bluuebunny/crossref_metadata_2025 huggingface dataset:
Short tandem repeat expansions in cortical layer‐specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder
Authors: Kim Jae Hyun , Koh In Gyeong , Lee Hyeji , Lee Gang‐Hee , Song Da‐Yea , Kim Soo‐Whee , Kim Yujin , Han Jae Hyun , Bong Guiyoung , Lee Jeewon , Byun Heejung , Son Ji Hyun , Kim Ye Rim , Lee Yoojeong , Kim Justine Jaewon , Park Jung Woo , Kim Il Bin , Choi Jung Kyoon , Jang Ja‐Hyun , Trost Brett , Lee Junehawk , Kim Eunjoon , Yoo Hee Jeong , An Joon‐Yong
Published: May 2024

Aim

Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes.

Methods

We analyzed WGS data of 634 ASD families and performed genome‐wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD‐associated STR loci.

Results

In ASD cases, rare STR expansions predominantly occurred in early cortical layer‐specific genes involved in neurodevelopment, highlighting the cellular specificity of STR‐associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD‐associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non‐carriers.

Conclusion

Short tandem repeat expansions in cortical layer‐specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under‐investigated population.
Cross‐attention neural network for land cover change detection with remote sensing images
Authors: Lv Zhiyong , Zhong Pingdong , Wang Wei , Sun Weiwei , Lei Tao , Nicola Falco
Published: May 2024

Land cover change detection (LCCD) with remote sensing images (RSIs) is important for observing the land cover change of the Earth's surface. Considering the insufficient performance of the traditional self‐attention mechanism used in a neural network to smoothen the noise of LCCD with RSIs, in this study a novel cross‐attention neural network (CANN) was proposed for improving the performance of LCCD with RSIs. In the proposed CANN, a cross‐attention mechanism was achieved by employing another temporal image to enhance attention performance and improve detection accuracies. First, a feature difference module was embedded in the backbone of the proposed CANN to generate a change magnitude image and guide the learning progress. A self‐attention module based on the cross‐attention mechanism was then proposed and embedded in the encoder of the proposed network to make the network pay attention to the changed area. Finally, the encoded features were decoded to obtain binary change detection with the ArgMax function. Compared with five methods, the experimental results based on six pairs of real RSIs well demonstrated the feasibility and superiority of the proposed network for achieving LCCD with RSIs. For example, the improvement for overall accuracy for the six pairs of real RSIs improved by our proposed approach is about 0.72–2.56%.
The long wavelength limit of periodic solutions of water wave models
Authors: Bona J. L. , Chen H. , Hong Y. , Panthee M. , Scialom M.
Published: May 2024

The present essay is concerned with providing rigorous justification of a long‐standing practice in numerical simulation of partial differential equations. Theory often sets initial‐value problems on all of or . If the initial data are localized in space, it has been usual practice to approximate the problem by an associated periodic problem or a homogeneous Dirichlet problem set on a finite interval. While these strategies are commonplace, rigorous justification of the practice is sparse. It is our purpose here to indicate justification of this practice in the concrete context of a surface water wave model. While the theory worked out here is specific to the particular partial differential equation, it will be apparent to the reader that more general results may be derived using the same approach.
Semiparametric efficient estimation in high‐dimensional partial linear regression models
Authors: Fu Xinyu , Huang Mian , Yao Weixin
Published: May 2024

We introduce a novel semiparametric efficient estimation procedure for high‐dimensional partial linear regression models to overcome the challenge of efficiency loss of the traditional least‐squares based estimation procedure under unknown error distributions, while enjoying several appealing theoretical properties. The new estimation procedure provides a sparse estimator for the parametric component and achieves the semiparametric efficiency as the oracle maximum likelihood estimator as if the error distribution was known. By employing the penalized estimation and the semiparametric efficiency theory for ultra‐high‐dimensional partial linear model, the procedure enjoys the oracle variable selection property and offers efficiency gain for non‐Gaussian random errors, while maintaining the same efficiency as the least squares‐based estimator for Gaussian random errors. Extensive simulation studies and an empirical application are conducted to demonstrate the effectiveness of the proposed procedure.
Temporal dynamics of in vitro hemostatic function in platelets cryopreserved using a novel approach for rapid issuance
Authors: Kwan Patrick S. L. , Kirwan Susy , Tuinukuafe Alice , Morley Sarah
Published: May 2024

Background

Current procedures for thawing and issuing of cryopreserved platelets (CPPs) are laborious and have remained challenging in emergency settings such as blood banks and military operations. In this prospective study, a novel processing method designed to facilitate the rapid issuance of CPPs with no postthaw handling required was developed and functionally characterized in parallel with standard CPPs manufactured.

