. The novel antagonist termed ‘S1H’ is a 16-amino-acid peptide designed as a direct sequence mimetic of a unique fragment of the site-1 binding helix of the human GH molecule. To this end we have characterized S1H with mass spectrometry, circular dichroism spectropolarimetry, and in vitro biological assays using human cell lines expressing GHR. S1H inhibited GH induced STAT5 phosphorylation, a hallmark of GH induced intracellular signaling, in a dose-dependent manner in multiple cell lines. Furthermore, using alanine scanning mutagenesis studies, we identified a strong correlation between the helical propensity and biological activity of S1H. Taken together, our results confirm that S1H is a novel GHR inhibitor with prospective applications in human disease conditions on one hand, and also is a valuable molecular tool to study the nature of human GH-GHR interactions. We currently continue to characterize S1H for binding kinetics and in vivo effects on suppressing GH action.
Cells to Systems Screening for Thyroid Hormone Disrupting Chemicals in the Brain
Authors: Furlow J David , Mengeling Brenda J
Published: May 2021

Precisely timed and regulated thyroid hormone (TH) levels are essential for vertebrate development and metabolism. To detect environmental chemicals that disrupt TH action, we developed an integrated luciferase reporter cell line in rat pituitary GH3 cells that is TH responsive through activation of endogenous thyroid hormone receptors (TRs). High throughput screening as part of the Tox21 program identified several non-TH related positive hits as RXR agonists, a supposed “silent” heterodimer partner for TRs. These data showed RXR agonists can affect TR signaling at least in pituitary cells. We extended these results to our sensitive and specific in vivo model for TH action, Xenopus laevis metamorphosis. We previously demonstrated that RXR agonists like organotins and the pharmaceutical bexarotene, strongly potentiate (and RXR antagonists inhibit) TH induced metamorphic programs, at the morphological, cellular (e.g. apoptosis or proliferation), transgenic reporter gene levels, and transcriptomic responses in tadpole tails. We have now extended this analysis to include RNA-Seq experiments over distinct time points in the tadpole brain, a common target of TH in humans and frogs, revealing specific gene sets particularly affected by TH and RXR ligands working in concert. Very few genes were affected by RXR ligands alone. The remarkable overlap between the environmental toxicant tributyltin and the synthetic and specific RXR ligand bexarotene regulated transcriptomes provides strong evidence that they have a common molecular target in multiple tissues. We have also created germline mutations in all RXR family members in Xenopus tropicalis (alpha, beta and gamma), and both copies of the duplicated TR beta gene in Xenopus laevis via genome editing approaches. This will allow us to further investigate TR-RXR heterodimer function across tissues and developmental timeframes, and in response to known and suspected TR and RXR ligands. Our studies revealed an unanticipated degree of TR and RXR ligand interactions in vitro and in vivo, highlighting a surprising role of RXRs as avenues for TH endocrine disruption, including the brain.
Expression Patterns of Analgesic Metabolising Machinery in 1st and 2nd Trimester Human Fetal Liver and Gonads
Authors: Zafeiri Aikaterini , Fowler Paul A
Published: May 2021

