bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Parameter Hardy Spaces Theory and Endpoint Estimates for Multi-Parameter Singular Integrals
Authors: Lu Guozhen , Shen Jiawei , Zhang Lu
Published: January 2023

The main purpose of this paper is to establish the theory of the multi-parameter Hardy spaces

H
p

H^p

(

0
>
p
≤
1

0>p\leq 1

) associated to a class of multi-parameter singular integrals extensively studied in the recent book of B. Street (2014), where the

L
p

L^p

(
1
>
p
>
∞
)

(1>p>\infty )

estimates are proved for this class of singular integrals. This class of multi-parameter singular integrals are intrinsic to the underlying multi-parameter Carnot-Carathéodory geometry, where the quantitative Frobenius theorem was established by B. Street (2011), and are closely related to both the one-parameter and multi-parameter settings of singular Radon transforms considered by Stein and Street (2011, 2012a, 2012b, 2013).

More precisely, Street (2014) studied the

L
p

L^p

(
1
>
p
>
∞
)

(1>p>\infty )

boundedness, using elementary operators, of a type of generalized multi-parameter Calderón Zygmund operators on smooth and compact manifolds, which include a certain type of singular Radon transforms. In this work, we are interested in the endpoint estimates for the singular integral operators in both one and multi-parameter settings considered by Street (2014). Actually, using the discrete Littlewood-Paley-Stein analysis, we will introduce the Hardy space

H
p

H^p

(

0
>
p
≤
1

0>p\leq 1

) associated with the multi-parameter structures arising from the multi-parameter Carnot-Carathéodory metrics using the appropriate discrete Littlewood-Paley-Stein square functions, and then establish the Hardy space boundedness of singular integrals in both the single and multi-parameter settings. Our approach is much inspired by the work of Street (2014) where he introduced the notions of elementary operators so that the type of singular integrals under consideration can be decomposed into elementary operators.
Picnic, Accident or Cookies? A Systematic Approach to Guide the Selection of the Picture Definition Tasks in Linguistic Assessment
Authors: Seçkin Mustafa , Savaş Merve
Published: January 2023

Objective

Picture description tasks are used to elicit language samples in individuals with aphasia and other cognitive disorders. However, task selection may affect the type of language variables elicited. In this study, our goal is to compare the strengths and the weaknesses of the two internationally used picture description tasks with a novel picture description task developed specifically for Turkish-speaking individuals.

Materials and methods

In sum, 20 cognitively healthy individuals with a mean age of 52 ± 14/3 were included. Three different picture description tasks composed of single pictures were used: The Picnic Scene from the Western Aphasia Battery-Revised, the Cookie Theft picture from the Boston Diagnostic Aphasia Examination and the Accident Scene from the Turkish Language Assessment Test for Aphasia. All language samples were recorded using a digital voice recorder. Automated and semi-automated approaches were used for the systematic analysis of the language features that were classified into four levels: general language measures, the morphosyntactic level, the lexicosemantic level and the sentence level.

Results

Participants showed greater efficiency and produced the greatest number of subordinate clauses, derivational suffixes, passive voice suffixes and relative past tense construction during the Accident Scene description. On the lexicosemantic level, the Picnic Scene was particularly superior to the Cookie Theft Picture in eliciting nouns. Imperfective aspect use was less frequent in the Accident Scene description.

Conclusion

All three tasks had limitations and advantages compared with each other. We recommend the development of novel picture description tasks that would be more effective in eliciting specific language features in Turkish-speaking individuals.
Effects of hempseed cake on ruminal fermentation parameters, nutrient digestibility, nutrient flow, and nitrogen balance in finishing steers
Authors: Winders Thomas M , Neville Bryan W , Swanson Kendall C
Published: January 2023

Five ruminally and duodenally cannulated red angus steers (n = 5; initial body weight [BW] = 542 kg, SD = 40 kg) were used in a three-period Youden square design consisting of three 21-d periods, three treatments, and five steers (one or two steers per treatment within each period) to evaluate the effect of feeding hempseed cake on ruminal fermentation parameters, organic matter (OM) intake, total tract nutrient digestion, and nitrogen (N) balance in steers fed finishing diets. The control (CON) diet contained 75% dry-rolled corn, 20% corn silage, and 5% supplement (DM basis). The dried corn distillers grains plus solubles (DDGS) and hempseed cake (HEMP) diets contained 55% dry-rolled corn, 20% corn silage, 20% dried corn distillers grains plus solubles or hempseed cake, and 5% supplement (DM basis). Total ruminal volatile fatty acid concentration was greater (P < 0.01) in steers fed the HEMP diet than in steers fed the DDGS or CON diets. Ruminal fluid pH was not influenced (P = 0.93) by treatment. Organic matter intake tended (P = 0.07) to be greater and OM total tract digestibility was less (P = 0.03) in steers fed the HEMP diet compared with steers fed the DDGS or CON diets. Ruminal true and total tract apparent N digestibility was greater (P < 0.01) in steers fed the HEMP diet than steers fed the DDGS or CON diets. Duodenal flow of essential, nonessential, and total amino acids was not influenced (P ≥ 0.37) by dietary treatment, but the lack of response was likely because ruminally degradable protein (RDP) supply exceeded the RDP requirement. Steers fed the HEMP diet had greater (P < 0.01) N retention (g/d) than steers fed the DDGS diet, which was greater (P < 0.01) than steers fed the CON diet, suggesting that feeding hempseed cake improved utilization of N. Although inclusion of hempseed cake decreased total tract OM digestibility compared with dried corn distillers grains or corn, improvements in N utilization suggest that hempseed cake could be a useful alternative feed ingredient for finishing cattle diets.
Effects of long-term postgastric infusion of casein or glutamic acid on small intestinal starch digestion and energy balance in cattle
Authors: Acharya Subash , Petzel Emily A , Hales Kristin E , Underwood Keith R , Swanson Kendall C , Bailey Eric A , Cammack Kristi M , Brake Derek W
Published: January 2023

