bluuebunny/crossref_metadata_2025 huggingface dataset:
WTO Law and Jurisprudence on Invasive Alien Species in the Global South
Authors: EJ Mogomotsi Goemeone , Mogomotsi Patricia K , O Moeti Onthatile
Published: July 2022

International trade is a significant factor in the introduction of invasive alien species around the world. The preparedness of countries through their domestic regulations to combat invasive alien species differs from country to country. This article discusses the potential of WTO law in combating the spread of invasive alien species in countries with weak environmental regulation regimes such as Botswana. It recognises the possibility of invoking provisions of WTO agreements by member states to combat the introduction and spread of invasive alien species. It concludes that the use of WTO agreements by developing countries may be an immediate solution to address and combat biodiversity losses in the global south. The article recommends the building of technical and scientific capacity by developing countries to effectively use international trade law for environmental protection.
Uh and Um as Pragmatic Markers in Dialogues: A Contrastive Perspective on the Functions of Planners in Fiction and Conversation
Authors: Tonetti Tübben Ilenia , Landert Daniela
Published: July 2022

The planners uh and um fulfil a range of interpersonal and discursive functions, akin to other pragmatic markers. Although there appear to be differences between the planners’ functions across genres, the factors influencing these differences have not been analysed comprehensively so far. In our study, we analyse the frequency and functions of uh and um across three different genres: spontaneous conversation, scripted dialogues in television series and dialogues in improvised theatre. Our findings suggest that both the fictional nature of a text and its degree of composition have an influence on the planners’ functions. Our results confirm that planners are indeed pragmatic markers which serve a range of textual and interpersonal functions, and that the frequency and functions of planners are affected by factors relating to the context of language production, which include spontaneity as well as the content and function of a text.
Shared Responsibilities in Fighting the Plague in Moldavia, 1800–1830
Authors: Grigoruță Sorin
Published: July 2022

The plague was the epidemic disease that had the deepest impact upon the lives and memories of the people who lived in Moldavia up to the mid-nineteenth century. By investigating a series of anti-epidemic measures, this paper aims to emphasise the shared responsibility for care during the plague epidemics. The tasks of coordinating and financing these anti-epidemic efforts were assumed by the reigning leaders. Their authority, in some situations, was substituted by representatives of the Russian military administration, at times when the Romanian Principalities were occupied by Russian troops. The anti-epidemic mobilization gathered all available forces to fight the spread of disease: amongst others, the boyars, merchants, and local authorities. The physicians of the times represented a discrete, but sometimes, an essential presence. More numerous but scarcely involved in the 1828–1830 epidemic period, doctors played a decisive role especially in the context of the medical-administrative transformations after 1830. The role of the Church should also be noted, as priests had the task of popularizing the anti-epidemic measures within their communities and of persuading their congregations to accept public health measures.
The ‘Greenlandization’ of Care: Disability in Postcolonial Greenland, 1950s–1980s
Authors: Derksen Anna
Published: July 2022

When the former Danish colony Greenland obtained Home Rule in 1979, becoming an autonomous region within the Danish Realm, it faced the challenge of having to establish a comprehensive social welfare system. This article looks at disability care and its interrelations with post-colonialism and national identity formation, as previous practices of medical care and accommodation in Danish institutions were replaced with local solutions. Frame analysis reveals the outlines of the responsibilities of Danish experts for disabled Greenlanders under colonial rule and during the modernization period until 1979. The transition phase of the early 1980s was a central arena for Greenlandic national discourse wherein care responsibilities in welfare policies, disability care institutions, advocacy organizations and the media were framed and renegotiated. The ‘Greenlandization’ of disability care and the respective shift in responsibilities was a highly uneven process that continued to be suffused with Danish norms and practices.
Impact of Advection Schemes on Tracer Interrelationships in Large-Eddy Simulations of Deep Convection
Authors: Hernández Pardo Lianet , Morrison Hugh , Lauritzen Peter H. , Pöhlker Mira
Published: July 2022

This study investigates the preservation of tracer interrelationships during advection in large-eddy simulations of an idealized deep convective cloud, which is particularly relevant to chemistry, aerosol, and cloud microphysics models. Employing the Cloud Model 1, advection is represented using third-, fifth-, and seventh-order weighted essentially non-oscillatory schemes. As a simplified analogy for cloud hydrometeors and aerosols, several inert passive tracers following linear and nonlinear relationships are initialized after the cloud reaches ∼6-km depth. Numerical mixing in the simulated turbulent convective clouds leads to significant deviations from the initial nonlinear relationships between tracers. In these simulations, a considerable fraction of the grid points where the tracers’ nonlinear relationships are altered from advection are classified as unrealistic (e.g., ∼13% for the environmental tracers on average), including errors from range-preserving unmixing and overshooting. Errors in the sum of three tracers are also relatively large, ranging between ∼1% and 16% for 5% of the grid points in and near the cloud. The magnitude of unrealistic mixing and errors in the sum of three tracers generally increase with the order of accuracy of the advection scheme. These results are consistent across model grid spacings ranging from 50 to 200 m, and across three different flow realizations for each combination of grid spacing and advection scheme tested. Tests employing a previously proposed scalar normalization procedure show substantially reduced errors in the sum of three tracers with a relatively small negative impact on other tracer relationships. This analysis, therefore, suggests efficacy of the normalization procedure when applied to turbulent three-dimensional cloud simulations.

