bluuebunny/crossref_metadata_2025 huggingface dataset:
Annual Research Review: Mapping the multifaceted approaches and impacts of adverse childhood experiences – an umbrella review of meta‐analyses
Authors: Kim Bitna , Royle Meghan
Published: May 2024

Adverse childhood experiences (ACEs) significantly impact lifelong health and well‐being. Despite extensive research, a comprehensive understanding of ACEs' multifaceted impacts continues to be challenging to achieve. This study synthesizes meta‐analytic evidence to provide a comprehensive view of ACEs' effects, addressing various approaches to conceptualizing ACEs and their diverse outcomes. Employing an umbrella synthesis methodology, this review integrated findings from 99 meta‐analyses involving 592 effect sizes. We examined ACEs through specificity, lumping, dimensional, and child maltreatment‐centric approaches, assessing their impact across six domains: biological system dysregulation, neuropsychological impairments, physical health complications, mental health conditions, social and behavioral challenges, and criminal justice involvement. The findings reveal a small to moderate overall effect size of ACEs across outcome domains. Specific ACE approaches exhibited varying impact levels, with notable differences in effects on mental health, social/behavioral issues, and criminal justice involvement. When ACEs were aggregated without distinguishing between different types, but with consideration of their cumulative effects, adverse outcomes were significantly exacerbated. The child maltreatment‐centric approach consistently demonstrated substantial effects across all evaluated domains. This review underscores the heterogeneity in ACEs' impacts, influenced by the type of ACE and specific outcomes considered. It highlights the necessity for comprehensive approaches to understanding, preventing, and mitigating the effects of ACEs. These insights are vital for developing targeted interventions and informing policy‐making, emphasizing the complexity and varied nature of ACEs' influence on individual development and societal well‐being.
Digital workflow for prosthetic management of malpositioned implant in an adolescent patient: A 20‐year follow‐up
Authors: Alghamdi Mohanned , Kudara Yukio , Bokhary Abdullah , Papathanasiou Aikaterini , Papaspyridakos Panos
Published: May 2024

Objective

Dental implants placed in adolescent patients pose a challenge to restore and maintain an esthetic outcome over longer period of follow‐up. Maxillomandibular changes throughout adulthood may lead to complications such as implant infraocclusion and interproximal contact loss. This case report describes an alternate prosthetic treatment strategy for maxillary single implant placed in an adolescent patient in the esthetic zone with inappropriate implant axis and screw hole placement.

Clinical considerations

With temporary restorations, the gingiva and soft tissues were shaped to imitate the emerging profile of the contralateral side. A zirconia screw‐retained abutment was customized as a copy‐mirror from the contralateral prepared tooth to mimic the exact shape and to avoid labiolingual over contour by computer‐aided design/computer‐assisted manufacture (CAD/CAM). The porcelain laminate veneer was bonded to the zirconia abutment. Porcelain adhesive approach was used instead of traditional principles of retention and resistance form of the abutment.

Conclusions

A functional and esthetic outcome was achieved and maintained, while a minimally invasive procedure was implemented to use the malplaced implant instead of explanting it.

Clinical significance

The present report illustrates the prosthetic management of a malpositioned dental implant placed 20 years ago, utilizing a minimally invasive digital protocol.
A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family
Authors: Theuriet Julian , Marte Sheila , Isapof Arnaud , de Becdelièvre Alix , Konyukh Marina , Laureano‐Figueroa Stephanie M. , Latour Philippe , Quadrio Isabelle , Maisonobe Thierry , Antonellis Anthony , Stojkovic Tanya
Published: May 2024

Background and Aims

Pathogenic variants in the NARS1 gene, which encodes for the asparaginyl‐tRNA synthetase1 (NARS1) enzyme, were associated with complex central and peripheral nervous system phenotypes. Recently, Charcot–Marie–Tooth (CMT) disease has been linked to heterozygous pathogenic variants in NARS1 in nine patients. Here, we report two brothers and their mother from a French family with distal hereditary motor neuropathy (dHMN) carrying a previously unreported NARS1 variant.

Methods

The NARS1 variant (c.1555G>C; p.(Gly519Arg)) was identified through whole‐genome sequencing (WGS) performed on the family members. Clinical findings, nerve conduction studies (NCS), needle electromyography (EMG), and functional assays in yeast complementation assays are reported here.

Results

The family members showed symptoms of dHMN, including distal weakness and osteoarticular deformities. They also exhibited brisk reflexes suggestive of upper motor neuron involvement. All patients were able to walk independently at the last follow‐up. NCS and EMG confirmed pure motor neuropathy. Functional assays in yeast confirmed a loss‐of‐function effect of the variant on NARS1 activity.