The objective of this experiment was to evaluate effects of postruminal flows of casein or glutamic acid on small intestinal starch digestion and to quantify changes in energy and nutrient balance. Twenty-four steers (body weight = 179 ± 4 kg) were duodenally infused with raw cornstarch (1.46 ± 0.04 kg/d) and either 413 ± 7.0 g casein/d, 121 ± 3.6 g glutamic acid/d or water (control). Measures of small intestinal starch digestion and nutrient excretion were collected across 4 d after 42 d of infusion and measures of respiration via indirect calorimetry were collected across 2 d after 48 d of infusion. Ileal starch flow was least among calves provided casein, but ileal starch flow was not different between glutamic acid or control. Small intestinal starch digestion tended to be greatest among calves provided casein, least for glutamic acid and intermediate for control. Casein increased ileal flow of ethanol soluble oligosaccharides compared to glutamic acid and control. Large intestinal starch digestion was not different among treatments. By design, N intake was greatest among cattle provided casein, intermediate among calves provided glutamic acid and least for control. Nitrogen retention was greater in response to casein compared to control and glutamic acid. Intake of gross energy from feed was similar across treatments, and gross energy from infusate was greatest for casein, intermediate for glutamic acid and least for control. Variation in gross energy intake from feed resulted in no difference in overall gross energy intake across treatments. Similar to measures of small intestinal starch digestion and N retention, casein increased calories of digestible energy and metabolizable energy, compared to glutamic acid and control, which did not differ. Postruminal infusions did not influence methane production, but heat production was greatest in steers infused with casein, intermediate for steers provided glutamic acid, and least for control. Overall, amounts of energy retained by casein tended to be nearly 34% greater than control, but glutamic acid had no impact on energy balance. Improvement in small intestinal starch digestion in response to casein increased energy and N retained; however, glutamic acid did not influence small intestinal starch digestion and energy or N balance in cattle, which seems to suggest that responses in small intestinal starch digestion to greater postruminal flows of glutamic acid become refractory across greater durations of time.
Evaluation of growth performance, carcass characteristics, and methane and CO2 emissions of growing and finishing cattle raised in extensive or partial-intensive cow-calf production systems
Authors: Carlson Zachary E , McPhillips Levi J , Stowell Rick R , Erickson Galen E , Drewnoski Mary , MacDonald Jim C
Published: January 2023

An experiment was conducted over 2 yr to measure performance and greenhouse gas (GHG) emissions of weaned calves from two cow-calf production systems. Crossbred steers and heifers (n = 270, initial body weight (BW) = 207 kg, SD = 35) were used in a randomized complete block design, with treatments applied to the cow-calf system. Treatments were: 1) a traditional system consisting of April to June calving with smooth bromegrass pasture and grazed corn residue as forage resources (TRAD); 2) an alternative system consisting of July to September calving utilizing partial-drylot feeding, summer-planted oats, and corn residue grazing (ALT). Calves from both production systems were weaned at the same age and grown (diet NEg = 1.05 Mcal kg–1) for approximately 117 d. The calves then transitioned to a high-grain finishing diet (year 1: NEg = 1.32 Mcal kg–1; year 2: NEg = 1.39 Mcal kg–1) and fed to a targeted 1.52 cm backfat. Growth performance in the grower phase resulted in greater (P < 0.01) average daily gain (1.39 vs. 1.22 ± 0.02 kg), greater gain:feed (P < 0.01; 0.157 vs. 0.137 ± 0.003) for ALT calves compared to TRAD calves, However, a lower initial BW (P < 0.01; 185 vs. 229 ± 4.9 kg) resulted in a lower ending BW (P < 0.01; 347 vs. 371 ± 2.9 kg) for ALT calves compared to TRAD calves in spite of improved growth performance. In the finisher phase, ALT calves gained less (1.52 vs. 1.81 ± 0.218 kg; P = 0.02), were less efficient (0.139 vs. 173 ± 0.0151; P = 0.01) but exhibited similar hot carcass weights (HCW) (388 vs. 381 ± 3.8 kg; P = 0.14) compared to TRAD calves. Each pen of calves was put into a large pen-scale chamber that continuously measured carbon dioxide (CO2) and methane (CH4) for 5 d during the grower and finisher phases. The average CH4 and CO2 production per unit of feed intake was used to calculate total GHG emissions over the entire grower and finisher phase. Overall, there were no differences (P ≥ 0.17) between treatments for CH4 per day and per kilogram dry matter intake (DMI). However, ALT calves tended to produce less (P ≤ 0.10) CO2 per day and per kilogram DMI than TRAD calves. Overall, methane emissions were greater in ALT calves (110.7 vs. 92.2 ± 8.3 g CH4 kg–1 HCW; P = 0.04) than TRAD calves. The ALT calves required 27 additional days on feed to market, which resulted in more total CH4 per animal across the entire feeding period (P = 0.02) than TRAD calves. Production systems that reduce days to market to achieve similar HCW may reduce GHG emissions.
IPM Adoption and Impacts in the United States
Authors: Lane David E , Walker Tegan J , Grantham Deborah G
Published: January 2023