Use of over-the-counter analgesics during pregnancy is widespread globally. Most analgesic compounds can freely diffuse through the placental feto-maternal interface and reach the developing fetus. Current literature suggests an endocrine disruptor (ED) potential of in utero exposure to these compounds. The liver is the primary site of contact with EDs in the fetus. Exposure of the fetal gonads can also alter reproductive function with potential intergenerational effects. We aimed to characterise the metabolic capability of these fetal organs. RNA sequencing was performed in 80 second trimester human fetal livers and 48 fetal gonads (balanced for fetal age and fetal sex). Samples were collected from elective terminations of normal pregnancies (liver 11-19 weeks, FeGo study: REC 04/S0802/21, and gonads 6-17 weeks, as previously described1. RNA was extracted and Illumina NextSeq was used to produce 76 bp single end (liver) or paired end 2x50 bp (gonads) sequencing reads. Reads were quality controlled, aligned to the human reference genome and quantified at gene regions. Statistical analyses involved an ANOVA model of two-way interactions between fetal sex and fetal age. All organs expressed phase I and II metabolising enzymes and drug transporters involved in the pharmacokinetic and pharmacodynamic pathways of over-the-counter analgesics. The human fetal liver expressed ABCC2, ABCC3, ABCC4 and ABCG2 receptors at similar levels between males and females. Expression of cytochrome p450 enzymes CYP2A6, CYP2C8, CYP2C9, CYP2E1, CYP3A4 involved in metabolism of the analgesics paracetamol and ibuprofen, all increased with gestational age in the liver. Expression of GSTM1, GSTP1, GSTT1, SULT1A1, SULT1A3, SULT1A4, SULT1E1, SULT2A1, UGT2B4, UGT2B7 and UGT2B15 metabolising enzymes also increased during gestation, while fetal hepatic GSTP1 expression showed a significant 2-way interaction between both sex and age. Fetal gonads expressed ABCC4 and ABCG2 transporters, with transcript levels demonstrating significant sex-specific and gestational age differences. Fewer analgesic metabolising enzymes were expressed in the gonads than the fetal liver, including CYP2E1, GSTP1 and SULT1A1, all significantly altered by gestation and fetal sex. Our results reveal expression of major analgesics metabolic and transport components within the human fetal liver, ovaries and testes between gestation weeks 7-19. Significant sex alterations in transcript levels also suggest sexually dimorphic metabolic activity of these organs during fetal life. In conclusion, analgesics can be transported into fetal liver and gonad cells and metabolised into bioactive forms, posing toxicity risks for the developing fetus.1. Lecluze E, Rolland AD, Filis P, et al. Dynamics of the transcriptional landscape during human fetal testis and ovary development. Hum Reprod. 2020;35(5):1099-1119.
Neuromechanics of Middle-Distance Running Fatigue: A Key Role of the Plantarflexors?
Authors: WILLER JASMIN , ALLEN SAM J. , BURDEN RICHARD J. , FOLLAND JONATHAN P.
Published: May 2021

Identifying the neuromechanical changes during high-intensity running to fatigue may highlight the biomechanical limitations to performance and indicate mitigation/training strategies.

Purpose

This study aimed to investigate the changes in lower limb kinematics, kinetics, and muscle activation during a high-intensity run to fatigue (HIRF).

Methods

Eighteen male and female competitive middle-distance runners performed a HIRF on an instrumented treadmill at a constant but unsustainable middle-distance speed (~3 min) based on a preceding maximum oxygen uptake (V˙O2max) test. Three-dimensional kinematics and kinetics were collected and compared between the start, 33%, 67%, and the end of the HIRF. In addition, the activation of eight lower limb muscles of each leg was measured with surface EMG (sEMG).

Results

Time to exhaustion was 181 ± 42 s. By the end of the HIRF (i.e., vs the start), ground contact time increased (+4.0%), whereas flight time (−3.2%), peak vertical ground reaction force (−6.1%), and vertical impulse (−4.1%) decreased (all P < 0.05), and joint angles at initial contact became more (dorsi)flexed (ankle, +1.9°; knee, +2.1°; hip, +3.6°; all P < 0.05). During stance, by the end of the HIRF: peak ankle plantarflexion moment decreased by 0.4 N·m·kg−1 (−9.0%), whereas peak knee extension moment increased by 0.24 N·m·kg−1 (+10.3%); similarly, positive ankle plantarflexion work decreased by 0.19 J·kg−1 (−13.9%), whereas positive knee extension work increased by 0.09 J·kg−1 (+33.3%; both P < 0.05) with no change in positive hip extension work. Hip extensor surface EMG amplitude increased during the late swing phase (+20.9–37.3%; P < 0.05).