Interpretation

Our findings expand the clinical spectrum of NARS1‐associated neuropathies, highlighting the association of NARS1 mutations with dHMN. The benign disease course observed in our patients suggests a slowly progressive phenotype. Further reports could contribute to a more comprehensive understanding of the spectrum of NARS1‐associated neuropathies.
Methods and theory for analyzing intensive longitudinal data in family research
Authors: Barber Jennifer S. , Liao Tim Futing
Published: May 2024

Although family scholars have long relied on longitudinal data, electronic methods of data collection like web‐ and app‐based surveys have greatly increased the amount of data with many repeated measures at short intervals, sometimes called intensive longitudinal data. The authors provide a conceptual overview of this type of data, paying particular attention to the appropriate frequency for the intervals, and discuss some of the unique contributions to Life Course Theory that can be generated with such data. They illustrate two analytic techniques that especially benefit from an intensive longitudinal design—sequence analysis and between‐within regression—by applying these methods to intensive longitudinal data from the Relationship Dynamics and Social Life Study that represent a “micro life course” of pregnancy risk (partnering, pregnancy desire, sex, and contraception) during the transition to adulthood. Their sequence analysis shows that singlehood, hormonal contraception, or partnered abstinence dominated most young women's micro‐life courses. Black/African‐American young women's micro life courses were similarly dominated by singlehood but were even more frequently dominated by partnered abstinence than their non‐Black/African‐American peers'. However, Black/African‐American women's micro life courses were less stable, potentially explaining their higher undesired pregnancy rates. A between‐within regression model shows that Black/African‐American coital contraceptors were less likely than their non‐Black/African‐American peers to use withdrawal (rather than condoms). They conclude by suggesting some potential ways that intensive longitudinal data capturing micro‐life courses can contribute to important outstanding research questions in family research.
Second‐best socially optimal R&D under output spillovers
Authors: Badra Yassine , Gaumont Damien , Halmenschlager Christine
Published: May 2024

Using the standard two‐stage game of process R&D and Cournot competition with R&D output spillovers, this paper provides a thorough second‐best welfare analysis. The planner's solution is compared with the standard noncooperative scenario, the R&D cartel, the cartelized research joint venture, and the social research joint venture solution in terms of propensities for R&D as well as welfare levels. The main result is that, when spillovers are not too high, a cartelized joint venture unexpectedly outperforms the planner's solution in terms of propensities for R&D and resulting welfare level, though it is the only market scenario to do so. We also assess the performance of a social joint venture, relative to all the well‐known scenarios for the organization of R&D. Finally, we observe that the gap between market outcomes and planner's solutions, in terms of welfare levels, increases as R&D becomes less appropriable.
Current research insights into the role of CTLA‐4 in hepatitis B virus (HBV) infection
Authors: Gu Qi , Yin Shengxia , Tong Xin , Rui Fajuan , Zhu Yixuan , Ma Xiaoyan , Huang Rui , Wu Chao , Li Jie
Published: May 2024

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV‐specific T cells, which is regulated by various co‐suppressor molecules. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is among these co‐suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV‐specific T cells. CTLA‐4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA‐4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA‐4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA‐4 may contribute to HBV infection, as well as the development of HBV‐induced cirrhosis and hepatocellular carcinoma.
Exploring interspecific hybridization dynamics in artificial forests of Pinus brutia and P. halepensis: Implications for sustainable afforestation
Authors: Houminer Naomi , Osem Yagil , Riov Joseph , Sherman Amir , Rozen Ada , Sela Hanan , David‐Schwartz Rakefet
Published: May 2024

Interspecific hybridization increases genetic diversity, which is essential for coping with changing environments. Hybrid zones, occurring naturally in overlapping habitats of closely related species, can be artificially established during afforestation. The resulting interspecific hybridization may promote sustainability in artificial forests, particularly in regions facing degradation due to climate change. Currently, there is limited evidence of hybridization during regeneration of artificial forests. Here, we studied the frequency of Pinus brutia Ten. × P. halepensis Mill. hybridization in five planted forests in Israel in three stages of forest regeneration: seeds before dispersal, emerged seedlings and recruited seedlings at the end of the dry season. We found hybrids on P. brutia, but not on P. halepensis trees due to asynchronous cone production phenology. Using 94 single‐nucleotide polymorphism (SNP) markers, we found hybrids at all stages, most of which were hybrids of advanced generations. The hybrid proportions increased from 4.7 ± 2.1 to 8.2 ± 1.4 and 21.6 ± 6.4 per cent, from seeds to emerged seedlings and to recruited seedlings stages, respectively. The increased hybrid ratio implies an advantage of hybrids over P. brutia during forest regeneration. To test this hypothesis, we measured seedling growth rate and morphological traits under controlled conditions and found that the hybrid seedlings exhibited selected traits of the two parental species, which likely contributed to the fitness and survival of the hybrids during the dry season. This study highlights the potential contribution of hybrids to sustainable‐planted forests and contributes to the understanding of genetic changes that occur during the regeneration of artificial forests.
Multiple regulatory inputs including cell envelope stress orchestrate expression of the Escherichia coli rpoN operon
Authors: Sikora Florian , Budja Lara Veronika Perko , Milojevic Olja , Ziemniewicz Amelia , Dudys Przemyslaw , Görke Boris
Published: May 2024