Significance Statement

In nature, transporting several quantities through bulk motions of a fluid does not affect preexisting relationships between them. However, this is not always accomplished in numerical models of the atmosphere, because of intrinsic limitations in the transport algorithms employed. We aim to investigate how these errors behave in 3D realistic simulations of a cumulus cloud, where the turbulent flow constitutes a particular challenge. We show that relationships between quantities are significantly and frequently perturbed during bulk transport in the model. Moreover, our results suggest that increasing complexity of the bulk-transport algorithms (in a way that is conventionally employed for improving the representation of individual quantities) tends to worsen the representation of relationships between two or three quantities.
Innovation Imprinting: Why Some Firms Beat the Post-IPO Innovation Slump
Authors: Wies Simone , Moorman Christine , Chandy Rajesh K.
Published: July 2022

Growth and innovation are primary arguments for firms that aim to go public and access resources from the stock market. So it is ironic that going public is, for a majority of firms, associated with a pronounced slump in breakthrough innovation. This article proposes an actionable, marketing-related explanation for why some firms that go public manage to beat the post–initial public offering (IPO) innovation slump: innovation imprinting. The authors argue and demonstrate that firms that engage in innovation imprinting before going public attract a segment of concordant investors whose risk preferences are more supportive of breakthrough innovation than investors at large. These investors, in turn, reward the firms’ continued introduction of breakthrough innovations after they have gone public. By analyzing the innovation patterns of 207 firms in the consumer packaged goods sector before and after an IPO, the authors observe that one-third of firms are able to maintain or beat their pre-IPO levels of breakthrough innovations after going public. By studying their actions, the investors they attract, and their financial performance and survival rates, the authors provide empirical evidence for the importance of innovation imprinting and concordant investors in helping firms beat the post-IPO innovation slump.
3T external phased-array magnetic resonance imaging in detection of obstetric anal sphincter lesions: a pilot study
Authors: Pinta Tarja , Ruohonen Jyrki , Kallio-Packalen Marja , Zhabin Ivan , Kirss Jaan
Published: July 2022

Background

Three-dimensional endoanal ultrasound (3D EAUS) has been the gold standard for detecting anal sphincter lesions in patients with a history of obstetric anal sphincter injury (OASI). Advances in imaging technologies have facilitated the detection of these lesions with external phased-array magnetic resonance imaging (MRI), which could offer an alternative imaging modality for the diagnosis of residual OASI (ROASI) in centers where 3D EAUS imaging is not available.

Purpose

To compare two diagnostic modalities: the 3D EAUS and 3T external phased-array MRI in the detection of residual anal sphincter lesions.

Material and Methods

A total of 24 women with a history of OASI were imaged with both 3D EAUS and 3T external phased-array MRI after primary repair of the injury. Intraclass correlation (ICC) and interrater reliability (IRR) values were calculated for the grade and circumference of the sphincter lesion. Sphincter lesions were graded according to the Sultan classification.

Results

There was an almost perfect agreement between 3D EAUS and 3T external phased-array MRI in determining the extent of the sphincter lesions according to the Sultan classification (κ = 0.881; P < 0.001) and the circumference of the external anal sphincter defects, measured in degrees (κ = 0.896; P < 0.001).

Conclusion

The results of this study indicate that 3T external phased-array MRI and 3D EAUS yield comparable results in the diagnosis of ROASI. These findings suggest that 3T external phased-array MRI could serve as an alternative diagnostic modality to 3D EAUS in the diagnosis of ROASI.
Influence of forging action on the microstructural and mechanical characteristics of the friction stir welded joints of aluminum alloy with varied joint configurations
Authors: Thakur Ankit , Ojha Ambikashwer , Bhadauria Shailendra Singh , Sharma Varun
Published: July 2022

The variation in the forging action during single-side friction stir welding (SS-FSW) and double side friction stir welding (DS-FSW) joining of AA-6061 T6 alloy by friction stir welding (FSW) process was conducted. The microscopic study of the stir zone (SZ) of SS-FSW joint configurations showed that the forging action obtained with a 3° tool tilt angle (TTA) provided better intermixing of material, with significant downward and inclined flow of plasticized material under the shoulder interaction zones. This led to the maximum grain refinement as compared to the forging action obtained with 0° and 2° TTA. For DS-FSW joint, a good interlocking between the material stirred during the first and second pass was observed, which led to maximum joint efficiency, and the elimination of the problem of insufficient root penetration observed during the SS-FSW. The misorientation analysis revealed that the percentage of high angle grain boundaries (HAGBs) significantly increased for DS-FSW joint due to the small thermal gradient along the plate thickness. Moreover, the dominance of B/[Formula: see text] shear texture with sufficient dissimilarity in the crystallographic orientation to the random texture was observed within the SZ of DS-FSW joint.
Assessing the Business Ecosystem for Indian SMEs: A Resource-Based View
Authors: Mittal Ruhee , Soriya Sushila , Prakash Bishwajeet , Lochab Anshu
Published: July 2022