Increased Integrated Pest Management (IPM) adoption hinges not only on the future of innovative research, but also on the willingness of growers to adopt new IPM technologies. Adoption and diffusion of innovations can encounter many different challenges. By better understanding the drivers of and barriers to IPM adoption, future research, extension, and education can better target behavior change. This study sought to better understand the IPM adoption drivers and barriers, along with the impacts of IPM, from the perspective of state IPM coordinators via an online Qualtrics survey. These professionals have a statewide perspective on IPM adoption. There were 37 completed surveys out of 56 email survey invitations, a 66% response rate. Overall, the participants ranked ‘high cost of practice’ as the most critical barrier to IPM adoption. ‘Difficulty of implementation’ and ‘lack of awareness’ were also highly ranked as critical barriers to adoption. When asked about ways to increase IPM adoption, participants ranked ‘improved cost-benefit analysis’ as the most critically important. Overall, these findings demonstrate the importance of providing improved IPM economic cost-benefit analyses to accompany the promotion of new and existing IPM innovations. Furthermore, even though the results of this study suggest that the impact of the Regional IPM Centers has been increasing regional IPM coordination, communication, collaboration, and cooperation. These findings also suggest a need for more comprehensive extension and education programs to specifically address the perceived ‘high cost of practice,’ ‘difficulty of implementation’, and ‘lack of awareness’ by communicating improved IPM cost-benefit analyses.
The ethics of immigration: How biased is the field?
Authors: Dumitru Speranta
Published: January 2023

Methodological nationalism is the assumption that nation-states are the relevant units for analyzing social phenomena. Most of the social sciences recognized it as a source of bias, but not the ethics of immigration. Is this field biased by methodological nationalism—and if so, to what extent? This article takes nationalism as an implicit bias and provides a method to assess its depth. The method consists in comparing principles that ethicists commonly discuss when immigration is not at stake with principles advocated in the ethics of immigration. To interpret the results, a distinction between mild and heavy bias is established. When a basic principle in ethics is underdiscussed or absent from the ethics of immigration, the field is ‘mildly biased’. When its negation is commonly advocated, the field is ‘heavily biased’. Here, the method is illustrated with two principles: equal opportunity and reparation. They are common in theories of distributive justice and of corrective justice, respectively. But in the ethics of immigration, scholars often argue for the opposite. Instead of equal opportunity, they implicitly support discrimination based on national origin; instead of sanctions or amnesty for the offenders, scholars plead amnesty for those who they otherwise regard as victims. These preliminary results suggest that the field is heavily biased: methodological nationalism seems to turn ethics into its opposite.
Cepheid Metallicity in the Leavitt Law (C- MetaLL) survey – II. High-resolution spectroscopy of the most metal poor Galactic Cepheids
Authors: Trentin E , Ripepi V , Catanzaro G , Storm J , Marconi M , De Somma G , Testa V , Musella I
Published: January 2023

Classical Cepheids (DCEPs) are the first fundamental step in the calibration of the cosmological distance ladder. Furthermore, they represent powerful tracers in the context of Galactic studies. We have collected high-resolution spectroscopy with UVES@VLT for a sample of 65 DCEPs. The majority of them are the faintest DCEPs ever observed in the Milky Way. For each target, we derived accurate atmospheric parameters, radial velocities, and abundances for 24 different species. The resulting iron abundances range between +0.3 and −1.1 dex with the bulk of stars at [Fe/H] ∼ −0.5 dex. Our sample includes the most metal-poor DCEPs observed so far with high-resolution spectroscopy. We complement our sample with literature data obtaining a complete sample of 637 DCEPs and use Gaia Early Data Release 3 (EDR3) photometry to determine the distance of the DCEPs from the period–Wesenheit–Metallicity relation. Our more external data trace the Outer arm [at Galactocentric radius (RGC) ∼ 16–18 kpc] which appears significantly warped. We investigate the metallicity gradient of the Galactic disc using this large sample, finding a slope of −0.060 ± 0.002 dex kpc−1, in very good agreement with previous results based both on DCEPs and open clusters. We also report a possible break in the gradient at RGC = 9.25 kpc with slopes of −0.063 ± 0.007 and −0.079 ± 0.003 dex kpc−1 for the inner and outer sample, respectively. The two slopes differ by more than 1σ. A more homogeneous and extended DCEPs sample is needed to further test the plausibility of such a break.
Association Between Traumatic Brain Injury and Increased Risk of Stroke: A Systematic Review and Meta-analysis
Authors: Esterov Dmitry , Sperl Michael A. , Hines Emily A. , Kinzelman Vesely Elissa A. , Brown Allen W.
Published: January 2023

Objective:

To determine whether exposure to traumatic brain injury (TBI) is associated with increased risk of stroke in adults compared with referents not exposed to TBI, and to understand whether an association exists throughout the spectrum of injury severity, whether it differs between the acute and chronic phases after TBI, and whether the association is greater with hemorrhagic compared with ischemic stroke after TBI.