Study Design and Methods

Double‐dose plateletpheresis units (n = 42) were cryopreserved at −80°C in 5%–6% dimethyl sulfoxide to produce matched pairs thawed successively over a 27‐month period for comparison between two processing arms. In contrast to the standard CPPs manufactured as standalone units, platelets were frozen in tandem with resuspending plasma in a distinct partition as a single unit in the novel method, herein referred to as tandem CPPs. Postthaw (PT) CPPs from both arms were assessed at PT0‐, 12‐, and 24‐h to measure platelet recovery, R‐time (time to clot initiation; min), and maximum amplitude (MA; clot strength; mm) using thromboelastography.

Results

In the overall dataset, mean platelet recovery was higher (p < .0005) for tandem CPPs (83.9%) compared with standard CPPs (73.3%) at PT0; mean R‐times were faster (p < .0005) for tandem CPPs (2.5–3.6 min) compared with standard CPPs (3.0–3.8 min); mean MA was higher for tandem CPPs (57.8–59.5 mm) compared with standard CPPs (52.1–55.8 mm) at each postthaw time point (p < .05).

Conclusion

Robust temporal dynamics of superior hemostatic functionality were established for tandem CPPs over extended cryopreservation up to 27 months and 24 h of postthaw storage.
Reducing blood product wastage through the inter‐hospital redistribution of near‐outdate inventory
Authors: Hajjaj Omar I. , Modi Dimpy , Cameron Tracy , Barty Rebecca , Owens Wendy , Heddle Nancy , Zhang Liying , Thompson Troy , Callum Jeannie
Published: May 2024

Background

Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage.

Study Design

A province‐wide redistribution program was designed and implemented to redistribute near‐outdate plasma protein and related blood products from low‐usage to high‐usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost‐analysis was performed to determine the effectiveness of this redistribution program.

Results

A total of 130 hospital transfusion services contributed at least one near‐outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non‐compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure.

Conclusion

Redistributing near‐outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products.
Generation of broadband optical chaos at mid-infrared wavelength with an interband cascade laser
Authors: Spitz O. , Shuai Y. B. , Zhao S. , Didier P. , Díaz-Thomas D. A. , Baranov A. N. , Cerutti L. , Rontani D. , Wu J. , Grillot F.
Published: May 2024

Nonlinear dynamics at mid-infrared wavelength is of interest for various applications but has been mainly limited to quantum cascade lasers so far. In this article, we show that interband cascade lasers can generate complex optical chaos with bandwidth in the GHz range and this outperforms the performances of quantum cascade laser chaos. The chaos nature of our signal is confirmed by a thorough time-series analysis. Modeling of the semiconductor laser under short-cavity external optical feedback allows confirming the high bias chaos operation that we observe experimentally. These results pave the way for applications at mid-infrared wavelength, such as private free-space communication.
Nonlinear oscillatory rheology of aqueous suspensions of cellulose nanocrystals and nanofibrils
Authors: Xu Jiatong , Wang Pengguang , Zhou Ziyu , Yuan Baihua , Zhang Hongbin
Published: May 2024

In this work, the nonlinear rheological behavior of aqueous suspensions composed of two typical nanocellulose [rod-like cellulose nanocrystals (CNCs) and filamentous cellulose nanofibrils (CNFs)] was examined and compared by using various large-amplitude oscillatory shear (LAOS) analysis methods, such as Fourier-transform rheology, stress decomposition, Chebyshev polynomials, and the sequence of physical processes. From our analysis, the nonlinear rheological parameters of higher harmonics, dissipation ratio, strain hardening ratio, shear thickening ratio, transient modulus, and cage modulus were obtained and quantitatively analyzed. CNCs tend to assemble to form anisotropic structures in an aqueous medium while the CNFs are entangled to form gels. The CNF suspensions demonstrated a significant viscous modulus overshoot and had stronger yield stresses, but the yield of CNC suspensions was more ductile. In the case of low concentrations, the CNF suspensions demonstrated stronger intracycle shear thickening behavior in medium-amplitude oscillatory shear region and lower dissipation ratios at small strain amplitudes. Although both nanocellulose suspensions revealed the existence of four intracycle rheological transition processes (viscoplastic deformation, structural recovery, early-stage yielding, and late-stage yielding), the CNF suspensions exhibited a stronger structural recovery ability. Larger strain amplitudes did not invariably result in a broader range of intracycle rheological transitions, which are also affected by the excitation frequency. The application of the various LAOS analysis methods provided valuable intracycle nonlinear rheological insights into nanocellulose suspensions, which are of great importance for enhancing their industrial perspectives.
Swim, Strength, or Combined Programs: Effect on Health-Related Physical Fitness in Adolescents With Down Syndrome
Authors: Suarez-Villadat Borja , Sadarangani Kabir , Corredeira Rui Manuel , Veiga Mario , Villagra Ariel
Published: May 2024