The purpose of this study is to develop a MSME business facilitator index (MSME-BFI) to investigate the major factors which lead to the growth and development of MSMEs in the top performing and poor performing states of India. The data for various parameter for estimating the index such as infrastructure (road and electricity), human resources (labour participation rate and literacy rate), information communication uses (computer and internet), fiscal discipline and other economic indicators is collected from different government surveys and reports. The study revealed that states should focus on labour force, infrastructure, ICT technology, credit facilities, financial management and economic governance for the growth of MSME’s. There exist major disparities in the performance of the MSMEs, when divided into top performing and poor performing states, respectively. The research helps policymakers and government to focus on the leading barriers/factors which lagged the states to achieve the higher economic development.
Reflective writing in a community music project with students in higher music education
Authors: Kruse-Weber Silke , Schiavio Andrea , Kirchgäßner Erik M , Bucura Elizabeth
Published: July 2022

Meet4Music (M4M) is a low-threshold community music program based at the University of Music and Performing Arts Graz, Austria, offering free participatory sessions to people from all social and cultural backgrounds, including students. The program allows attendees to experience an emerging field of music pedagogy and approach current challenges of migration and cultural diversity from an artistic perspective. The purpose of this study was to explore how students considered and reflected on their M4M experiences. Research questions included the following: (1) How did students consider the experience of making music in a heterogeneous ensemble, and what meanings might they have made from it? And, (2) What aspects of M4M may have contributed to artistic and interpersonal enrichment, and in what ways? We examined meanings developed across the various practices involved in this artistic initiative, with a specific focus on the students’ experiences. To do so, qualitative data based on their written reflections are presented, analyzed, and discussed. Findings include attributions for M4M and personal impact. Themes center on a holistic understanding of the musical community of the program and students’ reflexive and responsive attitudes. Implications include refining notions of artistic citizenship and recommendations for higher music education.
Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple sclerosis
Authors: Ladakis Dimitrios C , Yao Pamela J , Vreones Michael , Blommer Joseph , Kalaitzidis Grigorios , Sotirchos Elias S , Fitzgerald Kathryn C , Saidha Shiv , Calabresi Peter A , Kapogiannis Dimitrios , Bhargava Pavan
Published: July 2022

Background:

Mitochondrial dysfunction plays an important role in multiple sclerosis (MS) disease progression. Plasma extracellular vesicles are a potential source of novel biomarkers in MS, and some of these are derived from mitochondria and contain functional mitochondrial components.

Objective:

To evaluate the relationship between levels of mitochondrial complex IV and V activity in neuronally enriched extracellular vesicles (NEVs) and brain and retinal atrophy as assessed using serial magnetic resonance imaging (MRI) and optical coherence tomography (OCT).

Methods:

Our cohort consisted of 48 people with MS. NEVs were immunocaptured from plasma and mitochondrial complex IV and V activity levels were measured. Subjects underwent OCT every 6 months and brain MRI annually. The associations between baseline mitochondrial complex IV and V activities and brain substructure and retinal thickness changes were estimated utilizing linear mixed-effects models.

Results:

We found that higher mitochondrial complex IV activity and lower mitochondrial complex V activity levels were significantly associated with faster whole-brain volume atrophy. Similar results were found with other brain substructures and retinal layer atrophy.

Conclusion:

Our results suggest that mitochondrial measures in circulating NEVs could serve as potential biomarkers of disease progression and provide the rationale for larger follow-up longitudinal studies.
Model-free adaptive sliding mode control for intelligent vehicle longitudinal dynamics
Authors: Zhang-qi Feng , Hao-bin Jiang , Qi-zhi Wei , Yang-ke Hong , Abiodun Oluwaleke Ojo
Published: July 2022

Vehicle longitudinal dynamics system has the characteristics of being strongly non-linear, time-varying, and multiple-perturbed, so, it is difficult to build the mathematical model accurately. The control algorithms, based on accurate mathematical model, can hardly achieve the ideal effect, but control methods, which merely adopt input/output data (I/O) of a system, provides a solution. In this paper, by means of combing model-free adaptive control (MFAC) and sliding-mode control (SMC), the model-free adaptive sliding mode control (MFASMC) method is proposed. By comparison with feedback-feedforward control method, the MFASMC method can better improve the control effect and anti-disturbance performance. Meanwhile, the stability of MFASMC method was proven mathematically. Besides, the parameters of MFASMC method were optimized using genetic algorithm. Results of simulation and HiL test shows that the MFASMC method has fast response, strong robustness and smooth output. It would be better to apply it to the longitudinal dynamics control of intelligent vehicles.
Personality disorders and outcome after multidisciplinary pain therapy
Authors: Heyn Jens , Uenze Birgit , Christoph Ricarda , Baumann Nanette , Kiesewetter Isabel , Mihatsch Lorenz , Luchting Benjamin
Published: July 2022

Objectives

Interdisciplinary treatment programmes are the gold standard for patients suffering from chronic pain. However, several patient-related factors seem to influence the patients’ outcome. The aim of our study was to inquire whether patients with personality disorders (PD) might benefit less from an interdisciplinary treatment programme compared to patients without PD.

