bluuebunny/crossref_metadata_2025 huggingface dataset:
Video-assisted anal fistula treatment versus fistulectomy and sphincter repair in the treatment of high cryptoglandular anal fistula: a randomized clinical study
Authors: Sørensen Karam M , Möller Sören , Qvist Niels
Published: September 2021

Background

Video-assisted anal fistula treatment (VAAFT) may have a recurrence rate comparable to that of fistulectomy and sphincter repair (FSR) in the treatment of high anal fistula and with potential advantages in wound healing, functional outcome and quality of life. The aim and objectives of the study are to compare the outcome of VAAFT with that of FSR for high cryptoglandular anal fistula.

Methods

This was a single-centre randomized controlled trial of adults with high anal fistula comparing FSR with VAAFT. Primary outcome was fistula recurrence. Secondary outcomes were results of anal manometry, quality of life and faecal continence. A power calculation of 33 patients in each arm (1 : 1) was based on recurrence in the FSR and VAAFT groups of 5 per cent and 30 per cent respectively. Follow-up at 6 months after surgery included physical examination, MRI, anal manometry, quality-of-life assessment (RAND SF 36 questionnaire) and faecal-continence assessment (Wexner score).

Results

The study was terminated early due to high recurrence rates in both groups. A total of 45 patients were included. Recurrence rates were 65 per cent for VAAFT and 27 per cent for FSR, with hazard ratio 4.18 (P = 0.016). Length of the fistula was a risk factor with an association with recurrence (hazard ratio 1.8, P = 0.020). There were significant differences in quality of life in favour of FSR and in anal manometry in favour of VAAFT with a significant improvement in Wexner score in both groups.

Conclusion

FSR was associated with a lower recurrence rate than VAAFT in the management of complex anal fistulae in this single-centre study but the study was terminated early due to higher than predicted recurrence rate in both groups.

Registration number

NCT02585167 (http://www.clinicaltrials.org).
Social Work as a Transformative Science: The Importance of Relevance Structures in Knowledge Production
Authors: Drilling Matthias
Published: September 2021

This article focuses on the question of how cooperative knowledge production takes place and, in particular, how novel knowledge is formed and implemented in organisational action. According to the current state of knowledge, this process, which results in a change in the way an organisation acts, is called social innovation. The framework for argumentation and reflection is provided by studies from the social work sciences on cooperative knowledge production and social innovation, as well as studies on the hybridity of knowledge and its interaction with the knowledge resources of scientific and non-scientific actors. Relevance structures are recognised in this article as a fundamental structure in the field of cooperative knowledge production; they significantly influence the question of how and when new knowledge leads to social innovation. A research project on homelessness serves as an example. Homelessness has been a research topic in Europe for many years. In Switzerland, however, there are hardly any scientifically sound studies and there are also few documented methods of action in practice. From this point of view, homelessness in Switzerland is therefore in need of innovation.
A Systematic Review of Empirical Research on Transracial Adoption in South Africa
Authors: Luyt Jean , Swartz Leslie , Vogel Lodewyk
Published: September 2021

Transracial adoption is a relatively new and controversial practice in South Africa. We undertook a systematic review of empirical research by adhering to the preferred reporting items for systematic reviews and meta-analyses guideline. A comprehensive literature search was conducted on research, both peer-reviewed and unpublished academic work, between January 1991 and April 2021. We report on the scientific nature, rigour, quality and scope of studies of the items found and outline the themes which emerge from the empirical research. These include attitudes towards transracial adoption, the experiences of adoptive parents and transracial adoptees as well as recommendations for practice. Different theoretical paradigms, variable methodology, small sample sizes of poorly defined target groups impact negatively on comparability and generalisability of results. This research fails to engage with the specificities that might impact on successful outcomes for transracially adopted families and guide professional practice including post-adoption support. Developing this research field will require large-scale studies on the outcomes for transracial adoptees and adoptive families, and research using the comparable methodology and theoretical frameworks. Such research can guide local policies and practices in South Africa and will enhance the international research into transracial adoption.
Bacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma
Authors: Ntranos Achilles , Park Hye-Jin , Wentling Maureen , Tolstikov Vladimir , Amatruda Mario , Inbar Benjamin , Kim-Schulze Seunghee , Frazier Carol , Button Judy , Kiebish Michael A , Lublin Fred , Edwards Keith , Casaccia Patrizia
Published: September 2021