The adolescent population with Down syndrome (DS) appears to show higher levels of body fat and lower levels of cardiorespiratory fitness or muscle strength than their peers without disabilities. There is a need to create physical activity programs to improve these data. The aim of this research was to determine the effects of a 16-week swimming program, strength program, and combined program (swimming and strength training) on body composition and health-related physical fitness on adolescents with DS and to assess whether there are differences in the results of the different training programs. Forty-five adolescents (17 female and 28 male; average age 15.5 [1.53] years) with DS were recruited and randomized to three groups (swim [n = 15], strength [n = 15], and combined [n = 15]). Results showed that the swim group had significant improvements in all health-related physical fitness variables and there was an improvement in some body-composition variables (p < .05). The strength and combined groups obtained minor improvements in the variables analyzed. In summary, a 16-week swim program consisting of three sessions of 60 min is able to improve levels of body composition and health-related physical fitness in adolescents with DS. The swim training program seems to be more effective in improving body composition and health-related physical fitness than the strength or combined program. These findings could be useful in different special-education centers due to the predisposition shown by the population with DS to this sport modality.
From a Junior Coach to the Senior Ranks: Relational Transition From a Collaborative Autoethnographic Perspective
Authors: Nikander Jaakko A.O. , Ryba Tatiana V.
Published: May 2024

Coaches are key people influencing athletes’ careers and their development, especially when athletes approach the junior-to-senior transition. Junior-to-senior mobility also includes transitioning into a new psychosocial environment, including changes in cultural narratives and expectations for both an athlete and their coach. The purpose of this study was to contribute knowledge about a sports coach’s career development and transitions by theorizing a relational co-construction of transitions from the junior level to the senior level. The cultural transition model was used as a conceptual framework to explore the temporality of the first author’s (Jakob) relational transition. To coproduce Jakob’s story, a collaborative autoethnographic approach was utilized. A photo-elicitation method and cyclical interviewing were used to generate the data followed by a thematic narrative analysis. The results indicated that the dominant narratives of elite sport and relation to the athlete shaped Jakob’s subject position, from which he projected his future career as a coach during the transition. Central to relational transition is the understanding that the meaning (re)construction and negotiation of cultural practices occur through interactions with repositioning. The subjective repositioning of both the athlete and the coach can impact the dynamics and outcomes of the transition process.
Mandating Women Board Members in Sport Organizations: Change via Coercive Institutional Pressure
Authors: Wilson Kathleen B. , Karg Adam , Sherry Emma , Symons Kasey , Breitbarth Tim
Published: May 2024

Boosting board representation of women redresses structural unfairness and improves corporate governance and performance. The Change Our Game initiative, running over 3 years statewide in Victoria, Australia, mandated 40% representation of women on state sport boards. At the start, only 44% of state sport boards had 40% women representation; by the mandate deadline, this had increased to 93%. Using an institutional theory lens, the authors qualitatively analyzed four stakeholder groups: mandators, policy champions, operationalists, and mandate targets. Stakeholder sentiments were analyzed pre- and postmandate deadline over 3 years. Sentiments ranged from positive to equivocation to denigration. The mandate’s coercive pressure, supported by institutional legitimacy and work to accelerate changes, led to institutional change and achieved a significant increase in women board members. Change was grounded in strong ethical and cognitive support from mandate champions. Microsocial expressions of denigration and change resistance did not prevent successful change.
It’s Complicated: Examining Connections Between Emotions and Career Stages Among Physical Educators
Authors: Gaudreault Karen Lux , Schulz Denis , Simonton Kelly , Richards Kevin Andrew , Mercier Kevin
Published: May 2024

Background: Physical education (PE) is a marginalized profession that is socially and emotionally demanding. PE teachers are prone to early career attrition, isolation, and burnout as a result of negative emotional experiences. While these outcomes are customary, little is known about how teachers’ emotions change across their careers. The purpose of this study was to explore the relationship between PE Teacher Career Stages and their emotional experiences. Methods: Participants included 31 in-service PE teachers (Mage = 44.70 years, SD = 9.48; M = 15.87 years of teaching) from the United States. Inductive and deductive analyses were used to evaluate the interview data. Results: Themes included: (a) teachers identify within multiple stages/emotions, (b) stakeholder agendas cultivate negative emotions, and (c) the aftermath of the pandemic as a catalyst for frustration. Conclusion: Teachers’ emotions are complex and multidimensional. Exploring teachers’ emotions within different career stages may help prevent early career attrition and increase job satisfaction.
An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery
Authors: Huang Qin , Chan Ken Y. , Wu Jason , Botticello-Romero Nuria R. , Zheng Qingxia , Lou Shan , Keyes Casey , Svanbergsson Alexander , Johnston Jencilin , Mills Allan , Lin Chin-Yen , Brauer Pamela P. , Clouse Gabrielle , Pacouret Simon , Harvey John W. , Beddow Thomas , Hurley Jenna K. , Tobey Isabelle G. , Powell Megan , Chen Albert T. , Barry Andrew J. , Eid Fatma-Elzahraa , Chan Yujia A. , Deverman Benjamin E.
Published: May 2024