Methods

A prospective, observational study with chronic pain patients attending a 5-week interdisciplinary treatment programme was performed. Main outcome parameters were psychological stabilization and pain intensity before and after the programme.

Results

Out of the 104 included patients, 71 (68.3%) showed personality accentuations and 16 (15.4%) were diagnosed with PDs. PDs were mostly classified as histrionic, followed by borderline and narcistic personality. Patients diagnosed with histrionic accentuation showed a significantly better treatment response in terms of pain. Reduction in ADS (Allgemeine Depressionsskala – depression scale) was 3.4 in patients with PD and 11.1 in those without PD. Borderline patients showed a significant increase of ADS (by 2.0; p < 0.05) after programme completion.

Discussion

Patients with chronic pain and personality accentuations or disorder only showed a slightly different outcome after interdisciplinary treatment programme and should therefore not be excluded from these programmes. Registered at German Clinical Trials Register (DRKS-ID: DRKS00015141).
Illness conversations: Self-disclosure among children and youth with chronic illnesses
Authors: Pathmalingam Tharanni , Moola Fiona J , Woodgate Roberta L
Published: July 2022

Objective

Illness disclosure refers to when individuals with chronic illnesses make decisions to tell others about their disease. There is a lack of research on the complexity of disclosure among children and youth with chronic illnesses. We conducted a review of the literature to understand the process of disclosure among children and youth with chronic illnesses in the context of peer-based relationships.

Methods

A narrative review was completed using three databases. The search yielded 11 articles that utilized various research designs.

Results

Most of the literature was qualitative in nature. Most children and youth engaged in non-disclosure and concealment which is born out of fears of discrimination. Fewer children and youth engaged in unplanned disclosure, passive disclosure, partial disclosure, and open disclosure. Children and youth carefully consider who they are disclosing to and perceptions about other peoples’ responses strongly impact disclosure. Children and youth disclose verbally, behaviorally, and in written form. Disclosure is associated with both positive and negative effects, such as confidence, self-advocacy, and distress.

Discussion

Health providers and researchers should critically support disclosure and empower children and youth with the resources they need to be agents in their own disclosure decisions.
The impact of Inflammatory Bowel Disease related fatigue on Health-Related Quality of Life: a qualitative semi-structured interview study
Authors: Radford Shellie J , Moran Gordon W , Czuber-Dochan Wladyslawa
Published: July 2022

Background

Fatigue is a frequently reported symptom of Inflammatory Bowel Disease (IBD), having a negative impact on Health-Related Quality of Life (HRQoL). Patients’ experiences of this have not been researched in IBD.

Methods

Semi-structured interviews were conducted with adults with Crohn’s Disease from out-patient clinics in the United Kingdom. Interviews were audio-recorded and transcribed verbatim, then analysed using thematic analysis.

Results

Fourteen participant interviews were conducted. Three key themes were identified: 1) ‘The new normal’ established through adaptation and acceptance; 2) ‘Energy as a resource’ describing attempts to better manage fatigue through planning and prioritising tasks; 3) ‘Keeping healthy’ encompasses participants’ beliefs that ‘good health’ allows better management of fatigue.

Conclusion

Participants establish a ‘new’ normality, through maintaining the same or similar level of employment/education activities. However, this is often at the expense of social activities. Further research is required to explore patient led self-management interventions in IBD fatigue.
Exploring pregnant women’s experiences of stopping smoking with an incentive scheme with ‘enhanced’ support: a qualitative study
Authors: McCormack Fiona C , Hopley Rachel C , Boath Elizabeth H , Parry Sian L , Roscoe Suzie M , Stewart Antony , Birch Victoria A
Published: July 2022

Aim:

This study aims to understand pregnant women’s experiences of smoking cessation with an incentive scheme in a deprived UK city. This is important because smoking cessation with pregnant women is one of the most crucial public health initiatives to promote, and is particularly challenging in deprived areas. While financial incentive schemes are controversial, there is a need to better understand pregnant women’s experiences. The scheme combined quasi-financial incentives (shopping vouchers) for validated quits (carbon monoxide (CO) validated at < 10 ppm), enhanced support from smoking cessation advisors, the opportunity to identify a ‘Significant Other Supporter’ and nicotine replacement therapy.

Methods:

With the focus on understanding pregnant women’s experiences, a qualitative design was adopted. Semi-structured interviews were completed with 12 pregnant women from the scheme, and the three advisors. All interviews were transcribed, and thematic analysis conducted.

Results:

Pregnant women reported various challenges to quitting, including long-established routines, and stress. Participants were aware of stigma around incentives but were all very positive about the scheme. The relationship with advisors was described as fundamental. The women valued their advice and support, while uptake of the ‘Significant Other Supporter’ appeared low. Participants viewed the CO monitoring as ‘an incentive’, while the vouchers were framed as a ‘bonus’. Advisors perceived the vouchers as helping engage pregnant women and maintain quit status, and women appreciated the vouchers both as financial assistance and recognition of their accomplishments.