The rpoN operon, an important regulatory hub in Enterobacteriaceae, includes rpoN encoding sigma factor σ54, hpf involved in ribosome hibernation, rapZ regulating glucosamine‐6‐phosphate levels, and two genes encoding proteins of the nitrogen‐related phosphotransferase system. Little is known about regulatory mechanisms controlling the abundance of these proteins. This study employs transposon mutagenesis and chemical screens to dissect the complex expression of the rpoN operon. We find that envelope stress conditions trigger read‐through transcription into the rpoN operon from a promoter located upstream of the preceding lptA‐lptB locus. This promoter is controlled by the envelope stress sigma factor E and response regulator PhoP is required for its full response to a subset of stress signals. σE also stimulates ptsN‐rapZ‐npr expression using an element downstream of rpoN, presumably by interfering with mRNA processing by RNase E. Additionally, we identify a novel promoter in the 3′ end of rpoN that directs transcription of the distal genes in response to ethanol. Finally, we show that translation of hpf and ptsN is individually regulated by the RNA chaperone Hfq, perhaps involving small RNAs. Collectively, our work demonstrates that the rpoN operon is subject to complex regulation, integrating signals related to envelope stress and carbon source quality.
Integrating different facets of diversity into food web models: how adaptation among and within functional groups shape ecosystem functioning
Authors: Wojcik Laurie Anne , Klauschies Toni , Velzen Ellen van , Guill Christian , Gaedke Ursula
Published: May 2024

Adaptation of communities to environmental fluctuations can emerge from different facets of biodiversity, which may impact ecosystem functioning differently. Previous work in the field of biodiversity–ecosystem functioning (BEF) examined how ecosystem functions can be influenced by two sources of adaptive potential: sorting – i.e. changes in community composition due to fitness differences – can occur when multiple species or groups are present (richness), and trait adaptability – i.e. trait adjustments within species or functional groups – can emerge from genetic or phenotypic diversity. However, their effect is typically studied separately, and often in the context of only one trophic level. Therefore, we used a trait‐based, multispecies predator–prey model to investigate how sorting and trait adaptability, at one or two trophic levels, separately or jointly shape ecosystem functions and properties, such as total biomass, production, biomass‐weighted mean trait, relative top–down control and synchrony. We found that the adaptive potential emerging from any facet of diversity induced changes in trophic interactions, in turn affecting biomass distributions within and across trophic levels, dynamical behaviour, and synchrony of biomass dynamics within a trophic level. Particularly, sorting and trait adaptability could contribute to a similar degree and at a similar time to temporal changes in ecosystem functions, but their respective contribution depended on the speed of trait adaptation, the trait range between similar functional groups and trophic interactions. We thus suggest to consider multiple facets of diversity and their corresponding sources of adaptive potential to deepen our mechanistic understanding of BEF relationships, especially in the context of rapid biodiversity change.
Surgical Treatment Outcomes of Anterior‐Only Correction and Reconstruction for Severe Cervical Kyphotic Deformity with Neurofibromatosis‐1: A Retrospective Study with a 5‐Year Follow‐Up
Authors: Li Qiujiang , Wang Liang , Yang Huiliang , Yang Xi , Liu Limin , Wang Lei , Song Yueming
Published: May 2024

Objectives

Currently, anterior‐only (AO), posterior‐only, and combined anterior–posterior spinal fusions are common strategies for treating cervical kyphosis in patients with neurofibromatosis‐1 NF‐1. Nevertheless, the choice of surgical strategy remains a topic of controversy. The aim of our study is to evaluate the safety and effectiveness of anterior decompression and spinal reconstruction for the treatment of cervical kyphosis in patients with NF‐1.

Methods

Twelve patients with NF‐1‐associated cervical kyphotic deformity were reviewed retrospectively between January 2010 and April 2020. All patients underwent AO correction and reconstruction. The X‐ray was followed up in all these patients to assess the preoperative and postoperative local kyphosis angle (LKA), the global kyphosis angle (GKA), the sagittal vertical axis, and the T1 slope. The visual analog scale score, Japanese Orthopedic Association (JOA) score, and neck disability index (NDI) score were used to evaluate the improvement inclinical symptoms. The results of the difference in improvement from preoperatively to the final follow‐up assessment were assessed using a paired t‐test or Mann–Whitney U‐test.