The identification of intestinal dysbiosis in patients with neurological and psychiatric disorders has highlighted the importance of gut–brain communication, and yet the question regarding the identity of the components responsible for this cross-talk remains open. We previously reported that relapsing remitting multiple sclerosis patients treated with dimethyl fumarate have a prominent depletion of the gut microbiota, thereby suggesting that studying the composition of plasma and CSF samples from these patients may help to identify microbially derived metabolites.

We used a functional xenogeneic assay consisting of cultured rat neurons exposed to CSF samples collected from multiple sclerosis patients before and after dimethyl fumarate treatment to assess neurotoxicity and then conducted a metabolomic analysis of plasma and CSF samples to identify metabolites with differential abundance. A weighted correlation network analysis allowed us to identify groups of metabolites, present in plasma and CSF samples, whose abundance correlated with the neurotoxic potential of the CSF. This analysis identified the presence of phenol and indole group metabolites of bacterial origin (e.g. p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) as potentially neurotoxic and decreased by treatment. Chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity. Clinical, radiological and cognitive test metrics were also collected in treated patients at follow-up visits. Improved MRI metrics, disability and cognition were only detected in dimethyl fumarate-treated relapsing remitting multiple sclerosis patients. The levels of the identified metabolites of bacterial origin (p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) were inversely correlated to MRI measurements of cortical volume and directly correlated to the levels of neurofilament light chain, an established biomarker of neurodegeneration.

Our data suggest that phenol and indole derivatives from the catabolism of tryptophan and phenylalanine are microbially derived metabolites, which may mediate gut–brain communication and induce neurotoxicity in multiple sclerosis.
Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years
Authors: Ziegler Dan , Bönhof Gidon J , Strom Alexander , Straßburger Klaus , Karusheva Yanislava , Szendroedi Julia , Roden Michael
Published: September 2021

It has traditionally been suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible.

Participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 350/570) and age-matched glucose-tolerant control individuals (Control 1/Control 2: n = 114/190) were assessed using nerve conduction studies, thermal detection thresholds, vibration perception thresholds, neuropathy symptom scores, neuropathy disability scores and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1/type 2 diabetes: n = 102/226; Control 1/Control 2: n = 109/208). Subsets of participants with type 1/type 2 diabetes were followed for 5 years (n = 184/307; IENFD subset: n = 18/69). DSPN was defined by the Toronto Consensus criteria.

At baseline, DSPN was present in 8.1% and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centiles of the controls were the IENFD (13.7%) and individual nerve conduction studies (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar vibration perception thresholds (17.5%), and individual nerve conduction studies (up to 11.8%) in those with type 2 diabetes, whereas thermal detection threshold abnormalities did not differ between the control and diabetes groups. After 5 years, the highest progression rates from the normal to the abnormal range in type 2 diabetes participants were found for IENFD (18.8%) by −4.1 ± 2.8 fibres/mm, malleolar vibration perception threshold (18.6%) by 9.1 ± 20.2 µm and nerve conduction studies (15.0%) by 3.7 ± 1.5 points, while vice versa the highest regression rates were observed for neuropathy disability scores (11.2%) by −3.1 ± 1.3 points, sural nerve amplitudes (9.1%) by 4.7 ± 3.0 µV, IENFD (8.7%) by 1.4 ± 1.3 fibres/mm, and neuropathy symptom scores (8.2%) by −5.8 ± 1.6 points. In type 1 diabetes participants, no major progression was seen after 5 years, but subclinical DSPN regressed in 10.3%.