Conclusion:

This study highlights the great value women placed on the support, advice and monitoring from specialist advisors. The distinction between vouchers as a welcomed bonus, rather than ‘the incentive’ to engage, is important. How smoking cessation and schemes to promote this are communicated to pregnant women and health professionals is important, particularly given the stigma and controversy involved.
Back pain treatment: a new perspective
Authors: Steinmetz Anke
Published: July 2022

This article aims to provide new perspectives for the treatment of low back pain (LBP). A narrative literature review highlights the treatment strategies currently anchored in the guidelines as well as the extensive attempts to identify subgroups within the non-specific low back pain (NSLBP) classification. A variety of multimodal approaches exist for both diagnostic assessments and therapy approaches. Nonetheless, there are often gaps in the classification systems as well as in published treatment concepts with regard to the implementation of musculoskeletal functional disorders. Indeed, a growing body of evidence shows that more holistic and flexible approaches are needed to individually diagnose and target the complexity of LBP. As an example, both a diagnostic and a (independently developed) therapeutic LBP concept will be presented and discussed. Ultimately, guidelines and subgroup classification systems can only reflect the complexity of LBP, if they capture its entire multidimensional and biopsychosocial character in both the diagnostic and therapeutic processes. Furthermore, the expansion of the pain definition to include the nociplastic pain mechanism, as an important driver of LBP, has the potential to provide important impulses for further necessary research. In conclusion, the implementation of a functional musculoskeletal approach along with the emerging nociceptive pain concept in individually targeted holistic approaches seems to be the successful way to deal with the complexity of LBP.
Glycemic Variability Assessment in Newly Treated Exocrine Pancreatic Insufficiency With Type 1 Diabetes
Authors: Lewis Dana M. , Shahid Arsalan
Published: July 2022

Background:

Thirty-nine percent of people with type 1 diabetes may have lowered pancreatic elastase levels, correlated with exocrine pancreatic insufficiency (EPI or PEI). EPI is treated with oral supplementation of pancreatic enzymes. Little is known about the glycemic impact of pancreatic enzyme replacement therapy (PERT) in people with diabetes. This article demonstrates a method of assessing glycemic variability (GV), glycemic outcomes, and other changes in an individual with type 1 diabetes using open-source automated insulin delivery (AID).

Method:

Macronutrient, PERT intake, and EPI-related symptoms were self-tracked; diabetes data were collected automatically via an open-source AID system. Diabetes data were uploaded via Nightscout to Open Humans and downloaded for analysis alongside self-tracked data (food, PERT). Glycemic outcomes, macronutrients, PERT dosing, and a variety of GV metrics following meals were evaluated for one month before and one month after PERT commencement. Breakfast was assessed independently across both time periods.

Results:

In an n = 1 individual using an open-source AID, time in range was already above goal and improved further after PERT commencement. Glucose rate of change and excursions >180 mg/dL were reduced; mean high blood glucose index was reduced overall and more so specifically at breakfast following PERT commencement.

Conclusions:

GV can aid in assessing response to new-onset medications, as was demonstrated in this article for n = 1 individual with type 1 diabetes (using an open-source AID) after commencing PERT for newly identified EPI. GV may be useful for evaluating the efficacy of new-onset medications for people with insulin-requiring diabetes.
Phytochemical Characterization and Bioactivity Toward Breast Cancer Cells of Unhydrolyzed and Acid-Hydrolyzed Extracts of Fagonia indica
Authors: Miranda Cristobal L. , Kumbi Yadano , Wu Wenbin , Lee Hyi-Seung , Reed Ralph L. , Stevens Jan F.
Published: July 2022

Phytochemicals from the genus, Fagonia, have been attracting increasing attention due to their potential beneficial effects on human health. Fagonia species contain various types of phytochemicals such as flavonoids, alkaloids, saponins, terpenoids, coumarins and tannins. In this study, we investigated the phytochemical composition of unhydrolyzed and acid-hydrolyzed extracts of Fagonia indica and their bioactivity toward breast cancer MCF-7 cells in vitro. The results revealed that F. indica contains phytochemicals consistent with the reported phytochemical composition of this Fagonia species, with greater amounts of aglycones detected in the hydrolyzed extract. The crude extract of F. indica without acid hydrolysis was found to be ineffective in inhibiting the growth of MCF-7 cells at doses below 1000 µg/mL. However, after acid hydrolysis (to mimic gastro-intestinal hydrolysis), the F. indica extract became growth-inhibitory to MCF-7 cells as low as 10 µg/mL and the cytotoxicity increased with increasing dose and time of treatment. The results suggest that F. indica extracts contain phytochemicals in glycosidic forms whose aglycones are active as anti-proliferative agents toward breast cancer cells in vitro.
How much is too much? Pushing the limits of fluid removal via paracentesis
Authors: Al Khoury Rami
Published: July 2022