Developing vehicles that efficiently deliver genes throughout the human central nervous system (CNS) will broaden the range of treatable genetic diseases. We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human
TFRC
knockin mice. The enhanced tropism was CNS-specific and absent in wild-type mice. When used to deliver
GBA1
, mutations of which cause Gaucher disease and are linked to Parkinson’s disease, BI-hTFR1 substantially increased brain and cerebrospinal fluid glucocerebrosidase activity compared with AAV9. These findings establish BI-hTFR1 as a potential vector for human CNS gene therapy.
Tracking the tempo of a continental margin arc: Insights from a forearc succession in West Antarctica
Authors: Riley Teal R. , Flowerdew Michael J. , Carter Andrew , Curtis Michael L. , Millar Ian L. , Crame J. Alistair , Whitehouse Martin J.
Published: May 2024

The Fossil Bluff Group of eastern Alexander Island records the exceptional preservation of more than 8 km of Mesozoic sedimentary rocks deposited into an accretionary forearc basin that developed unconformably above a late Paleozoic accretionary complex, and in proximity to a continental margin arc during a prolonged phase of enhanced magmatism. Through the Mesozoic, the Fossil Bluff Group evolved from a trench-slope environment to a forearc basin sourced from the continental margin arc. During this period, the Antarctic Peninsula’s convergent margin was characterized by episodes of magmatic flare-ups that developed during tectonic compression, crustal thickening, extension, and uplift. U-Pb and Lu-Hf detrital zircon data are used to determine the provenance of the forearc succession and as a monitor of arc magmatic tempos during the late Mesozoic. The magmatic record in the adjacent arc is poorly preserved or partially absent, but the sedimentary record of the forearc basin preserves a largely uninterrupted record of arc magmatism that can be studied with detrital zircon geochronology and geochemistry. The basal succession of the Fossil Bluff Group is sourced from the adjacent accretionary complex, but thereafter it is strongly controlled by the proximal arc in western Palmer Land and is characterized by a mixed arc/recycled signature during episodes of renewed sedimentation. However, the main phases of deposition during the Early Jurassic (ca. 180 Ma), Early Cretaceous (141–131 Ma), and mid-Cretaceous (125–102 Ma) are dominated by arc-only sources. The Lu-Hf isotopic record supports a transition from convergence to extension and a return to convergence during the Mesozoic, which is consistent with accretionary orogens from elsewhere along the West Gondwanan margin. The provenance record during the depositional history of the basin points overwhelmingly to an autochthonous origin; as such, models for parts of the western province of the Antarctic Peninsula being allochthonous are unsupported.
Noncommutative Geometry of Random Surfaces
Authors: Okounkov Andrei
Published: May 2024

We associate a noncommutative curve to a periodic, bipartite, planar dimer model with polygonal boundary. It determines the inverse Kasteleyn matrix and hence all correlations. It may be seen as a quantization of the limit shape construction of Kenyon and the author. We also discuss various directions in which this correspondence may be generalized.
Preparation of High-Labeled Graphene Oxide by Tritium Thermal Activation Method for Application in the Betavoltaic Cell of a Nuclear Battery
Authors: Badun G. A. , Bunyaev V. A. , Chernysheva M. G.
Published: May 2024

The possibility of tritium introduction into graphene oxide (GO) by tritium thermal activation method was demonstrated. It was established that, in order to produce the highest possible specific radioactivity, thin films of GO with a thickness of 5.6 mg/m2 must be treated with tritium atoms. The experiment conducted at 77 K showed a number of advantages. GO was processed with tritium atoms, the resulting specific activity of [3H]GO reached 2.6 Ci/mg in term of the weight of the initial GO (0.7 Ci/mg after removal of the labile tritium). Specific energy release of [3H]GO with this specific activity is 22.3 W/kg, which is quite sufficient for its application as a component of a nuclear battery.
Nanodiamonds as Lutetium-177 Carriers for Nuclear Medicine
Authors: Kazakov A. G. , Babenya J. S. , Ekatova T. Y. , Vinokurov S. E. , Khvorostinin E. Y. , Ushakov I. A. , Zukau V. V. , Stasyuk E. S. , Nesterov E. A. , Sadkin V. L. , Rogov A. S. , Myasoedov B. F.
Published: May 2024

The work investigated the sorption of no-carrier-added 177Lu isolated from neutron-irradiated 176Yb2O3, and carrier-added 177Lu obtained by irradiation of natLu2O3, by commercial and oxidized nanodiamonds (NDs) of various grades from aqueous solutions to identify among them a promising carrier for further research in the field of nuclear medicine. A promising sorbent was found: oxidized NDs of the STP grade (ox-STP); conditions for the fast sorption of lutetium with it in an amount equivalent to 1.2 GBq of no-carrier-added 177Lu were determined, which corresponds to the activity used in therapy.
Clinical and healthcare use outcomes after cessation of long term opioid treatment due to prescriber workforce exit: quasi-experimental difference-in-differences study
Authors: Sabety Adrienne H , Neprash Hannah T , Gaye Marema , Barnett Michael L
Published: May 2024

Objective

To examine the association between prescriber workforce exit, long term opioid treatment discontinuation, and clinical outcomes.