These findings point to early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5 years, peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.
Ventilation practices in burn patients—an international prospective observational cohort study
Authors: Glas Gerie J , Horn Janneke , Hollmann Markus W , Preckel Benedikt , Colpaert Kirsten , Malbrain Manu , Neto Ary Serpa , Asehnoune Karim , de Abreu Marcello Gamma , Martin-Loeches Ignacio , Pelosi Paolo , Sjöberg Folke , Binnekade Jan M , Cleffken Berry , Juffermans Nicole P , Knape Paul , Loef Bert G , Mackie David P , Enkhbaatar Perenlei , Depetris Nadia , Perner Anders , Herrero Eva , Cachafeiro Lucia , Jeschke Marc , Lipman Jeffrey , Legrand Matthieu , Horter Johannes , Lavrentieva Athina , Kazemi Alex , Guttormsen Anne Berit , Huss Frederik , Kol Mark , Wong Helen , Starr Therese , De Crop Luc , de Oliveira Filho Wilson , Manoel Silva Junior João , Grion Cintia M C , Burnett Marjorie , Mondrup Frederik , Ravat Francois , Fontaine Mathieu , Floch Renan Le , Jeanne Mathieu , Bacus Morgane , Chaussard Maïté , Lehnhardt Marcus , Mikhail Bassem Daniel , Gille Jochen , Sharkey Aidan , Trommel Nicole , Reidinga Auke C , Vieleers Nadine , Tilsley Anna , Onarheim Henning , Bouza Maria Teresa , Agrifoglio Alexander , Fredén Filip , Palmieri Tina , Painting Lynda E , Schultz Marcus J ,   LAMiNAR investigators
Published: September 2021

Background

It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28).

Methods

This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (VT) was defined as VT ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between VT and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma.

Results

A total of 160 patients from 28 ICUs in 16 countries were included. Low VT was used in 74% of patients, median VT size was 7.3 [interquartile range (IQR) 6.2–8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0–26), without a difference between ventilation with low or high VT (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O.

Conclusion

In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low VT was not associated with a reduction in VFD-28.

Trial registration

Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.
Assessing Programmatic Mentoring: Requiem for Carmen
Authors: Means Coleman Robin R , Reyes Jennifer McGee
Published: September 2021

This essay is not about getting good mentoring. Rather, it is about the ways in which institutions must invest in providing resources for professional success and wellness, with a particular understanding of the needs of women of color. To ensure faculty retention and success, institutions must not only provide resources but also engage in exacting assessment practices to ensure programmatic efficacy.
Enshrining Terror for the Nation: Affect and Nationalism at the National September 11 Memorial and Museum
Authors: Gruenewald Tim
Published: September 2021

The National September 11 Memorial and Museum (9/11 MM) employs affective rhetoric to enshrine the trauma of September 11 in support of U.S. nationalism. Applying Brian Massumi's understanding of affect as intensity, I examine how the site's rhetoric amplifies affect. The memorial pools and many signifiers of destruction magnify affective intensity through scale and repetition. The 9/11 MM continues its affective onslaught through an excessive number of shocking visuals and narrative details in its historical exhibition. The site’s affective intensity culminates in a non-linear and non-narrative memorial space of seemingly infinite individualized mourning. The article discusses the site's political and social impact by considering Nigel Thrift's idea of affect in the built environment as imbedded thought and Georg Böhme's theory of atmosphere, understood as the reciprocal relationship between affective urban space and its impact on people.
Searching for sustainable cities: residents’ perceptions on the implementation of sustainable cities in Malaysia
Authors: Tedong Peter Aning , Zyed Zafirah Al-Sadat
Published: September 2021

There has been considerable interest in the research of sustainable cities in developing countries such as Malaysia. This paper will review urban residents’ perceptions of the ways that sustainable cities are being planned and produced in Malaysia. In particular, this article analyses urban residents’ perceptions of planners’ roles in the context of diverse aspirations for sustainable cities. Data collected from in-depth interviews and survey revealed that the communication between urban residents and planners tends to be ‘one way’ and there are ‘too many’ unnecessary political intervention in planning for sustainable cities. Although public participation allows urban residents to participate in the planning process, the residents’ opinions tend to be ignored as there is a minority but a powerful and affluent group that dominated the process. Our data also revealed that neighbourhood planning tends to include ‘everything’ under the umbrella of sustainability, but with little practical execution on the ground. Thus, we can conclude that the implementation of sustainable development is still a challenge in Malaysian cities.
Coarse-to-Fine(r) Automatic Familiar Face Recognition in the Human Brain
Authors: Yan Xiaoqian , Goffaux Valérie , Rossion Bruno
Published: September 2021