Peritoneal fluid accumulation can be caused by a multitude of factors. Patients with chronic cirrhosis can suffer from recurrent ascites requiring repeat paracentesis for fluid removal and symptom control. A paracentesis is a commonly performed procedure with a low risk profile that can be performed at the bedside by appropriately trained individuals. A large volume paracentesis is often therapeutic and focus should be placed on removing as much fluid as safely tolerated. We present a 57-year old Caucasian male with worsening abdominal distention and recurrent ascites who presented for progressive shortness of breath. Given the large volume of ascites noted, the patient underwent a passive bedside paracentesis with 29 L removed. The patient tolerated the 5-h procedure well without any post-procedure complications, challenging the extent of volume removal during bedside paracentesis.
A rare case of metastatic atypical meningioma that highlights the shortcomings of treatment options at present
Authors: Wrange Erik Kristian Maurice , Harders Stefan Markus Walbom
Published: July 2022

We report a case of a locally invasive recurrent atypical meningioma in the temporal region with late onset of meningioma lung metastasis. The patient was diagnosed in early adolescence with an atypical meningioma believed to be radiotherapy induced following treatment of a benign pilocytic astrocytoma in the hypothalamus region at 6 years of age. Even though the patient underwent several surgical and radiotherapy treatments, the intracranial meningioma kept growing and was locally invasive. The patient received experimental treatment with bevacizumab, a vascular endothelial growth factor A (VEGF-A)-inhibitor, for 4 years from age 26. Treatment was withdrawn after proven tumor growth on routine control MRI. A DOTA-TOC PET-CT-scan was performed to evaluate the DOTA-TOC somatostatin receptor number for possible SSTR (somatostatin receptor targeted therapy). In the included scan plan multiple lung metastasis were detected and later verified. Genomic tumor sequencing was performed, but no targeted treatment options were found. Instead, the patient finally, as the last treatment option, underwent 4 series of SSTR-targeted therapy (Lutetium DOTA-TOC). Unfortunately, the intracranial tumor component significantly progressed during the final stages of the treatment and the patient died less than a year after treatment was withdrawn at age 32. This case story illustrates the shortcomings of atypical/anaplastic meningioma treatment strategies at present and highlights the possibility of extracranial metastasis.
Human complete NFAT1 deficiency causes a triad of joint contractures, osteochondromas, and B-cell malignancy
Authors: Sharma Mehul , Fu Maggie P. , Lu Henry Y. , Sharma Ashish A. , Modi Bhavi P. , Michalski Christina , Lin Susan , Dalmann Joshua , Salman Areesha , Del Bel Kate L. , Waqas Meriam , Terry Jefferson , Setiadi Audi , Lavoie Pascal M. , Wasserman Wyeth W. , Mwenifumbo Jill , Kobor Michael S. , Lee Anna F. , Kuchenbauer Florian , Lehman Anna , Cheng Sylvia , Cooper Anthony , Patel Millan S. , Turvey Stuart E.
Published: July 2022

The discovery of humans with monogenic disorders has a rich history of generating new insights into biology. Here we report the first human identified with complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT1, encoded by NFATC2, mediates calcium-calcineurin signals that drive cell activation, proliferation, and survival. The patient is homozygous for a damaging germline NFATC2 variant (c.2023_2026delTACC; p.Tyr675Thrfs∗18) and presented with joint contractures, osteochondromas, and recurrent B-cell lymphoma. Absence of NFAT1 protein in chondrocytes caused enrichment in prosurvival and inflammatory genes. Systematic single-cell–omic analyses in PBMCs revealed an environment that promotes lymphomagenesis with accumulation of naïve B cells (enriched for oncogenic signatures MYC and JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further defines the detrimental effects associated with long-term use of calcineurin inhibitors.
Behçet’s disease presenting as neuroretinitis with pre-papillary vitreous infiltrate: a case report
Authors: Mahjoub Ahmed , Abdesslem Nadia Ben , Sellem Ilhem , Zaafrane Nesrine , Mahjoub Anis , Sakji Fatma , Ghorbel Mohamed , Mahjoub Hachemi , Yahia Wissal Ben , Guiga Ahmad
Published: July 2022

Objective

To report a case of Behçet’s disease (BD) presenting as a panuveitis with neuroretinitis and pre-papillary vitreous infiltrate.

Material and methods

A case report.

Results

A 43-year-old male presented with severely decreased vision in the left eye. Ophthalmological examination revealed unilateral non granulomatous panuveitis with occlusive retinal vasculitis, neuroretinitis and pre-papillary vitreous infiltrate. Initial swept source OCT revealed a “funnel-shaped” hyperreflective lesion overlying the optic disc corresponding to the pre-papillary vitreous infiltrate associated with optic disc edema and a serous retinal detachment extending to the macula. Examination by an internal medicine specialist revealed buccal aphthous ulcer and pseudofolliculitis lesions. BD diagnosis was made and the patient received corticosteroid and immunosuppressive therapy. The pre-papillary vitreous infiltrate resolution under treatment was documented with repeat swept source OCT.