Results

The LKA and GKA decreased from the preoperative average of 64.42 (range, 38–86) and 35.50 (range, 10–81) to an average of 16.83 (range, −2 to 46) and 4.25 (range, −22 to 39) postoperatively, respectively. The average correction rates of the LKA and GKA were 76.11% and 111.97%, respectively. All patients had achieved satisfactory relief of neurological symptoms (p < 0.01). JOA scores were improved from 10.42 (range, 8–16) preoperatively to 15.25 (range, 11–18) at final follow‐up (p < 0.01). NDI scores were decreased from an average of 23.25 (range, 16–34) preoperatively to an average of 7.08 (range, 3–15) at the final follow‐up (p < 0.01).

Conclusion

Anterior‐only correction and reconstruction is a safe and effective method for correcting cervical kyphosis in NF‐1 patients. In fixed cervical kyphosis cases, preoperative skull traction should also be considered.
Dispute Resolution in Real Estate Transactions: Examining Factors Determining the Selection of Strategies Used
Authors: Oluleye Ifeoluwa Benjamin , Oyetunji Abiodun Kolawole , Ogunleye Mukaila Bamidele
Published: May 2024

Disputes are inevitable in human interaction during business transactions. There are growing numbers of reported cases associated with disputes in real estate. Disputants always seek for ways to resolve and manage the varying issues arising from these transactions. This study examined the choice of dispute resolution strategies and the factors influencing its adoption in real estate in the bid to provide information capable of promoting peaceful co-existence amongst disputant parties. Structured questionnaires were administered to 60 disputants and 24 real estate firms in Akure, Nigeria and the information collected were analysed using the Mean Item Score (MIS). Findings showed that arbitration, litigation, Ijoko Ojogbon (a weekly TV-series program on land dispute settlement) and palace court are the top three most adopted strategies for real estate dispute resolution in the study location. Litigation, as found out, is being sought when ADR fails to pacify the issue at hand. The traditional strategies of dispute resolution such as Ijoko-Ojogbon and palace court were more prominent among the disputant because the time involved, the verdict enforcement and the cost in obtaining a judgement are relatively cheaper and are adduced as the major factors determining the choice of resolution strategy adopted by the disputants. It is therefore recommended that the crippling formalism and the unnecessary delay involved in litigation should be checked to hasten the resolution process. The traditional strategies of dispute resolution should be widely embraced, while the government at all levels should put up laws that will further empower traditional ADR process.
Assessment of the Triggers of Inefficient Materials Management Practices by Construction SMEs in Nigeria
Authors: Eze Chidiebere Emmanuel , Awodele Imoleayo Abraham , Adegboyega Adesoji Anthony , Onyeagam Onyealilam Peter , Guto Jibrin Ahmed
Published: May 2024

Inefficient material management throughout the construction projects value chain has resulted to poor performance especially in terms of time, cost, quality, and productivity. Even well-organised large construction organisations still fall prey to this project performance killer; as adequate attention is not given to material management as a necessary key project management function. Thus, this study assessed the factors that trigger inefficient material management practices by construction SMEs in Port Harcourt, Nigeria. The study utilised a quantitative survey method and convenience sampling technique in the distribution of the structured questionnaire used to gather data from project managers, procurement officers and construction professionals working with the construction SMEs. With a 93.33% response rate, the gathered data were analysed using percentage, frequencies and factor analysis with principal component analysis. It was found that the major triggers of inefficient materials management among construction SMEs are; traditional approach and maintenance issues, manufacturer error and poor planning, inventory management issues, poor handling of procurement, materials estimating problems, storage problems and insecurity, and communication issues. It was concluded that the predominance of these triggers in the management of materials among construction SMEs would result in a continued poor performance of construction projects, especially with regards to project time, cost, quality and productivity. The study recommends a move away from the traditional methods of managing materials and the adoption of a technological-based material management system.
Business Continuity Planning for Condominium Managing Agents in Sri Lanka: Resilience during Pandemics
Authors: Peiris Sanduni , De Silva Nayanthara
Published: May 2024