Setting:

A database search was conducted on January 22, 2021. Searches were run in MEDLINE (1946 to present), Embase (1988 to present), Evidence-Based Medicine Reviews (various dates), Scopus (1970 to present), and Web of Science (1975 to present).

Design:

Observational studies that quantified the association of stroke after TBI compared with referents without TBI were included. Three coauthors independently reviewed titles and abstracts to determine study eligibility. Study characteristics were extracted independently by 2 coauthors who followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and study quality was assessed independently by 2 coauthors who used the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed.

Main Measures:

The primary exposure was TBI of any severity, and the primary outcome was stroke of any kind. Subgroup analysis was performed to assess heterogeneity associated with severity of TBI, type of stroke, and time from TBI to stroke.

Results:

A total of 64 full-text articles were reviewed, and data were extracted from 8 cohort studies (N = 619 992 individuals exposed to TBI along with nonexposed referents). A significant overall association was found with TBI and stroke (hazard ratio, 2.06; 95% CI, 1.28-3.32). Significant subgroup differences were found with a smaller risk of ischemic stroke compared with stroke of all types (P < .001, I² = 93.9%).

Conclusions:

TBI, regardless of injury severity, was associated with a higher risk of stroke. To improve secondary stroke prevention strategies, future studies should classify TBI severity and type of stroke more precisely and determine long-term risk.
INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part I: Posttraumatic Amnesia
Authors: Ponsford Jennie , Trevena-Peters Jessica , Janzen Shannon , Harnett Amber , Marshall Shawn , Patsakos Eleni , Kua Ailene , McIntyre Amanda , Teasell Robert , Wiseman-Hakes Catherine , Velikonja Diana , Bayley Mark Theodore , McKay Adam
Published: January 2023

Introduction:

Posttraumatic amnesia (PTA) is a common occurrence following moderate to severe traumatic brain injury (TBI) and emergence from coma. It is characterized by confusion, disorientation, retrograde and anterograde amnesia, poor attention and frequently, agitation. Clinicians and family need guidelines to support management practices during this phase.

Methods:

An international team of researchers and clinicians (known as INCOG) met to update the INCOG guidelines for assessment and management of PTA. Previous recommendations and audit criteria were updated on the basis of review of the literature from 2014.

Results:

Six management recommendations were made: 1 based on level A evidence, 2 on level B, and 3 on level C evidence. Since the first version of INCOG (2014), 3 recommendations were added: the remainder were modified. INCOG 2022 recommends that individuals should be assessed daily for PTA, using a validated tool (Westmead PTA Scale), until PTA resolution. To date, no cognitive or pharmacological treatments are known to reduce PTA duration. Agitation and confusion may be minimized by a variety of environmental adaptations including maintaining a quiet, safe, and consistent environment. The use of neuroleptic medications and benzodiazepines for agitation should be minimized and their impact on agitation and cognition monitored using standardized tools. Physical therapy and standardized activities of daily living training using procedural and errorless learning principles can be effective, but delivery should be tailored to concurrent levels of cognition, agitation, and fatigue.

Conclusions:

Stronger recommendations regarding assessment of PTA duration and effectiveness of activities of daily living training have been made. Evidence regarding optimal pharmacological and nonpharmacological management of confusion and agitation during PTA remains limited, with further research needed. These guidelines aim to enhance evidence-based care and maximize consistency of PTA management.
Effects of Perceptual-motor Training on Collision Judgments with Peripheral Prism Expanded Vision
Authors: Houston Kevin Edward , Peli Eli , Luo Gang , Bowers Alex R. , Woods Russell L.
Published: January 2023

SIGNIFICANCE

Peripheral prisms (p-prisms) improve blind-side detection of hazards in hemianopia by shifting the image of the hazard into the intact visual field. Collision judgments can be made accurately after detection by using a gaze shift to fixate the hazard in the prism-free portion of the lens, but this is slow relative to normal peripheral vision. A prior study found that prism adaptation for visual direction did not occur with general wear. We developed a perceptual-motor training regimen that resulted in accurate pointing at p-prism targets after six 1-hour sessions.

PURPOSE

This study aimed to determine if improvements in pointing accuracy from perceptual-motor training generalized to collision judgments during simulated walking.

METHODS

Participants with hemianopia (n = 13) made collision judgments in virtual reality for a person appearing 0.4 to 13.5° from the walking path. Judgments were measured under fixed gaze, requiring collision judgments via the p-prism image only, and free gaze, representing a more natural scenario. Measurements were made without and with p-prisms immediately after fitting, after a 2-week acclimation, after training, and 3 months later. Controls (n = 13) did one visit without p-prisms.