At what level of spatial resolution can the human brain recognize a familiar face in a crowd of strangers? Does it depend on whether one approaches or rather moves back from the crowd? To answer these questions, 16 observers viewed different unsegmented images of unfamiliar faces alternating at 6 Hz, with spatial frequency (SF) content progressively increasing (i.e., coarse-to-fine) or decreasing (fine-to-coarse) in different sequences. Variable natural images of celebrity faces every sixth stimulus generated an objective neural index of single-glanced automatic familiar face recognition (FFR) at 1 Hz in participants’ electroencephalogram (EEG). For blurry images increasing in spatial resolution, the neural FFR response over occipitotemporal regions emerged abruptly with additional cues at about 6.3–8.7 cycles/head width, immediately reaching amplitude saturation. When the same images progressively decreased in resolution, the FFR response disappeared already below 12 cycles/head width, thus providing no support for a predictive coding hypothesis. Overall, these observations indicate that rapid automatic recognition of heterogenous natural views of familiar faces is achieved from coarser visual inputs than generally thought, and support a coarse-to-fine FFR dynamics in the human brain.
Functional Neural Correlates of a Useful Field of View (UFOV)-Based fMRI Task in Older Adults
Authors: Kraft Jessica N , Albizu Alejandro , O’Shea Andrew , Hausman Hanna K , Evangelista Nicole D , Boutzoukas Emanuel , Hardcastle Cheshire , Van Etten Emily J , Bharadwaj Pradyumna K , Song Hyun , Smith Samantha G , DeKosky Steven , Hishaw Georg A , Wu Samuel , Marsiske Michael , Cohen Ronald , Alexander Gene E , Porges Eric , Woods Adam J
Published: September 2021

Declines in processing speed performance occur in aging and are a critical marker of functional independence in older adults. Studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline. Despite its efficacy, little is known about the neural correlates of this task. Within the current study, 233 healthy older adults completed a UFOV-based task while undergoing functional magnetic resonance imaging (fMRI). During the “stimulus” portion of this task, participants must identify a target in the center of the screen and the location of a target in the periphery, among distractors. During the “probe” portion, participants must decide if the object in the center and the location of the target in the periphery were identical to the “stimulus” screen. Widespread bilateral whole-brain activation was observed when activation patterns of the “probe” contrast were subtracted from the “stimulus” contrast. Conversely, the subtraction of “stimulus” from “probe” was associated with discrete activation patterns consisting of 13 clusters. Additionally, when evaluating the variance associated with task accuracy, specific subregions were identified that may be critical for task performance. Our data elucidate the functional neural correlates of a UFOV-based task, a task used in both cognitive training paradigms and assessment of function.
Functional Abnormality of the Executive Control Network in Individuals With Obesity During Delay Discounting
Authors: Zhang Wenchao , Li Guanya , Manza Peter , Hu Yang , Wang Jia , Lv Ganggang , He Yang , von Deneen Karen M , Yu Juan , Han Yu , Cui Guangbin , Volkow Nora D , Nie Yongzhan , Ji Gang , Wang Gene-Jack , Zhang Yi
Published: September 2021

Individuals with obesity (OB) prefer immediate rewards of food intake over the delayed reward of healthy well-being achieved through diet management and physical activity, compared with normal-weight controls (NW). This may reflect heightened impulsivity, an important factor contributing to the development and maintenance of obesity. However, the neural mechanisms underlying the greater impulsivity in OB remain unclear. Therefore, the current study employed functional magnetic resonance imaging with a delay discounting (DD) task to examine the association between impulsive choice and altered neural mechanisms in OB. During decision-making in the DD task, OB compared with NW had greater activation in the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex, which was associated with greater discounting rate and weaker cognitive control as measured with the Three-Factor Eating Questionnaire (TFEQ). In addition, the association between DLPFC activation and cognitive control (TFEQ) was mediated by discounting rate. Psychophysiological interaction analysis showed decreased connectivity of DLPFC–inferior parietal cortex (within executive control network [ECN]) and angular gyrus–caudate (ECN–reward) in OB relative to NW. These findings reveal that the aberrant function and connectivity in core regions of ECN and striatal brain reward regions underpin the greater impulsivity in OB and contribute to abnormal eating behaviors.
Impact of In Utero Exposure to Antiepileptic Drugs on Neonatal Brain Function
Authors: Tokariev Anton , Breakspear Michael , Videman Mari , Stjerna Susanna , Scholtens Lianne H , van den Heuvel Martijn P , Cocchi Luca , Vanhatalo Sampsa
Published: September 2021