Business Continuity (BC) of condominiums is being greatly affected by the COVID-19 pandemic. The pandemic is highly contagious, imposing a huge risk on community-based environments in which residents share different common facilities such as lifts, recreational areas, swimming pools, gyms. Besides, the apartments are mostly used as closed units without a solid connection with the environment. Such settings may heavily contribute in spreading any contagious disease, justifying the strict care extremely demanded at residentials. As the caretaker, the Facilities Management (FM) service provider, also known as the Managing Agent (MA) must continue its operations while facing the pandemic with a huge risk. Rather than being reactive towards the emerging struggles, it is more effective to have a proactive approach in combatting a pandemic. Business Continuity Planning (BCP) allows an organisation to be equipped with all mandatory plans and strategies which can be implemented before the pandemic strikes. Hence, this paper proposes a Pandemic BCP model for MAs which can be utilized for the on-going COVID-19 and future pandemics. Data were gathered using literature, expert interviews, site observations and document review. It was observed that none of the organisations had BC plans prepared for a pandemic. However, most experts admitted the importance of BCP in this context. They mentioned that the remote working culture already established in MAs, heavily contributed in adapting to the situation. Further, satisfactory accommodation facilities provided for the on-site staff was witnessed during the site observations. The documents review revealed the comprehensiveness of prompt action taken by MAs to resume operation of the critical functions. The proposed model consists of six stages and the paper discusses the factors to be considered under each stage of the model. MAs can utilize this plan effectively in adapting to the current and future pandemics to ensure solid BC.
Urban Informality and COVID-19 Responses in Masvingo City, Zimbabwe: Questioning City Inclusivity
Authors: Chigwenya Average , Chigara Benviolent , Simbanegavi Prisca
Published: May 2024

In many cities, urban informality is sidelined in the provision of services and development of the city. The outbreak of COVID-19 has called for myriad interventions to stop the spread in many cities. The big question in the city of Masvingo is how urban informality has been included in these interventions. COVID-19 has been on the increase since it was ever recorded in the city of Masvingo. As at end of August 2020, over 200 cases of COVID-19 have been recorded and pointers also show that cases are on the increase. Many people have been deprived of their livelihoods in the city due to the outbreak of COVID-19, thereby exposing people to vulnerability due to lack of livelihoods. The outbreak of COVID-19 has also resulted in closure of countless economic activities in the city, thereby depriving people from their sources of livelihoods. The most affected by the closure of economic activities are the informal traders. The outbreak of COVID-19 pandemic has called for copious interventions to try and stop the spread of the disease. The study examined the inclusivity of COVID-19 interventions in the city of Masvingo to see how they include other disadvantaged groups such as the urban informality. The informal sector in the city of Masvingo is not included in the city’s COVID-19 response strategies. The city is mainly focusing on the formal sector in their response strategies, thereby leaving the informal sector out and exposing them to elevated risk of contracting the COVID-19 disease. This research examined the inclusivity of the COVID-19 interventions in the city of Masvingo, with special reference to the people in the informal sector. The informal sector, even though they live in cities, they are usually regarded as people living in the urban periphery because they are not included in the city’s development agenda and service delivery system. The research applied a qualitative methodology where in-depth interviews and field observations were used to collect data. Interviews were done with city authorities and people in the informal sector. The research showed that the interventions taken to fight the outbreak of the COVID-19 have not benefited the people in the informal sector but only the formal sector. The informal sector has been sidelined, showing a clear exclusionary urban policy. Their livelihoods were destroyed in the guise of preventing the spread of the COVID-19 pandemic. However, such destructions were not done in the formal sector which again apparently shows exclusive urban policy. The research therefore calls for a more holistic approach in the fight against COVID-19 disease for the inclusive of the city and the betterment of life for all people in the city.
Subjective and Objective Monitoring Markers: Are They Related to Game Performance Indicators in Elite Female Volleyball Players?
Authors: Rebelo André , Martinho Diogo V. , Pires Inês G. , Arrais Inês , Lima Ricardo , Valente-dos-Santos João , Pereira João R.
Published: May 2024

Purpose: This cohort study aimed to investigate the relationship between subjective (wellness and internal training load [ITL]) and objective (neuromuscular fatigue) monitoring markers and performance aspects (reception quality [RQ] and attack efficiency [AE]) in professional female volleyball players. Methods: The study was conducted over an 8-week period during the final mesocycle of the competitive phase. A total of 24 training sessions and 10 matches were included in the analysis. Subjective measures of wellness and ITL were assessed, and neuromuscular fatigue was evaluated using countermovement-jump (CMJ) height. RQ and AE were determined based on game statistics. Results: The study found a positive relationship between wellness and RQ, particularly affecting outside hitters and liberos. ITL showed a positive association with AE, primarily impacting outside hitters, opposite hitters, and middle blockers. Additionally, ITL demonstrated a negative correlation with RQ, mainly affecting outside hitters and liberos. CMJ performance was associated with AE, where a decrease in CMJ height was linked to reduced AE. Conclusions: The findings highlight the importance of considering players’ wellness scores in training and match strategies for different positions. Careful management of training loads, considering both physical and technical demands, is crucial for optimizing performance outcomes. Monitoring neuromuscular fatigue, as indicated by CMJ performance, is particularly relevant for outside hitters, opposite hitters, and middle blockers involved in attack actions. Coaches, trainers, and sports practitioners can use these insights to develop position-specific training protocols and implement effective strategies for maintaining or improving performance metrics under various stressors.
Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy
Authors: Komatsu Toshiaki , Kawai Yuka , Takayama Yoko , Akamada Yuto , Kusume Eri , Ikeda Masaomi , Tsumura Hideyasu , Ishii Daisuke , Iwamura Masatsugu , Okamoto Hirotsugu , Hanaki Hideaki , Otori Katsuya
Published: May 2024