RESULTS

Controls had 100% detection and symmetrically distributed collision judgments for the central 33 and 36% of hazards under fixed gaze and free gaze, respectively. In hemianopia, the seeing side was not different from controls. Blind-side detection was reduced without p-prisms to 40% fixed gaze and 82% free gaze and improved with p-prisms to 99% fixed gaze and 97% free gaze (P < .001). When first worn, fixed-gaze prism side collisions were 63 versus 37% on the seeing side and 41 versus 39% for free gaze (P < .001). There was a small improvement for fixed gaze after the 2-week acclimation (53%, P < .001), but no improvements from training or an additional 3 months of use.

CONCLUSIONS

P-prisms improved detection, but collision judgments were inaccurate when seen only via the p-prisms and did not improve with perceptual-motor training. Patients should continue to be advised to turn their head and eyes to fixate the hazard after detection.
Assessment of Low Vision Referrals before and after Establishment of a Low Vision Program at an Academic Medical Center
Authors: Dalzotto Katherine , Banghart Mark , Thomas-Virnig Christina , Mondal Sanbrita
Published: January 2023

SIGNIFICANCE

We assessed the number of referrals for low vision (LV) services to determine if establishing an LV program at a large academic medical center impacted referral rates. Visual acuity (VA), referral outcome, location, and specialty were examined as factors that could impact referrals.

PURPOSE

This study aimed to identify gaps in the referral process to LV services.

METHODS

Electronic medical records of patients were reviewed to ascertain the referral rate among those who qualified for services, both before (2014 to 2016) and after (2017 to 2019) the establishment of an LV program. The medical records were further subdivided into two categories based on VA in the better-seeing eye: 20/70 to 20/200 and 20/200 to worse vision.

RESULTS

A total of 2014 patient records with VA qualifying for LV services were reviewed. The proportion of patients who had a VA of 20/70 to 20/200 inclusive in their better eye was 91.7%. A majority (89.8%) of patients with VA of 20/70 to 20/200 and 74.4% of patients with VA worse than 20/200 were never referred. Before establishing an LV program, only 2.2% of patients with VA of 20/70 to 20/200 were referred for services on their first visit, which improved to 8% after the program was established (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.37 to 6.33;P< .001). Also, before the program's establishment, 12.5% of patients with VA worse than 20/200 were referred on their first visit, which increased to 31.9% after the program's establishment (OR, 3.29; 95% CI, 1.50 to 7.19;P= .002). Patients with VA worse than 20/200 were more likely to be referred (before: OR, 6.34 [95% CI, 3.03 to 13.28;P< .001]; after: OR, 5.38 [95% CI, 3.09 to 9.37;P< .001]). Our data also showed that 10.3% of patients in this study declined referral to LV services.

CONCLUSIONS

Referral rates to LV services are low among patients who qualify. The establishment of an LV program at the medical center significantly increased referral rates. However, more improvement is necessary to connect patients to LV services.
Acceptance of a Pre-visit Intervention to Engage African American Glaucoma Patients during Visits
Authors: Sleath Betsy , Carpenter Delesha M. , Davis Scott A. , Budenz Donald L. , Muir Kelly W. , Romero Maria S. , Lee Charles , Tudor Gail , Garcia Nacire , Adjei Abena A. , Robin Alan L.
Published: January 2023

SIGNIFICANCE

The glaucoma question prompt list/video intervention was well received by patients. Eighty-seven percent of patients recommended that other patients should watch the educational video before their visits, and 89% said that other patients should complete the question prompt list before visits.

PURPOSE

The objectives of this study were to (a) describe patient feedback on a glaucoma question prompt list/video intervention designed to motivate African American patients to be more engaged during visits and (b) examine patient demographics associated with acceptance of the intervention.

METHODS

We are conducting a randomized controlled trial of a glaucoma question prompt list/video intervention. African American patients with glaucoma were enrolled and assigned to a control group or an intervention group where they watched a video emphasizing the importance of asking questions and received a prompt list to complete before visits. All patients were interviewed after visits and are being followed up for 12 months.

RESULTS

One hundred eighty-nine African American patients with glaucoma were enrolled into the larger trial. Of the 93 patients randomized to the intervention group, 89% said that patients should complete the prompt lists before visits, and 87% recommended that patients should watch the video before visits. Older patients were significantly less likely to believe that other patients should watch the video before their visits (t = −3.7, P = .04). Patients with fewer years of education were significantly more likely to rate the video as being more useful than patients with more years of education (Pearson correlation, −0.27; P = .01). Patients who reported being less adherent on the visual analog scale were more likely to rate the video as being more useful (Pearson correlation, −0.23; P = .03).

CONCLUSIONS

This study demonstrates that the question prompt list/video was accepted by the majority of African American patients who received the intervention.
Impact of Viewing Conditions and Vision Anomalies on Accuracy and Dynamics of Noncycloplegic Autorefraction
Authors: Kiermasz Justyna , Sobol Maria , Pniewski Jacek
Published: January 2023

SIGNIFICANCE

This study was conducted to analyze the influence of binocular vision and accommodation anomalies on refraction dynamics. Our results may help to design more accurate autorefractors and to better understand the difficulties in prescribing an optical correction or adaptation to a correction.