Conclusion

Running at a constant middle-distance pace led primarily to the fatigue of the plantarflexors with a compensatory increase in positive work done at the knee. Improving the fatigue resistance of the plantarflexors might be beneficial for middle-distance running performance.
Mammograms and Mortality: How Has the Evidence Evolved?
Authors: Kowalski Amanda E.
Published: May 2021

Decades of evidence reveal a complicated relationship between mammograms and mortality. Mammograms may detect deadly cancers early, but they may also lead to the diagnosis and potentially fatal treatment of cancers that would never progress to cause symptoms. I provide a brief history of the evidence on mammograms and mortality, focusing on evidence from clinical trials, and I discuss how this evidence informs mammography guidelines. I then explore the evolution of all-cause mortality relative to breast cancer mortality within an influential clinical trial. I conclude with some responses to the evolving evidence.
The Rise of Research Teams: Benefits and Costs in Economics
Authors: Jones Benjamin F.
Published: May 2021

Economics research is increasingly performed in teams, and team-authored work has a large and increasing impact advantage. This article considers the benefits and costs of this “rise of teams.” Among its benefits, teamwork allows individuals to aggregate knowledge in productive and novel ways. For example, as knowledge accumulates over time, individuals become narrower in their expertise, and teamwork is a natural organizational approach to aggregating expertise and maintaining one’s reach. But teamwork also brings costs. For example, teamwork divides and obscures credit, which is central to the reward system of science. By clouding credit assignment, teamwork can undermine individual career progression and exacerbate issues of bias. In addressing the rise of teamwork, this paper further considers institutional innovations, especially those inspired by the hard sciences, that can help limit the costs teamwork imposes while realizing the benefits.
Direito administrativo sem tribunais
Authors: J. Walker Christopher
Published: May 2021

Como parte do Simpósio da UCLA Law Review sobre as Salvaguardas da Nossa República Constitucional, este artigo defende que é um erro fixar os tribunais como a salvaguarda central no estado administrativo moderno. Não é pequeno o número de exemplos que prescindem de tribunais no Direito Administrativo. Dito de outra forma, as agências federais regulam-nos em muitas formas significativas, e por vezes assustadoras, que ou escapam inteiramente à revisão judicial ou estão pelo menos substancialmente isoladas de tal revisão. Este artigo analisa o fenômeno. Esboça sete categorias de tais ações das agências, baseando-se em exemplos tanto da Administração Obama como da Administração Trump e destacando algumas das pesquisas relevantes. O artigo conclui com algumas observações relativas às implicações do direito administrativo sem tribunais para a teoria e doutrina do direito administrativo e um apelo a uma maior atenção acadêmica.
Part 2: COVID-19 and knowledge for midwifery practice—impact and care of the baby
Authors: Green Janet , Jones Linda , Petty Julia , Bromley Patricia , Fowler Cathrine , Walker Karen
Published: May 2021

It is well-known that newborn infants are more susceptible to infection due to their immature host defence mechanisms. However, in relation to the COVID-19 virus, it appears that the naivete of the neonatal immune system has afforded some protection against the inflammatory response experienced by adolescents and adults. That said, COVID-19 and the associated changes in practice and policies implemented in response to the pandemic, has had an impact on the care of the baby during the perinatal and neonatal period. This article is the second in a two-part series focusing on important care issues relating to the newborn baby specifically, taken from an integrative review of current literature within the maternal and neonatal field. This paper analyses the emerging themes from selected literature to add to a developing body of knowledge; namely, physiological differences between the newborn baby and adult, neonatal management including, preterm labour and delivery, newborn resuscitation, investigations, care of the newborn, the importance of human milk and breastfeeding, and the implications of COVID-19 restrictions. Finally, an overview of the World Health Organization guidance will be outlined for a global view and summary.
Decision-making in the birth space
Authors: Huschke Susann
Published: May 2021

Susann Huschke discusses how communicating with birthing people in the current technocratic maternity systems in Ireland and elsewhere can inhibit the birthing person's meaningful involvement in decision-making
Neonatal palliative care
Authors: Kerelo Sydney
Published: May 2021