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC
90
, 0.5 mg/L, and MIC
50
, and 1.0 mg/L, to account for methicillin-susceptible
Staphylococcus aureus
(MSSA) or
Escherichia coli
. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC
50
for
E. coli
or MIC
90
for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.
Cryptic environmental conjugative plasmid recruits a novel hybrid transposon resulting in a new plasmid with higher dispersion potential
Authors: Muñoz-Gutiérrez Iván , Cantu Luis , Shanahan Jack , Girguis Miray , de la Cruz Marlene , Mota-Bravo Luis
Published: May 2024

Cryptic conjugative plasmids lack antibiotic-resistance genes (ARGs). These plasmids can capture ARGs from the vast pool of the environmental metagenome, but the mechanism to recruit ARGs remains to be elucidated. To investigate the recruitment of ARGs by a cryptic plasmid, we sequenced and conducted mating experiments with
Escherichia coli
SW4848 (collected from a lake) that has a cryptic IncX (IncX4) plasmid and an IncF (IncFII/IncFIIB) plasmid with five genes that confer resistance to aminoglycosides (
strA
and
strB
), sulfonamides (
sul2
), tetracycline [
tet
(
A
)], and trimethoprim (
dfrA5
). In a conjugation experiment, a novel hybrid Tn21/Tn1721 transposon of 22,570 bp (designated Tn7714) carrying the five ARG mobilized spontaneously from the IncF plasmid to the cryptic IncX plasmid. The IncF plasmid was found to be conjugative when it was electroporated into
E. coli
DH10B (without the IncX plasmid). Two parallel conjugations with the IncF and the new IncX (carrying the novel Tn7714 transposon) plasmids in two separate
E. coli
DH10B as donors and
E. coli
J53 as the recipient revealed that the conjugation rate of the new IncX plasmid (with the novel Tn7714 transposon and five ARGs) is more than two orders of magnitude larger than the IncF plasmid. For the first time, this study shows experimental evidence that cryptic environmental plasmids can capture and transfer transposons with ARGs to other bacteria, creating novel multidrug-resistant conjugative plasmids with higher dispersion potential.

IMPORTANCE

Cryptic conjugative plasmids are extrachromosomal DNA molecules without antibiotic-resistance genes (ARGs). Environmental bacteria carrying cryptic plasmids with a high conjugation rate threaten public health because they can capture clinically relevant ARGs and rapidly spread them to pathogenic bacteria. However, the mechanism to recruit ARG by cryptic conjugative plasmids in environmental bacteria has not been observed experimentally. Here, we document the first translocation of a transposon with multiple clinically relevant ARGs to a cryptic environmental conjugative plasmid. The new multidrug-resistant conjugative plasmid has a conjugation rate that is two orders of magnitude higher than the original plasmid that carries the ARG (i.e., the new plasmid from the environment can spread ARG more than two orders of magnitude faster). Our work illustrates the importance of studying the mobilization of ARGs in environmental bacteria. It sheds light on how cryptic conjugative plasmids recruit ARGs, a phenomenon at the root of the antibiotic crisis.
Human plasma-like medium (HPLM) induces
Cryptococcus neoformans in vivo
cell morphologies
Authors: G. Mozo Eduardo , Ross Orlando , Yuecel Raif , Dambuza Ivy M. , Mukaremera Liliane
Published: May 2024

The fungal pathogen
Cryptococcus neoformans (C. neoformans
) forms yeast cells of different sizes and morphological characteristics during infection. These features are usually not seen in standard laboratory
in vitro
conditions. Here, we describe
in vivo
cell morphologies when
C. neoformans
is grown in human plasma-like medium at 37°C, 5% CO
2
. We observed mixed-size populations of cells less than 1 µm up to 16.8 µm in cell diameter, increased capsule size, high chitin, and DNA content in larger cells. Our findings show that serum is not required for human plasma-like medium (HPLM)-induced
C. neoformans
cellular heterogeneity. Thus, this new method offers an opportunity to investigate factors of
C. neoformans
that mediate pathogenesis or host–pathogen interactions in a physiologically relevant setting.