PURPOSE

This study aimed to verify whether viewing conditions (open- or closed-field) or vision anomalies, such as ocular surface diseases, accommodative dysfunctions, and binocular vision anomalies, influence (1) the differences between subjective refraction and autorefraction and (2) the characteristics of the short-term refractive state variation.

METHODS

The subjective refraction of 64 subjects aged 23 to 60 years was measured during a comprehensive optometric examination, and the Ocular Surface Disease Index questionnaire was collected. Twenty successive measurements of automated refraction of each eye were obtained using a conventional autorefractor Nidek ARK-510A and an open-field autorefractor Shin-Nippon NVision-K 5001. Conventional notation of refractive error (sphere, cylinder, axis) was transformed to h-vectors, presented in scatterplots, and analyzed statistically.

RESULTS

The three-way analysis of variance tests showed that there is no influence of accommodation dysfunctions (P = .22 for ARK-510A), binocular vision anomalies (P = .97 for ARK-510A), and ocular surface diseases (P = .20 for ARK-510A) on differences between autorefraction and subjective refraction. The binocular vision anomalies affected the results from open-field autorefractor, whereas the accommodation impacted closed-field refraction measurements. Changes in short-term refractive state variation occurred in sphere power, indicating accommodative state changes; however, 30 subjects demonstrated at least one outlier and/or polymodality of refractive state distributions.

CONCLUSIONS

The study showed that the presence of accommodative dysfunctions or binocular vision anomalies might increase the range of short-term refractive state variation. The impact of vision anomalies differs between viewing conditions. The polymodal distribution of refractive state variation and the presence of outliers imply that automatic modes used typically in autorefractors with three to five readings may not accurately represent the refractive state of the eye.
Prevalence and Readmission Rates of Discharge Directly Home From the PICU: A Systematic Review
Authors: Daoust Daphne , Dodin Philippe , Sy Eric , Lau Vincent , Roumeliotis Nadia
Published: January 2023

OBJECTIVES:

Critically ill patients are increasingly being discharged directly home from PICU as opposed to discharged home, via the ward. The objective was to assess the prevalence, safety, and satisfaction of discharge directly home from PICUs.

DATA SOURCES:

We searched PubMed, Medline, EMBASE, PsycINFO, and CINAHL for studies published between January 1991 and June 2021.

STUDY SELECTION:

We included observational or randomized studies, of children up to 18 years old, that reported on the prevalence, safety, or satisfaction of discharge directly home from the PICU, compared with the ward. Safety outcomes included readmission, unplanned visits to hospital, and any adverse events. We excluded case series, reviews, and studies discharging patients to other facilities.

DATA EXTRACTION:

Two independent reviewers evaluated 88 full-text articles; five studies met eligibility (362,868 patients). Only one study had discharge directly home as a primary outcome.

DATA SYNTHESIS:

Prevalence of discharge directly to home from the PICU ranged from less than 1% to 23% (random effects proportion 7.7 [95% CI, 1.3–18.6]). Readmissions to the PICU (only safety outcome) were significantly lower in the discharge directly home group compared with the ward group, in two of three studies (p < 0.0001). No studies reported on patient or family satisfaction.

CONCLUSIONS:

The prevalence of discharge directly home from the PICU ranges from 1% to 23%. PICU readmission rates do not appear to increase after discharge directly home. Caution is needed in the interpretation of the results, given the significant heterogeneity of the included studies. Further high-quality studies are needed to evaluate the safety of discharge directly home from the PICU and support families in this transition.
Brief Report: Does Menopause Transition Influence Viral Suppression and Adherence in Women Living With HIV?
Authors: Hachfeld Anna , Atkinson Andrew , Stute Petra , Calmy Alexandra , Tarr Philip E. , Darling Katharine E.A. , Babouee Flury Baharak , Polli Christian , Sultan-Beyer Leila , Abela Irene A. , Aebi-Popp Karoline ,   the Swiss HIV Cohort Study (SHCS)
Published: January 2023

Background:

Increasing numbers of women living with HIV transition through menopause. It is unclear whether this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities, or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU).

Setting:

Retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018.

Methods:

We explored perimenopausal and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities, and IDU using interrupted time series models.

Results:

Rates of depression and psychiatric care increased during perimenopause before decreasing afterward. Negative treatment outcomes such as viral blips, low-level viremia, viral failure, and low adherence steadily declined while transitioning through menopause—this was also true for subgroups of women with depression, psychiatric treatment, and active IDU.

Conclusions:

Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland.
Transitions across Kidney Disease Stages and Association with New-onset Heart Failure: a Population-Based study of 8569 Individuals and 12.6 Years of Follow-up
Authors: Chen Yuntao , Bakker Stephan JL , Suthahar Navin , Meems Laura M.G. , Groothof Dion , van Veldhuisen Dirk J. , van Gilst Wiek H. , de Boer Rudolf A , Gansevoort Ron T , Lunter Gerton , Hillege Hans L. , Postmus Douwe
Published: January 2023

Background

Limited data exist on transitions across Kidney Disease Improving Global Outcomes (KDIGO) risk stages and association with new-onset heart failure (HF) in the general population.