Design

Quasi-experimental difference-in-differences study

Setting

20% sample of US Medicare beneficiaries, 2011-18.

Participants

People receiving long term opioid treatment whose prescriber stopped providing office based patient care or exited the workforce, as in the case of retirement or death (n=48 079), and people whose prescriber did not exit the workforce (n=48 079).

Main outcomes

Discontinuation from long term opioid treatment, drug overdose, mental health crises, admissions to hospital or emergency department visits, and death. Long term opioid treatment was defined as at least 60 days of opioids per quarter for four consecutive quarters, attributed to the plurality opioid prescriber. A difference-in-differences analysis was used to compare individuals who received long term opioid treatment and who had a prescriber leave the workforce to propensity-matched patients on long term opioid treatment who did not lose a prescriber, before and after prescriber exit.

Results

Discontinuation of long term opioid treatment increased from 132 to 229 per 10 000 patients who had prescriber exit from the quarter before to the quarter after exit, compared with 97 to 100 for patients who had a continuation of prescriber (adjusted difference 1.22 percentage points, 95% confidence interval 1.02 to 1.42). In the first quarter after provider exit, when discontinuation rates were highest, a transient but significant elevation was noted between the two groups of patients in suicide attempts (adjusted difference 0.05 percentage points (95% confidence interval 0.01 to 0.09)), opioid or alcohol withdrawal (0.14 (0.01 to 0.27)), and admissions to hospital or emergency department visits (0.04 visits (0.01 to 0.06)). These differences receded after one to two quarters. No significant change in rates of overdose was noted. Across all four quarters after prescriber exit, an increase was reported in the rate of mental health crises (0.39 percentage points (95% confidence interval 0.08 to 0.69)) and opioid or alcohol withdrawal (0.31 (0.014 to 0.58)), but no change was seen for drug overdose (−0.12 (−0.41 to 0.18)).

Conclusions

The loss of a prescriber was associated with increased occurrences of discontinuation of long term opioid treatment and transient increases in adverse outcomes, such as suicide attempts, but not other outcomes, such as overdoses. Long term opioid treatment discontinuation may be associated with a temporary period of adverse health impacts after accounting for unobserved confounding.
Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study
Authors: Falcaro Milena , Soldan Kate , Ndlela Busani , Sasieni Peter
Published: May 2024

Objectives

To replicate previous analyses on the effectiveness of the English human papillomavirus (HPV) vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) using 12 additional months of follow-up, and to investigate effectiveness across levels of socioeconomic deprivation.

Design

Observational study.

Setting

England, UK.

Participants

Women aged 20-64 years resident in England between January 2006 and June 2020 including 29 968 with a diagnosis of cervical cancer and 335 228 with a diagnosis of CIN3. In England, HPV vaccination was introduced nationally in 2008 and was offered routinely to girls aged 12-13 years, with catch-up campaigns during 2008-10 targeting older teenagers aged <19 years.

Main outcome measures

Incidence of invasive cervical cancer and CIN3.

Results

In England, 29 968 women aged 20-64 years received a diagnosis of cervical cancer and 335 228 a diagnosis of CIN3 between 1 January 2006 and 30 June 2020. In the birth cohort of women offered vaccination routinely at age 12-13 years, adjusted age standardised incidence rates of cervical cancer and CIN3 in the additional 12 months of follow-up (1 July 2019 to 30 June 2020) were, respectively, 83.9% (95% confidence interval (CI) 63.8% to 92.8%) and 94.3% (92.6% to 95.7%) lower than in the reference cohort of women who were never offered HPV vaccination. By mid-2020, HPV vaccination had prevented an estimated 687 (95% CI 556 to 819) cervical cancers and 23 192 (22 163 to 24 220) CIN3s. The highest rates remained among women living in the most deprived areas, but the HPV vaccination programme had a large effect in all five levels of deprivation. In women offered catch-up vaccination, CIN3 rates decreased more in those from the least deprived areas than from the most deprived areas (reductions of 40.6%
v
29.6% and 72.8%
v
67.7% for women offered vaccination at age 16-18 and 14-16, respectively). The strong downward gradient in cervical cancer incidence from high to low deprivation in the reference unvaccinated group was no longer present among those offered the vaccine.