This first-of-a-kind project rolls out across the UK, transforming neonatal palliative care and helping thousands of families
Genus und Sexus im Konflikt.
Authors: Hübner Julia
Published: May 2021

The specialty of hybrid nouns is their different agreement according to certain features of the agreement target. They result from a conflict within in the gender assignment system. For example, the German noun Mädchen (semi-transparent diminutive for denoting a girl) is grammatical neuter but it refers to a female person. In German, nouns denoting females are feminine but diminutives are neuter. Since both rules apply, you can refer to Mädchen with a neuter (es) but also with a feminine pronoun (sie).

There are different factors which influence the agreement pattern: the linear distance between noun and pronoun and the type of agreement target. So far there are only few studies on the influence of possible non-grammatical factors such as the age of the referent. In this paper, I elaborate on those factors and present the results of a discourse completion task focusing on the influence of a sexualized context.
Neutrales Rufnamengenus zwischen Grammatik und Pragmatik
Authors: Busley Simone , Fritzinger Julia
Published: May 2021

In numerous German dialects and in Luxembourgish, female first names can take on both feminine and neuter gender agreement, thus leading to gender variation on a paradigmatical level and gender mismatches on a syntactical level. This is contradictory to canonical conceptions of gender systems and can be interpreted as a case of degrammaticalization. Here, grammatical gender has been refunctionalized as a socio-pragmatic marker which indicates the age and status of the woman referred to as well as the speaker’s relationship to her. In some varieties, regrammaticalization of gender assignment resulted in female first names always taking neuter agreements.

The present article focusses on the reconstruction of the stages of degrammaticalization and regrammaticalization of gender assignment based on data of the research project “Das Anna und ihr Hund – Weibliche Rufnamen im Neutrum”. Analyses of the data indicate that personal pronouns as the targets most prone to differing agreement played a key role in this process.
Annali, Ruedi, Mami.
Authors: Christen Helen , Baumgartner Gerda
Published: May 2021

Data of the dialect research project “Das Anna und ihr Hund. Weibliche Rufnamen im Neutrum” indicate the important role of diminutive names in terms of the historical develop-ment and consolidation of the onymic neuter gender assignment. The focus in the present arti-cle lies therefore on the forms and the use of diminutive names (e. g. Anneli, Ruedi) in Swiss-German dialects.

Based on diachronic evidence from literary works and regional dictionaries, differences in the diminution of male and female names are historically traced and substantiated. It is for prag-matic reasons that female kinship names (e. g. Mami) are crystallized to be the last bastion for the neutral gender assignment which opens up new perspectives on the diachronic emergence of this phenomenon. The consideration of further onymic suffixes in the outlook brings up a debate on the disagreement of gender and sex which is considered to be a possible objective of the suf-fixation itself.
Detection of small targets in the infrared: an infrared search and track tutorial
Authors: Driggers Ronald , Pollak Eytan , Grimming Robert , Velazquez Ectis , Short Robert , Holst Gerald , Furxhi Orges
Published: May 2021

Airborne target detection in the infrared has been classically known as infrared search and track or IRST. From a military point of view, it can be described as target detection at long ranges where the target image is subpixel in size. Here, the target is “unresolved.” It can also describe the detection of aircraft near the observer using distributed apertures in a spherical detection field. From a commercial point of view, an important application is drone detection near live airport operations. As drones become more common, the dual-use functionality of IRST systems is expanding. Technology improvements for IRST systems include the wide proliferation of infrared staring focal planes. New readout integrated circuits allow for time-delay-integration of large format detectors. Stare-step sensors in the future appear to be as common as gimbal-scanned thermal imagers. Detection probability analysis and IRST sensor design is different than targeting system design. We provide a tutorial here on IRST system calculations as well as discussions on broadband versus spectral calculations and new technology considerations.
Demonstration of high-speed thin-film lithium-niobate-on-insulator optical modulators at the 2-µm wavelength
Authors: Pan Bingcheng , Hu Jinyao , Huang Yishu , Song Lijia , Wang Jingyi , Chen Pengxin , Yu Zejie , Liu Liu , Dai Daoxin
Published: May 2021