IMPORTANCE

We provide a description of new
in vitro
culture condition using the human plasma-like medium that supports the formation of the full range of
in vivo
cell morphologies of
C. neoformans
.
Evaluating a novel online behavioural intervention to encourage cost-conscious strategies among US adults with chronic conditions who are enrolled in a high-deductible health plan: a proof-of-concept pilot study
Authors: Peirce Alexandra , Lin Ying-Jen , Fagerlin Angela , Heisler Michele , Levy Helen , Kullgren Jeffrey
Published: May 2024

Objectives

Patients with chronic conditions enrolled in high-deductible health plans (HDHPs) face cost-related access barriers and high out-of-pocket spending. Our objectives were to develop a novel behavioural intervention to help HDHP enrollees with chronic conditions use cost-conscious strategies and evaluate the intervention’s preliminary effectiveness, acceptability and feasibility.

Design

Prospective.

Setting

Online (USA).

Participants

36 US adults enrolled in an HDHP through their employer or an exchange with diabetes, hypertension, asthma, coronary artery disease and/or chronic obstructive pulmonary disease. 31/36 participants completed the study.

Intervention

We developed a 5-week intervention consisting of a website with educational modules on discussing costs with clinicians, saving for future healthcare costs, comparing healthcare prices and quality, preparing for appointments, following up after appointments and planning for future healthcare needs; and emails encouraging participants to access each module.

Outcomes

We conducted a single-arm proof-of-concept pilot study of the intervention. Baseline and postintervention surveys measured primary outcomes of health insurance literacy and confidence in using cost-conscious strategies. 10 participants completed postintervention interviews.

Results

31 (86%) participants completed a baseline and postintervention survey. Mean health insurance literacy scores (20–80 scale) improved from 56.5 to 67.1 (p<0.001). Mean confidence scores (0–10 scale) improved for talking to a healthcare provider about cost (6.1–7.6, p=0.0094), saving for healthcare (5.8–6.6, p=0.068), comparing prices (5.4–6.9, p=0.005) and comparing quality (6.1 to 7.6, p=0.0034). Participants found the website easy to use and helpful for learning about cost-conscious strategies on postintervention interviews.

Conclusions

Our novel behavioural intervention was acceptable to HDHP enrollees with chronic conditions, feasible to deliver and associated with increased health insurance literacy and confidence in using cost-conscious strategies. This intervention should be tested in a definitive randomised controlled trial that is fully powered to evaluate its effects on cost-related access barriers, out-of-pocket spending and health outcomes in this growing patient population.
Protocol for a pragmatic randomised controlled feasibility study ofMS WorkSmart: an online intervention for Australians with MS who are employed
Authors: van der Mei Ingrid , Thomas Sarah , Shapland Sue , Laslett Laura L , Taylor Bruce V , Huglo Alisée , Honan Cynthia
Published: May 2024

Introduction

Multiple sclerosis (MS) causes a wide variety of symptoms. Loss of income due to sickness and early retirement comprise one-third of the total cost of MS in Australia. An intervention that maximises work productivity and keeps people with MS in the workforce for longer could provide a large societal cost saving and improve quality of life. The aim is to test the feasibility of delivering and evaluating a 10-week digitally delivered intervention called ‘MS WorkSmart’. Findings will provide insights into participant profiles and address key methodological and procedural uncertainties (recruitment, retention, intervention adherence and engagement, and selection of primary outcome) in preparation for a subsequent definitive trial.

Methods and analysis

A parallel-arm randomised controlled feasibility study, comparing those randomised to receive the MS WorkSmart package plus usual care (n=20) to those receiving usual care only (n=20). Australians with MS, aged 18–60 years, who are employed, and self-report work instability will be recruited from the Australian MS Longitudinal Study. Online surveys, at baseline and 1-month postintervention, will include MS-related work productivity loss and risk of job loss, MS work behaviour self-efficacy, health-related quality of life, fatigue severity, MS symptom impact on work, intention to retire due to MS, MS-related work difficulties, and awareness and readiness for change at work. Qualitative feedback will be obtained via a semistructured survey following the intervention (for participants) and via interviews (coaches). Analyses will be primarily descriptive and focus on the feasibility and acceptability of the intervention and study procedures. Progression criteria will guide decisions around whether to progress to a full trial.

Ethics and dissemination

The study has been approved by the University of Tasmania Human Research Ethics Committee (H0024544). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and community presentations.

Trial registration number

ACTRN12622000826741.
Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India
Authors: Mukherjee Ankita , Yatirajula Sandhya Kanaka , Kallakuri Sudha , Paslawar Srilatha , Lempp Heidi , Raman Usha , Kumar Ashok , Essue Beverley M , Sagar Rajesh , Singh Renu , Peiris David , Norton Robyn , Thornicroft Graham , Maulik Pallab Kumar
Published: May 2024

Introduction

There are around 250 million adolescents (10–19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents’ Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation.