Conclusions

The high effectiveness of the national HPV vaccination programme previously seen in England continued during the additional 12 months of follow-up. HPV vaccination was associated with a substantially reduced incidence of cervical cancer and CIN3 across all five deprivation groups, especially in women offered routine vaccination.
Enhancing SARS-CoV-2 surveillance in Malawi using telephone syndromic surveillance from July 2020 to April 2022
Authors: Woelk Godfrey , Maphosa Thulani , Machekano Rhoderick , Chauma-Mwale Annie , Makonokaya Lucky , Zimba Suzgo B , Chamanga Rachel Kanyenda , Nyirenda Rose , Auld Andrew , Kim Evelyn , Sampathkumar Veena , Ahimbisibwe Allan , Kalitera Louiser , Kim Lindsay , Maida Alice
Published: May 2024

Introduction

Monitoring the SARS-CoV-2 pandemic in low-resource countries such as Malawi requires cost-effective surveillance strategies. This study explored the potential utility of phone-based syndromic surveillance in terms of its reach, monitoring trends in reported SARS-CoV-2-like/influenza-like symptoms (CLS/ILS), SARS-CoV-2 testing and mortality.

Methods

Mobile phone-based interviews were conducted between 1 July 2020 and 30 April 2022, using a structured questionnaire. Randomly digital dialled numbers were used to reach individuals aged ≥18 years who spoke Chichewa or English. Verbal consent was obtained, and trained research assistants with clinical and nursing backgrounds collected information on age, sex, region of residence, reported CLS/ILS in the preceding 2 weeks, SARS-CoV-2 testing and history of household illness and death. Data were captured on tablets using the Open Data Kit database. We performed a descriptive analysis and presented the frequencies and proportions with graphical representations over time.

Findings

Among 356 525 active phone numbers, 138 751 (38.9%) answered calls, of which 104 360 (75.2%) were eligible, 101 617 (97.4%) consented to participate, and 100 160 (98.6%) completed the interview. Most survey respondents were aged 25–54 years (72.7%) and male (65.1%). The regional distribution of the respondents mirrored the regional population distribution, with 45% (44%) in the southern region, 41% (43%) in the central region and 14% (13%) in the northern region. The reported SARS-CoV2 positivity rate was 11.5% (107/934). Of the 7298 patients who reported CLS/ILS, 934 (12.8%) reported having undergone COVID-19 testing. Of the reported household deaths, 47.2% (982 individuals) experienced CLS/ILS 2 weeks before their death.

Conclusion

Telephonic surveillance indicated that the number of SARS-CoV-2 cases was at least twice as high as the number of confirmed cases in Malawi. Our findings also suggest a substantial under-reporting of SARS-CoV-2-related deaths. Telephonic surveillance has proven feasible in Malawi, achieving the ability to characterise SARS-CoV-2 morbidity and mortality trends in low-resource settings.
Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study
Authors: Ederoth Per , Grins Edgars , Dardashti Alain , Brondén Björn , Metzsch Carsten , Erdling André , Nozohoor Shahab , Mokhtari Arash , Hansson Magnus J , Elmér Eskil , Algotsson Lars , Jovinge Stefan , Bjursten Henrik
Published: May 2024

Introduction

Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia–reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia–reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI.

Methods and analysis

Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15–90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury.

Ethics and dissemination

The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study.

Trial registration number

NCT02397213; Pre-results.
Longitudinal study of cardiometabolic risk from early adolescence to early adulthood in an ethnically diverse cohort
Authors: Harding Seeromanie , Silva Maria João , Molaodi Oarabile R , Enayat Zinat E , Cassidy Aidan , Karamanos Alexis , Read Ursula M , Cruickshank J Kennedy
Published: May 2024

Objective

To examine influences of adiposity from early adolescence to early 20s on cardiovascular disease (CVD) risk in the multiethnic Determinants of young Adult Social well-being and Health (DASH) longitudinal study.

Methods

In 2002–2003, 6643 11–13-year-olds from 51 London schools participated at baseline, and 4785 were seen again at 14–16 years. Recently, 665 (97% of invited) participated in pilot follow-up at 21–23 years, with biological and psychosocial measures and blood biomarkers (only at 21–23 years). Regression models examined interplay between ethnicity, adiposity and CVD.

Results

At 21–23 years, ∼30–40% were overweight. About half of the sample had completed a degree with little ethnic variation despite more socioeconomic disadvantage in adolescence among ethnic minorities. Regardless of ethnicity, overweight increased more steeply between 14–16 years and 21–23 years than between 11–13 years and 14–16 years. More overweight among Black Caribbean and Black African females, lower systolic blood pressure (sBP) among Indian females and Pakistani/Bangladeshi males compared with White UK peers, persisted from 11–13 years. At 21–23 years, glycated haemoglobin (HbA1c) was higher among Black Caribbean females, total cholesterol higher and high-density lipoprotein (HDL) cholesterol lower among Pakistani/Bangladeshis. Overweight was associated with a ∼+2 mm Hg rise in sBP between 11–13 years and 21–23 years. Adiposity measures at 11–13 years were related to allostatic load (a cluster of several risk markers), HbA1c and HDL cholesterol at 21–23 years. Ethnic patterns in CVD biomarkers remained after adjustments.