Conclusion

Pre-papillary vitreous infiltrate has been rarely reported in the literature. This finding is a typical feature in severe cases of BD uveitis and is usually associated with a neuroretinitis. Optic disc OCT is useful to make the diagnosis and to monitor the resolution of the pre-papillary vitreous infiltrate.
Effectiveness and cost-effectiveness of an intervention to improve Initial Medication Adherence to treatments for cardiovascular diseases and diabetes in primary care: study protocol for a pragmatic cluster randomised controlled trial and economic model (the IMA-cRCT study)
Authors: Sánchez-Viñas Alba , Corral-Partearroyo Carmen , Gil-Girbau Montserrat , Peñarrubia-María M. Teresa , Gallardo-González Carmen , Olmos-Palenzuela María-del-Carmen , Aznar-Lou Ignacio , Serrano-Blanco Antoni , Rubio-Valera Maria
Published: July 2022

Background

Between 2 and 43% of patients who receive a new prescription in PC do not initiate their treatments. Non-initiation is associated with poorer clinical outcomes, more sick leave and higher costs to the healthcare system. Existing evidence suggests that shared decision-making positively impacts medication initiation. The IMA-cRCT assesses the effectiveness of the IMA intervention in improving adherence and clinical parameters compared to usual care in patients with a new treatment for cardiovascular disease and diabetes prescribed in PC, and its cost-effectiveness, through a cRCT and economic modelling.

Methods

The IMA intervention is a shared decision-making intervention based on the Theoretical Model of Non-initiation. A cRCT will be conducted in 24 PC teams in Catalonia (Spain), randomly assigned to the intervention group (1:1), and community pharmacies in the catchment areas of the intervention PC teams. Healthcare professionals in the intervention group will apply the intervention to all patients who receive a new prescription for cardiovascular disease or diabetes treatment (no other prescription from the same pharmacological group in the previous 6 months). All the study variables will be collected from real-world databases for the 12 months before and after receiving a new prescription. Effectiveness analyses will assess impact on initiation, secondary adherence, cardiovascular risk, clinical parameters and cardiovascular events. Cost-effectiveness analyses will be conducted as part of the cRCT from a healthcare and societal perspective in terms of extra cost per cardiovascular risk reduction and improved adherence; all analyses will be clustered. Economic models will be built to assess the long-term cost-effectiveness of the IMA intervention, in terms of extra cost for gains in QALY and life expectancy, using clinical trial data and data from previous studies.

Discussion

The IMA-cRCT represents an innovative approach to the design and evaluation of behavioural interventions that use the principles of complex interventions, pragmatic trials and implementation research. This study will provide evidence on the IMA intervention and on a new methodology for developing and evaluating complex interventions. The results of the study will be disseminated among stakeholders to facilitate its transferability to clinical practice.

Trial registration

ClinicalTrials.gov, NCT05026775. Registered 30th August 2021.
Characterisation of Staphylococci species from neonatal blood cultures in low- and middle-income countries
Authors: Sands Kirsty , Carvalho Maria J. , Spiller Owen B. , Portal Edward A. R. , Thomson Kathryn , Watkins William John , Mathias Jordan , Dyer Calie , Akpulu Chinenye , Andrews Robert , Ferreira Ana , Hender Thomas , Milton Rebecca , Nieto Maria , Zahra Rabaab , Shirazi Haider , Muhammad Adil , Akif Shermeen , Jan Muhammad Hilal , Iregbu Kenneth , Modibbo Fatima , Uwaezuoke Stella , Chan Grace J. , Bekele Delayehu , Solomon Semaria , Basu Sulagna , Nandy Ranjan Kumar , Naha Sharmi , Mazarati Jean-Baptiste , Rucogoza Aniceth , Gaju Lucie , Mehtar Shaheen , Bulabula Andre N. H. , Whitelaw Andrew ,   BARNARDS Group, Walsh Timothy R.
Published: July 2022

Background

In low- and middle-income countries (LMIC)Staphylococcus aureusis regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB).

Methods

We characterised GPB isolates from neonatal blood cultures from LMICs in Africa (Ethiopia, Nigeria, Rwanda, and South Africa) and South-Asia (Bangladesh and Pakistan) between 2015–2017. We determined minimum inhibitory concentrations and performed whole genome sequencing (WGS) on Staphylococci isolates recovered and clinical data collected related to the onset of sepsis and the outcome of the neonate up to 60 days of age.

Results

From the isolates recovered from blood cultures, Staphylococci species were most frequently identified. Out of 100S. aureusisolates sequenced, 18 different sequence types (ST) were found which unveiled two small epidemiological clusters caused by methicillin resistantS. aureus(MRSA) in Pakistan (ST8) and South Africa (ST5),both with high mortality (n = 6/17). One-third ofS. aureuswas MRSA, with methicillin resistance also detected inStaphylococcus epidermidis, Staphylococcus haemolyticusandMammaliicoccus sciuri.Through additional WGS analysis we report a cluster ofM. sciuriin Pakistan identified between July-November 2017.

Conclusions

In total we identified 14 different GPB bacterial species, however Staphylococci was dominant. These findings highlight the need of a prospective genomic epidemiology study to comprehensively assess the true burden of GPB neonatal sepsis focusing specifically on mechanisms of resistance and virulence across species and in relation to neonatal outcome.
Iatrogenic genito-urinary fistula following cesarean birth in nine sub-Saharan African countries: a retrospective review
Authors: Ngongo Carrie J. , Raassen Thomas J. I. P. , Mahendeka Marietta , Lombard Ladeisha , van Roosmalen Jos
Published: July 2022

Background

Genito-urinary fistulas may occur as complications of obstetric surgery. Location and circumstances can indicate iatrogenic origin as opposed to pressure necrosis following prolonged, obstructed labor.