Methods

Case study method will be used and the data will include a mix of quantitative metrics and qualitative data. The UK Medical Research Council’s guidance on evaluating complex interventions, the Reach, Efficacy, Adoption, Implementation and Maintenance Framework and the Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Safety/Side Effects and, Equity criteria will be used to develop a conceptual framework and a priori codes for qualitative data analysis. Quantitative data will be analysed using descriptive statistics. Implementation fidelity will also be measured.

Discussion

The process evaluation will provide an understanding of outcomes and causal mechanisms that influenced any change in trial outcomes.

Ethics and dissemination

Ethics Committee of the George Institute for Global Health India (project number 17/2020) and the Research Governance and Integrity Team, Imperial College, London (ICREC reference number: 22IC7718) have provided ethics approval. The Health Ministry’s Screening Committee has approved to the study (ID 2020-9770).

Trial registration number

CTRI/2022/02/040307.
Who dies from venous thromboembolism after hospitalisation for other reasons in England?: a national retrospective cohort study
Authors: Healey Frances , Gower Janine , Roberts Lara , Arya Roopen , Beresford Matthew , Fowler Aidan , Kirkpatrick Graeme , Oldfield Ethel , Weaver Rachel
Published: May 2024

Objectives

Venous thromboembolism (VTE) is a major cause of morbidity and mortality globally, with hospital-associated thrombosis (HAT) accounting for at least half of VTE. We set out to understand more about deaths from HAT in England, to focus improvement efforts where they are needed most.

Design

A retrospective cohort combining death certification and hospital activity data to identify people with an inpatient or day case hospitalisation where no VTE diagnosis was recorded, and who died from VTE in a hospital or within 90 days of discharge, between April 2017 and March 2020.

Setting

All deaths occurring in England and all National Health Service-funded hospital care in England.

Participants

After 0.1% of cases were excluded due to duplicate but conflicting records, a cohort of 13 995 deaths remained; 54% were women, and 26% were aged under 70 years.

Outcome measures

Analysis of age, gender, primary diagnosis, type of admission, specialties and (for day cases) procedure types were preplanned.

Results

Only 5% of these deaths followed planned inpatient admissions. Day case admissions preceded 7% of VTE deaths. Emergency inpatient admissions, medical specialties and infection-related primary diagnoses predominated in people who died from VTE after hospitalisation where no VTE diagnosis was recorded. Most deaths occurred in a hospital or within 30 days of discharge.

Conclusions

International efforts to reduce HAT historically focused on planned inpatient admissions. Further initiatives and research to prevent deaths from VTE after hospitalisation should focus on the emergency care pathway where most deaths occurred, with people undergoing day case procedures an important additional focus.
Documentary analysis of national and international guidance for community clinicians referring patients with suspected chronic limb-threatening ischaemia
Authors: Atkins Eleanor , Birmpili Panagiota , Kellar Ian , Glidewell Liz , Cromwell David A
Published: May 2024

Background

Delayed referral of patients with chronic limb-threatening ischaemia (CLTI) from the community to vascular services may increase risk of amputation due to delayed revascularisation. Lack of appropriate guidance for clinicians in the community may contribute to this problem. This documentary analysis investigated referral guidance available to primary care clinicians.

Methods

National and international documents providing guidance on CLTI management were identified by searching sources including Medline, Embase, Guidelines International Network and College/Society websites. Data were extracted on referral recommendations, target audience and author groups. Recommendations were coded according to the Behaviour Change Technique Taxonomy. Clinical practice guideline quality and ease of implementation were assessed independently by two reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) II and Guideline Implementability Appraisal (GLIA) tools, respectively.

Results

12 documents containing guidance on CLTI referrals were included. Five were clinical practice guidelines. Nine targeted clinicians in the community among their audience, yet only one included a primary care clinician in their author group. Recommendations on identification and referral of CLTI were often in non-specific language and frequently assumed specialist knowledge of vascular disease. Just 4 of the 93 behaviour change techniques were identified in the guidance documents. Three relevant domains of the AGREE II tool were scored for five clinical practice guidelines: stakeholder involvement (range 21.4%–52.4%, mean 42.9%), clarity of presentation (range 71.4%–92.9%, mean 82.9%) and applicability (25.0%–57.1%, mean 36.8%). The GLIA tool identified barriers to ease of implementation for all five clinical practice guidelines.

Conclusions

Most guidance for clinicians in the community on the management of CLTI has been written without their input and assumes knowledge of vascular disease, which may be lacking. Future guidance development should involve community clinicians, consider using additional behaviour change techniques, and improve the applicability and ease of implementation of recommendations.