In utero brain development underpins brain health across the lifespan but is vulnerable to physiological and pharmacological perturbation. Here, we show that antiepileptic medication during pregnancy impacts on cortical activity during neonatal sleep, a potent indicator of newborn brain health. These effects are evident in frequency-specific functional brain networks and carry prognostic information for later neurodevelopment. Notably, such effects differ between different antiepileptic drugs that suggest neurodevelopmental adversity from exposure to antiepileptic drugs and not maternal epilepsy per se. This work provides translatable bedside metrics of brain health that are sensitive to the effects of antiepileptic drugs on postnatal neurodevelopment and carry direct prognostic value.
Symmetry Processing in the Macaque Visual Cortex
Authors: Audurier Pauline , Héjja-Brichard Yseult , De Castro Vanessa , Kohler Peter J , Norcia Anthony M , Durand Jean-Baptiste , Cottereau Benoit R
Published: September 2021

Symmetry is a highly salient feature of the natural world that is perceived by many species. In humans, the cerebral areas processing symmetry are now well identified from neuroimaging measurements. Macaque could constitute a good animal model to explore the underlying neural mechanisms, but a previous comparative study concluded that functional magnetic resonance imaging responses to mirror symmetry in this species were weaker than those observed in humans. Here, we re-examined symmetry processing in macaques from a broader perspective, using both rotation and reflection symmetry embedded in regular textures. Highly consistent responses to symmetry were found in a large network of areas (notably in areas V3 and V4), in line with what was reported in humans under identical experimental conditions. Our results suggest that the cortical networks that process symmetry in humans and macaques are potentially more similar than previously reported and point toward macaque as a relevant model for understanding symmetry processing.
False Coronavirus Disease 2019 Cases due to Contamination by Inactivated Virus Vaccine
Authors: To Kelvin Kai-Wang , Li Xin , Lung David Christopher , Ip Jonathan Daniel , Chan Wan-Mui , Chu Allen Wing-Ho , Yip Cyril Chik-Yan , Chen Jonathan H K , Poon Rosana Wing-Shan , Tsoi Hoi-Wah , Lai Raymond Wai-Man , To Wing-Kin , Ren Lili , Li Mingkun , Cao Yunlong , Xie Xiaoliang Sunney , Jin Dong-Yan , Yuen Kwok-Yung
Published: September 2021

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.
Clinical and Infection Prevention Applications of Severe Acute Respiratory Syndrome Coronavirus 2 Genotyping: An Infectious Diseases Society of America/American Society for Microbiology Consensus Review Document
Authors: Greninger Alexander L , Dien Bard Jennifer , Colgrove Robert C , Graf Erin H , Hanson Kimberly E , Hayden Mary K , Humphries Romney M , Lowe Christopher F , Miller Melissa B , Pillai Dylan R , Rhoads Daniel D , Yao Joseph D , Lee Francesca M
Published: September 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged into a world of maturing pathogen genomics, with >2 million genomes sequenced at this writing. The rise of more transmissible variants of concern that affect vaccine and therapeutic effectiveness has led to widespread interest in SARS-CoV-2 evolution. Clinicians are also eager to take advantage of the information provided by SARS-CoV-2 genotyping beyond surveillance purposes. Here, we review the potential role of SARS-CoV-2 genotyping in clinical care. The review covers clinical use cases for SARS-CoV-2 genotyping, methods of SARS-CoV-2 genotyping, assay validation and regulatory requirements, clinical reporting for laboratories, and emerging issues in clinical SARS-CoV-2 sequencing. While clinical uses of SARS-CoV-2 genotyping are currently limited, rapid technological change along with a growing ability to interpret variants in real time foretell a growing role for SARS-CoV-2 genotyping in clinical care as continuing data emerge on vaccine and therapeutic efficacy.
Building Global Capacity to Conduct Pathology-Based Postmortem Examination: Establishing a New Training Hub for Minimally Invasive Tissue Sampling
Authors: Paganelli Christina R , Parlberg Lindsay , Goco Norman J , Ritter Jana M , Martines Roosecelis B , Zaki Sherif R , Walong Edwin , Ochieng Washington , Inyangala Dennis , Barake Walter , Wachiury Cyrus , Rakislova Natalia , Marimon Lorena , Ferrando Melania , Ordi Jaume , McClure Elizabeth
Published: September 2021