Methods

This retrospective review focuses on 787 women with iatrogenic genito-urinary fistulas among 2942 women who developed fistulas after cesarean birth between 1994 and 2017. They are a subset of 5469 women who sought obstetric fistula repair between 1994 and 2017 in Tanzania, Uganda, Kenya, Malawi, Rwanda, Somalia, South Sudan, Zambia, and Ethiopia. We compared genito-urinary fistula classifications following vaginal birth to classifications following cesarean birth. We assessed whether and how the proportion of iatrogenic genito-urinary fistula was changing over time among women with fistula, comparing women with iatrogenic fistulas to women with fistulas attributable to pressure necrosis. We used mixed effects logistic regression to model the rise in iatrogenic fistula among births resulting in fistula and specifically among cesarean births resulting in fistula.

Results

Over one-quarter of women with fistula following cesarean birth (26.8%, 787/2942) had an injury caused by surgery rather than pressure necrosis due to prolonged, obstructed labor. Controlling for age, parity, and previous abdominal surgery, the odds of iatrogenic origin nearly doubled over time among all births resulting in fistula (aOR 1.94; 95% CI 1.48–2.54) and rose by 37% among cesarean births resulting in fistula (aOR 1.37; 95% CI 1.02–1.83). In Kenya and Rwanda the rise of iatrogenic injury outpaced the increasing frequency of cesarean birth.

Conclusions

Despite the strong association between obstetric fistula and prolonged, obstructed labor, more than a quarter of women with fistula after cesarean birth had injuries due to surgical complications rather than pressure necrosis. Risks of iatrogenic fistula during cesarean birth reinforce the importance of appropriate labor management and cesarean decision-making. Rising numbers of iatrogenic fistulas signal a quality crisis in emergency obstetric care. Unaddressed, the impact of this problem will grow as cesarean births become more common.
One-stage tubularized urethroplasty using the free inner plate of the foreskin in the treatment of proximal hypospadias
Authors: Shi Tong , Lin Yan-Kun , Bao Qiao , Lao Wei-Hua , Ouyang Ke-Yu
Published: July 2022

Objective

This study summarizes the short-term efficacy of the one-stage tubularized urethroplasty using the free inner in proximal hypospadias.

Methods

A retrospective analysis was conducted on 42 patients with proximal hypospadias. All cases were treated with one-stage tubularized urethroplasty from January 2020 to June 2021. The postoperative complications like urethral fistula, urethral stricture, diverticulum, and split penis head were recorded.

Results

Patients were followed up for 3 to 15 months (an average of 8.5 months). A total of 26 cases (62%) were repaired without any complication. Five patients (11.9%) developed urinary fistulas and underwent secondary repair: three cases with anastomotic fistulas and two cases of coronal fistulas. Nine patients (21.4%) had stenosis of the head segment of the penis, six (14.3%) had stenosis that was relieved by urethral dilatation combined with topical mometasone furoate 1 month after urethral catheter removal. Two patients (4.8%) had severe stenosis with secondary surgical stenosis incision, and one (2.4%) had combined urethral diverticulum in which urethral stenosis incision and diverticulectomy were performed.

Conclusions

Tubularized urethroplasty using the free inner bears the advantages of easy access, reduced short-term complications, low incidence of diverticula.
COVID-19 vaccine hesitancy and patient self-advocacy: a statistical analysis of those who can and can’t get vaccinated
Authors: Ashwell Douglas , Cullinane Joanna , Croucher Stephen M.
Published: July 2022

Background

This study applies the Patient Self-Advocacy scale to investigate vaccine hesitancy in New Zealand. Due to New Zealand’s very limited tertiary hospital system and vulnerable populations, the Government’s strategy to address COVID-19 has been to prevent the virus from entering the nation and to eliminate it when it does cross the border. Therefore, there is no opportunity for the nation to generate any acquired immunity through exposure. To transition from closed borders, New Zealand will need to run a highly successful national vaccination programme and this needs to have the ability to drive influential public health messaging to the targeted places within the communities where vaccine hesitancy most exists.

Methods

This study employed statistical methods. A nationally representative survey of adults in New Zealand (n = 1852) was collected via Qualtrics. Independent samples t-tests, and multiple regression were used to explore the research questions.

Results

Those who identify as medically able to be vaccinated expressed significantly higher confidence in the COVID-19 vaccine than those who identified as unable to be vaccinated. Patient-self advocacy had a positive effect on vaccine confidence. Individuals who identify as able to be vaccinated have less hesitancy. Demographics had various effects on vaccine hesitancy.

Conclusion

The research highlights particularly important insights into vaccine hesitancy related to patient self-advocacy behaviours, and various demographic variables such as political affiliation. In addition, the research adds further clarity on how and why New Zealanders have responded to the COVID-vaccine. Finally, the importance of vaccine literacy is discussed.