Methods

Data were extacted from the first four clinical examinations of the PREVEND study. Participants were categorized into eGFR and albuminuria risk stages according to KDIGO Guideline. Multi-state model was fitted to estimate the transition rates across consecutive KDIGO risk stages and the association with new-onset HF.

Results

8569 participants were included at baseline. During a median follow-up of 12.6 years, 373 participants were diagnosed with new-onset HF and 710 participants had died before new-onset HF. The transition rate from low risk to intermediate risk stage did not differ between women and men; it increased from 0 to 10 transitions per 100 person-years from age 50 to 75 years. The transition rate from intermediate risk to high or very high risk stage increased exponentially with age, with women having lower rates (HR: 0.50, 95%CI: 0.34-0.76). Younger subjects and women were more likely to make a backward transition from intermediate risk to low risk stage. More advanced KDIGO risk stages were associated with increased risk of new-onset HF, and the risk association attenuates with age on the relative scale but strengthens with age on the absolute scale.

Conclusions

Slowing the progression of KDIGO risk stages may result in an important reduction in the incidence of new-onset heart failure in this population of middle-aged subjects.
iCVS - Inferring Cardio-Vascular hidden States from physiological signals available at the bedside
Authors: Ravid Tannenbaum Neta , Gottesman Omer , Assadi Azadeh , Mazwi Mjaye , Shalit Uri , Eytan Danny
Published: January 2023

Intensive care medicine is complex and resource-demanding. A critical and common challenge lies in inferring the underlying physiological state of a patient from partially observed data. Specifically for the cardiovascular system, clinicians use observables such as heart rate, arterial and venous blood pressures, as well as findings from the physical examination and ancillary tests to formulate a mental model and estimate hidden variables such as cardiac output, vascular resistance, filling pressures and volumes, and autonomic tone. Then, they use this mental model to derive the causes for instability and choose appropriate interventions. Not only this is a very hard problem due to the nature of the signals, but it also requires expertise and a clinician’s ongoing presence at the bedside. Clinical decision support tools based on mechanistic dynamical models offer an appealing solution due to their inherent explainability, corollaries to the clinical mental process, and predictive power. With a translational motivation in mind, we developed iCVS: a simple, with high explanatory power, dynamical mechanistic model to infer hidden cardiovascular states. Full model estimation requires no prior assumptions on physiological parameters except age and weight, and the only inputs are arterial and venous pressure waveforms. iCVS also considers autonomic and non-autonomic modulations. To gain more information without increasing model complexity, both slow and fast timescales of the blood pressure traces are exploited, while the main inference and dynamic evolution are at the longer, clinically relevant, timescale of minutes. iCVS is designed to allow bedside deployment at pediatric and adult intensive care units and for retrospective investigation of cardiovascular mechanisms underlying instability. In this paper, we describe iCVS and inference system in detail, and using a dataset of critically-ill children, we demonstrate its use and power to identify bleeding, distributive states, and cardiac dysfunction, in isolation and in combination.

Author summary

A common challenge clinicians face across different disciplines is estimating the hidden physiological state of a patient based on partially observed data. Here we describe iCVS (inferring Cardio-Vascular States): a dynamical mechanistic model of the cardiovascular system. We developed iCVS with a translational goal in mind, showing high explanatory power, its inference relies only on routinely available signals, and enables the identification of various clinically important shock states. We demonstrate the use of the model on a dataset that was collected in a pediatric intensive care unit.
Clarifying the biological and statistical assumptions of cross-sectional biological age predictors
Authors: Sluiskes Marije H. , Goeman Jelle J. , Beekman Marian , Slagboom P. Eline , Putter Hein , Rodríguez-Girondo Mar
Published: January 2023

There is variability in the rate of aging among people of the same chronological age. The concept of biological age is postulated to capture this variability, and hence to better represent an individual’s true global physiological state than chronological age.

Biological age predictors are often generated based on cross-sectional data, using biochemical or molecular markers as predictor variables. It is assumed that the difference between chronological and predicted biological age is informative of one’s chronological age-independent rate of aging Δ.

We show that the most popular cross-sectional biological age predictors—based on multiple linear regression, the Klemera-Doubal method or principal component analysis—rely on the same strong underlying assumption, namely that a candidate marker of aging’s association with chronological age is directly informative of its association with the aging rate Δ. We call this the identical-association assumption and prove that it is untestable in a cross-sectional setting. Using synthetic data, we illustrate the consequences if the assumption does not hold: in such scenarios, there is no guarantee that the weights that a cross-sectional method assigns to candidate markers are informative of the underlying truth. Using real data we illustrate that the extent to which the identical-association assumption holds is of direct practical relevance for anyone interested in developing or interpreting cross-sectional biological age predictors.
E3 Ubiquitin Ligase CHIP Drives Monoubiquitination-mediated Nuclear Import of Tumor Suppressor PTEN
Authors: Chakraborty Shrabastee , Karmakar Subhajit , Basu Malini , Ghosh Mrinal K.
Published: January 2023