Background

Minimally invasive tissue sampling (MITS), an alternative to complete diagnostic autopsy, is a pathology-based postmortem examination that has been validated in low- and middle-income countries (LMICs) and can provide accurate cause of death information when used with other data. The MITS Surveillance Alliance was established in 2017 with the goal to expand MITS globally by increasing training capacity, accessibility, and availability in LMICs. Between January 2019 and May 2020, the MITS Surveillance Alliance convened a multidisciplinary team of technical advisors to attain this goal.

Methods

This article describes the process used to develop criteria and identify an optimal location for a MITS training hub, establish a cadre of LMIC-based trainers, refine standardized MITS sample collection protocols, develop a training program, and release a telepathology platform for quality assessment of MITS histological samples.

Results

Results include the creation of a training hub and curriculum, with a total of 9 pathologists and technicians trained as part of the training of the trainers. Those trainers trained 15 participants from seven MITS projects representing 6 LMICs trained in MITS sample collection. The 15 participants have gone on to train more than 50 project-level staff in MITS sample collection.

Conclusions

Lessons learned include an appreciation for using an iterative process for establishing standardized procedures, creating opportunities for all stakeholders to deliver critical feedback, and highlighting the importance of complementing in-person trainings with ongoing technical assistance.
High-Resolution Genomic Profiling of Carbapenem-Resistant Klebsiella pneumoniae Isolates: A Multicentric Retrospective Indian Study
Authors: Nagaraj Geetha , Shamanna Varun , Govindan Vandana , Rose Steffimole , Sravani D , Akshata K P , Shincy M R , Venkatesha V T , Abrudan Monica , Argimón Silvia , Kekre Mihir , Underwood Anthony , Aanensen David M , Ravikumar K L ,   NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, Abudahab Khalil , Harste Harry , Muddyman Dawn , Taylor Ben , Wheeler Nicole , David Sophia , Donado-Godoy Pilar , Bernal Johan Fabian , Arevalo Alejandra , Valencia Maria Fernanda , Osma Castro Erik C D , Ravishankar K N , Okeke Iruka N , Oaikhena Anderson O , Afolayan Ayorinde O , Ajiboye Jolaade J , Odih Erkison Ewomazino , Carlos Celia , Lagrada Marietta L , Macaranas Polle Krystle V , Olorosa Agnettah M , Gayeta June M , Herrera Elmer M
Published: September 2021

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a threat to public health in India because of its high dissemination, mortality, and limited treatment options. Its genomic variability is reflected in the diversity of sequence types, virulence factors, and antimicrobial resistance (AMR) mechanisms. This study aims to characterize the clonal relationships and genetic mechanisms of resistance and virulence in CRKP isolates in India.

Materials and Methods

We characterized 344 retrospective K. pneumoniae clinical isolates collected from 8 centers across India collected in 2013–2019. Susceptibility to antibiotics was tested with VITEK 2. Capsular types, multilocus sequence type, virulence genes, AMR determinants, plasmid replicon types, and a single-nucleotide polymorphism phylogeny were inferred from their whole genome sequences.