Conclusions

Adolescent adiposity posed significant risks at 21–23 years, a period in the lifespan generally ignored in cardiovascular studies, when ethnic/gender variations in CVD are already apparent.
Development of an evidence-based complex intervention for community rehabilitation of patients with hip fracture using realist review, survey and focus groups
Authors: Roberts Jessica Louise , Din Nafees Ud , Williams Michelle , Hawkes Claire A , Charles Joanna M , Hoare Zoe , Morrison Val , Alexander Swapna , Lemmey Andrew , Sackley Catherine , Logan Phillipa , Wilkinson Clare , Rycroft-Malone Jo , Williams Nefyn H
Published: May 2024

Objectives

To develop an evidence and theory-based complex intervention for improving outcomes in elderly patients following hip fracture.

Design

Complex-intervention development (Medical Research Council (MRC) framework phase I) using realist literature review, surveys and focus groups of patients and rehabilitation teams.

Setting

North Wales.

Participants

Surveys of therapy managers (n=13), community and hospital-based physiotherapists (n=129) and occupational therapists (n=68) throughout the UK. Focus groups with patients (n=13), their carers (n=4) and members of the multidisciplinary rehabilitation teams in North Wales (n=13).

Results

The realist review provided understanding of how rehabilitation interventions work in the real-world context and three programme theories were developed: improving patient engagement by tailoring the intervention to individual needs; reducing fear of falling and improving self-efficacy to exercise and perform activities of daily living; and coordination of rehabilitation delivery. The survey provided context about usual rehabilitation practice; focus groups provided data on the experience, acceptability and feasibility of rehabilitation interventions. An intervention to enhance usual rehabilitation was developed to target these theory areas comprising: a physical component consisting of six additional therapy sessions; and a psychological component consisting of a workbook to enhance self-efficacy and a patient-held goal-setting diary for self-monitoring.

Conclusions

A realist approach may have advantages in the development of evidence-based interventions and can be used in conjunction with other established methods to contribute to the development of potentially more effective interventions. A rehabilitation intervention was developed which can be tested in a future randomised controlled trial (MRC framework phases II and III).

Trial registration number

ISRCTN22464643, Pre-results.
Comprehensive analysis of vitreous specimens for uveitis classification: a prospective multicentre observational study
Authors: Maruyama Kazuichi , Inaba Tohru , Sugita Sunao , Ichinohasama Ryo , Nagata Kenji , Kinoshita Shigeru , Mochizuki Manabu , Nakazawa Toru
Published: May 2024

Purpose

To determine the clinical relevance of vitreous biomarkers in patients with uveitis.

Design

Multicentre, prospective, observational study.

Setting

Uveitis outpatient clinics of two academic medical centres in Japan.

Patient population

This study included 234 eyes of 191 patients with various uveitis aetiologies: definitive sarcoidosis (61 eyes of 46 patients), suspected sarcoidosis (60 eyes of 45 patients), intraocular tumour (34 eyes of 27 patients), viral infection (20 eyes of 18 patients), non-sarcoidosis (16 eyes of 16 patients) and unknown aetiology (43 eyes of 39 patients).

Observation procedure

Vitreous samples (taken by pars planta vitrectomy) were analysed with flow cytometry, cytology and multiplex PCR analysis.

Main outcome measures

The primary outcome measures were the diagnostic values of various biomarkers (T cells, B cells and pathogen DNA) in vitreous samples. The secondary outcome was visual acuity after vitrectomy.

Results

Sarcoidosis showed higher CD4/CD8 or CD4+measurements than other aetiologies (p<0.01). In samples with viral infection, pathogen DNA was detected, and CD8+counts were higher than the other aetiologies (p<0.01). Eyes with tumour had higher CD19+(p<0.05). Non-sarcoidosis had lower CD4/CD8 than sarcoidosis, higher CD8+than sarcoidosis and lower CD19+than tumour (p<0.01). Unknown uveitis had lower CD4/CD8 than sarcoidosis (p<0.01), and higher CD4/CD8 than non-sarcoidosis, viral infection or tumour (p<0.001). Visual acuity improved after vitrectomy (p<0.001).

Conclusions

Uveitis aetiologies had distinct vitreous biomarker profiles, especially of infiltrating lymphocytes. Analyses of CD4/CD8 ratio, T-lymphocyte and B-lymphocyte subset, and pathogen DNA in vitreous samples have good safety profiles and high diagnostic value for uveitis classification.