Nuclear localization of Phosphatase and Tensin Homolog Deleted on Chromosome TEN (PTEN) is crucial for its tumor suppressive activities. Monoubiquitination has been established as a principal mechanism driving nuclear translocation of PTEN. In this study, we describe a novel mechanism wherein Carboxy terminus of Hsc70 Interacting Protein (CHIP) mediates monoubiquitination of PTEN, leading to the latter’s nuclear import. Analysis of subcellular fractions of multiple cell lines revealed a rise in both nuclear and total cellular PTEN levels under monoubiquitination-promoting conditions, an effect that was abrogated when CHIP expression was silenced. We established a time-point kinetics of CHIP-mediated nuclear translocation of PTEN using immunocytochemistry. We identified a role of Karyopherin α1 (KPNA1) in facilitating nuclear transport of monoubiquitinated PTEN. We further established a direct interaction between CHIP and PTEN inside the nuclear compartment, where CHIP could participate in either polyubiquitination or monoubiquitination of the latter. CHIP was found to monoubiquitinate PTEN on K13 and K289 residues. Finally, we showed that CHIP-mediated monoubiquitination of PTEN resulted in increased apoptosis, decreased cell viability and proliferation. This enhancement of PTEN’s tumor suppressive abilities by CHIP involved modulation of transcriptional activities of PTEN. To the best of our knowledge, this is the first report elucidating CHIP’s non-canonical roles on PTEN, which is also established here as a nuclear interacting partner of CHIP.
Time Dependent Dihedral Angle Oscillations of the Spike Protein of SARS-CoV-2 Reveal Favored Frequencies of Dihedral Angle Rotations
Authors: Bastidas Oscar
Published: January 2023

The spike protein of SARS-CoV-2 is critical to viral infection of host cells which ultimately results in COVID-19. In this study we analyze the behavior of dihedral (phi and psi) angles of the spike protein over time from molecular dynamics and identify that the oscillations of these dihedral angles are dominated by a few discrete, relatively low frequencies in the 23-63 MHz range with 42.96875 MHz being the most prevalent frequency sampled by the oscillations. We further observe that upon tallying the populations of each individual frequency for all residues along the frequency spectrum, there is a regular alternation between high and low population counts along the increasing frequency values in the spectrum. This alternation of the counts becomes less pronounced and ultimately stabilizes as the frequency values increase. These observations thus suggest a regularity and propensity in the spike protein’s dihedral angles to avoid similar oscillation population counts between vicinal frequencies. We also observe that for amino acids that are least abundant in the S protein, there are certain frequencies at which the dihedral angles never oscillate, in contrast to relatively abundant amino acids that ultimately cover the entire spectrum. This suggests that the frequency components of dihedral angle oscillations may also be a function of position in the primary structure: the more positions an amino acid is found in, the more frequencies it can sample. Lastly, certain residues identified in the literature as constituting the inside of a druggable pocket of the spike protein, as well as other residues identified as allosteric sites, are observed in our data to have distinctive time domain profiles. This motivates us to propose residues from our dynamic data, with similar time domain profiles, which may be of potential interest to the vaccine and drug design communities, for further investigation. Thus our findings indicate that there is a particular frequency domain profile for the spike protein, hidden within the time domain data, and this information, perhaps with the suggested residues, might provide additional insight into therapeutic development strategies for COVID-19 and beyond.
Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis
Authors: Dave Biren M. , Chen Xin , McCready Fraser , Tailor Jignesh K. , Ellis James , Huang Xi , Dirks Peter B.
Published: January 2023

Cerebellar granule neurons (CGNs) are the most abundant neurons in the human brain and modulate cerebellar output to the motor cortex. Dysregulation of CGN development underlies movement disorders and medulloblastomas. It is suspected that these disorders arise in progenitor states of the CGN lineage, for which human models are lacking. Here, we have differentiated human hindbrain neuroepithelial stem (hbNES) cells to CGNsin vitrousing soluble growth factors, recapitulating key progenitor states in the lineage. We show that hbNES cells are not lineage committed and retain rhombomere 1 (r1) regional identity. Upon differentiation, hbNES cells first transit through a rhombic lip (RL) progenitor state at day 7, demonstrating human specific sub-ventricular cell identities. This RL state is followed by an ATOH1+CGN progenitor state at day 14. By the end of a 56-day differentiation procedure, we obtain mature neurons expressing CGN markers GABAAa6 and vGLUT2. These neurons generate spontaneous and evoked action potentials. A small fraction of endpoint neurons were unipolar brush cells (UBC). We noted maintenance of a RL population throughout differentiation, as is consistent with human development. We show that sonic hedgehog (SHH) promotes γ-aminobutyric acid (GABA)-ergic lineage specification and is a positive regulator of CGN progenitor proliferation. Interestingly, we observed that functional neuronal maturation is impaired by either elevated or absent SHH signaling. Impaired maturation under high SHH levels represents the potential of our system to model cerebellar tumorigenesis. Further, our data suggest a potential pro-differentiation role of SHH within a certain concentration range. Our work is, to our knowledge, the first detailed temporal characterization of the complete human CGN lineagein vitro. Our system recapitulates developmentally relevant progenitor states and is a new tool to model this specific cerebellar lineage, and how it may be disrupted to cause human disease.