Results

Phylogenetic analysis of the 325 Klebsiella isolates that passed quality control revealed 3 groups: K. pneumoniae sensu stricto (n = 307), K. quasipneumoniae (n = 17), and K. variicola (n = 1). Sequencing and capsular diversity analysis of the 307 K. pneumoniae sensu stricto isolates revealed 28 sequence types, 26 K-locus types, and 11 O-locus types, with ST231, KL51, and O1V2 being predominant. blaOXA-48-like and blaNDM-1/5 were present in 73.2% and 24.4% of isolates, respectively. The major plasmid replicon types associated with carbapenase genes were IncF (51.0%) and Col group (35.0%).

Conclusion

Our study documents for the first time the genetic diversity of K and O antigens circulating in India. The results demonstrate the practical applicability of genomic surveillance and its utility in tracking the population dynamics of CRKP. It alerts us to the urgency for longitudinal surveillance of these transmissible lineages.
Good Financial Grant Practice: A Tool for Developing and Demonstrating Institutional Financial and Grant Management Capacity in Global Health
Authors: Harste Harry J , Kiff Genevieve , Okeke Iruka N , Adebiyi Akindele O , Ravikumar K L , Nagaraj Geetha , Ajiboye Jolaade J , Osma Castro Erik C D , Herrera Elmer , Aanensen David M ,   NIHR Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance, Abudahab Khalil , Abrudan Monica , Argimón Silvia , Kekre Mihir , Muddyman Dawn , Taylor Ben , Underwood Anthony , Wheeler Nicole , Sophia David , Donado-Godoy Pilar , Fabian Bernal Johan , Arevalo Alejandra , Fernanda Valencia Maria , Shamanna Varun , Govindan Vandana , Prabhu Akshata , Sravani D , Shincy M R , Rose Steffimole , Ravishankar K N , Oaikhena Anderson O , Afolayan Ayorinde O , Ewomazino Odih Erkison , Carlos Celia , Lagrada Marietta L , Macaranas Polle Krystle V , Olorosa Agnettah M , Gayeta June M
Published: September 2021

The administration and governance of grant funding across global health organizations presents enormous challenges. Meeting these challenges is crucial to ensuring that funds are used in the most effective way to improve health outcomes, in line with the United Nations’ Sustainable Development Goal 3, “Ensure healthy lives and promote well-being for all at all ages.” The Good Financial Grant Practice (GFGP) Standard (ARS 1651) is the world’s first and, currently, only international standard for the financial governance and management of grant funding. Through consensus building and global harmonization between both low- and middle-income and high-income country players, the GFGP Standard has achieved a leveling impact: GFGP applies equally to, and can be implemented by, all types of organization, regardless of location, size, or whether they predominantly give or receive funding.

GFGP can be used as a tool for addressing some of the challenges of the current funding model. Here, we describe our experiences and lessons learned from implementing GFGP across 4 diverse research institutions in India, Nigeria, Colombia, and the Philippines as part of our National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance.
Enteric Illness Outbreaks Reported Through the National Outbreak Reporting System—United States, 2009–2019
Authors: Wikswo Mary E , Roberts Virginia , Marsh Zachary , Manikonda Karunya , Gleason Brigette , Kambhampati Anita , Mattison Claire , Calderwood Laura , Balachandran Neha , Cardemil Cristina , Hall Aron J
Published: September 2021

Background

The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. This study describes enteric illness outbreaks reported during 11 years of surveillance.

Methods

We extracted finalized reports from NORS for outbreaks occurring during 2009–2019. Outbreaks were included if caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis.

Results

A total of 38 395 outbreaks met inclusion criteria, increasing from 1932 in 2009 to 3889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n = 23 812; 62%) and contaminated food (n = 9234; 24%). Norovirus was the most commonly reported etiology, reported in 22 820 (59%) outbreaks, followed by Salmonella (n = 2449; 6%) and Shigella (n = 1171; 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (P < .0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and Escherichia coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). Case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%).