Optical communication wavelength is being extended from the near-infrared band of 1.31/1.55 µm to the mid-infrared band of 2 µm or beyond for satisfying the increasing demands for high-capacity long-distance data transmissions. An efficient electro-optic (EO) modulator working at 2 µm is highly desired as one of the indispensable elements for optical systems. Lithium niobate (LiNbO3) with a large second-order nonlinear coefficient is widely used in various EO modulators. Here, we experimentally demonstrate the first Mach-Zehnder EO modulator working at 2 µm based on the emerging thin-film LiNbO3 platform. The demonstrated device exhibits a voltage-length product of 3.67 V·cm and a 3-dB-bandwidth of >22 GHz which is limited by the 18 GHz response bandwidth of the photodetector available in the lab. Open eye-diagrams of the 25 Gb/s on-off keying (OOK) signals modulated by the fabricated Mach-Zehnder EO modulator is also measured experimentally with a SNR of about 14 dB.
High-contrast OPCPA front end in high-power petawatt laser facility based on the ps-OPCPA seed system
Authors: Xiao Qi , Pan Xue , Jiang Youen , Wang Jiangfeng , Du Lifeng , Guo Jiangtao , Huang Dajie , Lu Xinghua , Cui Zijian , Yang Shuaishuai , Wei Hui , Wang Xiaochao , Xiao Zhuli , Li Guoyang , Wang Xiaoqin , Ouyang Xiaoping , Fan Wei , Li Xuechun , Zhu Jianqiang
Published: May 2021

A high-energy, high-beam-quality, high-contrast picosecond optical parametric chirped-pulse amplification (ps-OPCPA) laser system was demonstrated. The pulse from a femtosecond oscillator was stretched to 4 ps, after which it was amplified from 140 pJ to 600 µJ by an 8 ps/6 mJ pump laser in two non-collinear OPCPA stages. The total gain was >106, and the root mean square of the energy stability of the laser system was 1.6% in 10 h. The contrasts of the solid and fiber mode-locked femtosecond oscillator-seeded ps-OPCPA systems were compared, and a signal-to-noise ratio of >1011 was achieved. Using this system, the contrast of the front end in high-power picosecond petawatt laser facility was improved by ∼40 dB to >1011, beyond ∼200 ps ahead of the main pulse with an output level of 60 mJ.
Compact quasi-optical mode converter based on anisotropic metasurfaces
Authors: Fu Wenjie , Hu Shijie , Zhang Chaoyang , Guan Xiaotong , Yan Yang
Published: May 2021

In this paper, a novel compact quasi-optical mode converter based on anisotropic metasurfaces for high-order mode terahertz electronic devices is presented. To demonstrate the design model, a Ka-band metasurface quasi-optical mode converter that converts cylindrical waveguide TE01 mode to circularly polarized Gaussian beam is designed and fabricated. Both electromagnetic simulation and experiment results show that the Gaussian beam can be observed from 35 to 38 GHz, corresponding to over 8.5% of the bandwidth. The maximum scalar Gaussian mode content of 97.85% is observed in the experiment, and the output radiation from the metasurface quasi-optical mode converter is approximate circular polarization. This work unveils the potential of compact quasi-optical mode converter based on metasurfaces.
Small molecule Y-320 stimulates ribosome biogenesis, protein synthesis, and aminoglycoside-induced premature termination codon readthrough
Authors: Hosseini-Farahabadi Sara , Baradaran-Heravi Alireza , Zimmerman Carla , Choi Kunho , Flibotte Stephane , Roberge Michel
Published: May 2021

Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the extent of PTC readthrough that can be achieved by aminoglycosides like G418. Using a cell-based screen, we identified a small molecule, the phenylpyrazoleanilide Y-320, that potently enhancesTP53,DMD, and COL17A1PTC readthrough by G418. Unexpectedly, Y-320 increased cellular protein levels and protein synthesis, measured by SYPRO Ruby protein staining and puromycin labeling, as well as ribosome biogenesis measured using antibodies to rRNA and ribosomal protein S6. Y-320 did not increase the rate of translation elongation and it exerted its effects independently of mTOR signaling. At the single cell level, exposure to Y-320 and G418 increased ribosome content and protein synthesis which correlated strongly with PTC readthrough. As a single agent, Y-320 did not affect translation fidelity measured using a luciferase reporter gene but it enhanced misincorporation by G418. RNA-seq data showed that Y-320 up-regulated the expression of CXC chemokines CXCL10, CXCL8, CXCL2, CXCL11, CXCL3, CXCL1, and CXCL16. Several of these chemokines exert their cellular effects through the receptor CXCR2 and the CXCR2 antagonist SB225002 reduced cellular protein levels and PTC readthrough in cells exposed to Y-320 and G418. These data show that the self-limiting nature of PTC readthrough by G418 can be compensated by Y-320, a potent enhancer of PTC readthrough that increases ribosome biogenesis and protein synthesis. They also support a model whereby increased PTC readthrough is enabled by increased protein synthesis mediated by an autocrine chemokine signaling pathway. The findings also raise the possibility that inflammatory processes affect cellular propensity to readthrough agents and that immunomodulatory drugs like Y-320 might find application in PTC readthrough therapy.
Extracting representations of cognition across neuroimaging studies improves brain decoding
Authors: Mensch Arthur , Mairal Julien , Thirion Bertrand , Varoquaux Gaël
Published: May 2021

Cognitive brain imaging is accumulating datasets about the neural substrate of many different mental processes. Yet, most studies are based on few subjects and have low statistical power. Analyzing data across studies could bring more statistical power; yet the current brain-imaging analytic framework cannot be used at scale as it requires casting all cognitive tasks in a unified theoretical framework. We introduce a new methodology to analyze brain responses across tasks without a joint model of the psychological processes. The method boosts statistical power in small studies with specific cognitive focus by analyzing them jointly with large studies that probe less focal mental processes. Our approach improves decoding performance for 80% of 35 widely-different functional-imaging studies. It finds commonalities across tasks in a data-driven way, via common brain representations that predict mental processes. These are brain networks tuned to psychological manipulations. They outline interpretable and plausible brain structures. The extracted networks have been made available; they can be readily reused in new neuro-imaging studies. We provide a multi-study decoding tool to adapt to new data.
Low rate of relapse after twelve-dose multidrug therapy for hansen’s disease: A 20-year cohort study in a brazilian reference center
Authors: Nery José A. C. , Sales Anna M. , Hacker Mariana A. V. B. , Moraes Milton O. , Maia Raquel C. , Sarno Euzenir N. , Illarramendi Ximena
Published: May 2021

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915–2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.
Measuring intellectual capital with financial data
Authors: Jardon Carlos M. , Martinez-Cobas Xavier
Published: May 2021

Intellectual capital is defined as the set of intangible assets that generate value for the company. Normally, the models that measure the intellectual capital make use of investments in intangible assets, as indicators of the generation of value by the company; or are based on a holistic measure, using another focus to validate. This research proposes a new method to measure intellectual capital, reconciling the use of financial measures for the management of intellectual capital and its antecedents in triangulated indices; it also determines relationship path coefficients, between constructs developed from a general conceptual model, based on the academic and professional literature. The proposed method combines component indicators with holistic indicators using a structural equation model, allowing differentiating the components of intellectual capital from the stock of intellectual capital. The method is applied to more than 1,600 European companies from 2004 to 2015 to assess its validity, presenting the monetary value of intellectual capital in these companies. The results allow a comparison of the situation of intellectual capital in companies in different countries and industries, opening an opportunity to disclosure intellectual capital.