Trial registration number

UMIN000004980; Pre-results.
Psychoeducational intervention for people at high risk of developing another melanoma: a pilot randomised controlled trial
Authors: Dieng Mbathio , Kasparian NA , Mireskandari Shab , Butow Phyllis , Costa Daniel , Morton Rachael , Mann Graham , Menzies Scott , Cust Anne
Published: May 2024

Introduction

Information and psychological needs have been reported as one of the greatest areas of unmet needs for patients with melanoma. To respond to these needs, we developed theMelanoma Care Intervention,a developed psychoeducational intervention for people at high risk of developing another melanoma comprising of a newly developed melanoma educational booklet and individually tailored telephone support sessions provided by trained psychologists. The purpose of this study was to investigate the acceptability and feasibility of theMelanoma Care Intervention.

Methods

Twenty-four adults (14 men, 10 women, mean age: 58 years, SD: 12.2) at high risk of developing a subsequent primary melanoma were recruited and randomly assigned 1:1 to the intervention (a psychoeducational booklet, a Cancer Council booklet on melanoma and up to five telephone-based sessions with a psychologist) or usual care (Cancer Council booklet only). Acceptability, feasibility, fear of cancer recurrence and secondary psychosocial outcomes were assessed at baseline, 1 and 6 months.

Results

Satisfaction and perceived benefits were rated highly for all intervention components, particularly the telephone-based psychology sessions (mean satisfaction and benefits: both 9.27 out of 10, SD=2.41). The quality of information and support provided throughout the trial was rated as ‘high’ by the intervention group, with a mean score of 4.6 out of a possible 5 (SD=0.9) and 4.2 (SD=1.2) for the control group.

Conclusions

The intervention was feasible and acceptable for improving psychological adjustment. Timely access to effective, evidence-based, psychological care is a recognised need for people with melanoma. The intervention is designed to directly address this need in a way that is feasible in a clinical setting, acceptable to patients and health professionals.

Trial registration number

The trial was registered with the Australian and New Zealand Clinical Trials Registry on 19/03/2013 (Registration Number: ACTRN12613000304730).
101: PROLEGOMENA TO A TRUE INTEGRATIVE MEDICAL PARADIGM
Authors: Daneshfard Babak , Sanaye Reza , Nimrouzi Majid
Published: May 2024

When a paradigm starts to show signs of failure to cope with significant questions in any basic/applied branch of human knowledge, there come on the scene those who have perused the related literature enough to either answer those major questions according to the established paradigm or proffer a (wholly) new way of looking at things. In the latter case, the history of science tells us, aparadigm shifttakes place. Modern medicine cannot be proven to be totally disconnected from its traditional roots. Where traditional medicine came to give its place to present-day conventional medicine, a number of humanistic aspects of healing in addition to some axioms of olden wisdom were actually lost. Employing a personalized strategy by taking into account the patient's specific conditions, Integrative Medicine (IM) endeavours to apply all appropriate interventions from a whole set of science branches to bring back health. However, this does not remain fully without its own challenges from almost all sides. Complementary and Alternative Medicine (CAM) on the one hand, and: Evidence Based Medicine (EBM), on the other, have their own rightful say in the affair. Delving deep into the details of medical history's ups and downs, and examining –from the philosophy of medicine's and philosophy of science's standpoint– the pros and cons of integrative medicine, this present treatise makes a systemic, inter-disciplinary effort to put forward the best possible paradigmatology in a methodical way as far as the demands of society are concerned.
120: THE CLINICAL EFFECTIVENESS AND COST-EFFECTIVENESS OF FRACTIONAL CO2 LASER IN ACNE SCARS AND SKIN REJUVENATION: A SYSTEMATIC REVIEW AND ECONOMIC EVALUATION
Authors: Yaaghoobian Barmak , Sadeghi-Ghyassi Fatemeh , Hajebrahimi Sakineh
Published: May 2024

Background and aims:

Skin rejuvenation is one of high demand cosmetic interventions in Iran. Fractional CO2 Laser is a high power ablative laser which has variety of utilization in medicine including treatment of acne scars and rejuvenation. The aim of this study was to evaluate the safety, efficacy, and cost-effectiveness of Fractional CO2 Laser in comparison with other methods of rejuvenation and acne scar treatment.

Methods:

A systematic database search including Medline (via OVID and PubMed), EMBASE, CINHAL, Cochrane Library, CRD, SCOPUS and Web of Science conducted. After screening search results, selected publications appraised by CASP and Cochrane Collaboration's tool for assessing risk of bias and eligible studies included in the systematic review. In economic evaluation, all costs and benefits analyzed from Iran ministry of health's perspective.

Results:

From 2667 publications, two randomized control trials were eligible and included in the study. The affectivity and complications of Fractional CO2 laser were comparable with Er: YAG but Fractional CO2 laser was 14.7% (P=0.01) more effective than Q-Switched ND: YAG laser. Cost affectivity of this method was the same as other alternative lasers.

Conclusions:

Fractional CO2 laser is an effective and safe method for curing several kinds of skin. Never the less there was not sufficient evidence to support its advantage. This device has equal or lower price in comparison to competent technologies except for the non- fractional ablative Co2 laser that has the same or lower price and comparable effects.