Conclusions

Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.
A Quest for Due Process Doctrine in Vietnamese Law: From Soviet Legacy to Global Constitutionalism
Authors: Bui Dat T
Published: September 2021

Due process—the ‘soul’ of a modern constitution—was not seriously taken into account under purely socialist legal systems in general as well as in pre-2013 Vietnamese constitutions in particular. Since the 2013 Constitution, Vietnamese jurisprudence has incorporated the human rights-limitation principle (substantive due process) for the first time and strengthened the application of universal fair trial rights (procedural due process). This constitutional development is the result of the fact that, over the past two decades, the class-based perception of human rights has been increasingly less important and has been almost replaced by universalism. This article claims that, because of the influence of Soviet jurisprudence, the Vietnamese version of due process has been characterized by the fact that human rights could be arbitrarily trumped by public interests and that fair trial rights have been problematically limited to criminal proceedings and almost ignored in non-criminal procedures. This article analyses the importance of, and the challenges involved in, incorporating the human rights-limitation principle into the 2013 Constitution and argues for an extension of fair trial rights to all kinds of criminal, civil, administrative, and mixed procedures in keeping with global constitutionalism.
The effect of health shocks on labour market outcomes in Russia
Authors: Aleksandrova Ekaterina , Bagranova Venera , Gerry Christopher J
Published: September 2021

This study examines the effects of individual health shocks on labour market outcomes in the Russian Federation during the period 2000–2018. Employing data from the Russia Longitudinal Monitoring Survey—Higher School of Economics, we demonstrate that adverse health shocks have negative consequences for employment, wages, and income. We find that the effects are strongest for males, the less educated, those on lower incomes, those in middle-ranking and professional occupations, and for those experiencing the most severe health shocks. However, consistent with our knowledge of the Russian labour market, we also observe that the wage and income elasticities are considerably higher than the employment elasticities and above those reported for other countries. Understanding how to attenuate the negative labour market consequences associated with health shocks is paramount and we, therefore, consider the potential role that labour, health and social policies can play in mitigating risk.
Artificial Intelligence and Mapping a New Direction in Laboratory Medicine: A Review
Authors: Herman Daniel S , Rhoads Daniel D , Schulz Wade L , Durant Thomas J S
Published: September 2021

Background

Modern artificial intelligence (AI) and machine learning (ML) methods are now capable of completing tasks with performance characteristics that are comparable to those of expert human operators. As a result, many areas throughout healthcare are incorporating these technologies, including in vitro diagnostics and, more broadly, laboratory medicine. However, there are limited literature reviews of the landscape, likely future, and challenges of the application of AI/ML in laboratory medicine.

Content

In this review, we begin with a brief introduction to AI and its subfield of ML. The ensuing sections describe ML systems that are currently in clinical laboratory practice or are being proposed for such use in recent literature, ML systems that use laboratory data outside the clinical laboratory, challenges to the adoption of ML, and future opportunities for ML in laboratory medicine.

AI and ML have and will continue to influence the practice and scope of laboratory medicine dramatically. This has been made possible by advancements in modern computing and the widespread digitization of health information. These technologies are being rapidly developed and described, but in comparison, their implementation thus far has been modest. To spur the implementation of reliable and sophisticated ML-based technologies, we need to establish best practices further and improve our information system and communication infrastructure. The participation of the clinical laboratory community is essential to ensure that laboratory data are sufficiently available and incorporated conscientiously into robust, safe, and clinically effective ML-supported clinical diagnostics.
Optimizing Available Tools for Achieving Result Standardization: Value Added by Joint Committee on Traceability in Laboratory Medicine (JCTLM)
Authors: Panteghini Mauro , Braga Federica , Camara Johanna E , Delatour Vincent , Van Uytfanghe Katleen , Vesper Hubert W , Zhang Tianjiao ,   for the JCTLM Task Force on Reference Measurement System Implementation
Published: September 2021

Background

The JCTLM created a Task Force on Reference Measurement System Implementation (TF-RMSI) to provide guidance on metrological traceability implementation for the in vitro diagnostics (IVD) community.

Content

TF-RMSI investigated the reference measurement systems (RMS) for 13 common measurands by applying the following procedural steps: (a) extracting data from the JCTLM database of available certified reference materials (CRMs) and reference measurement procedures (RMPs); (b) describing the RMS to which each recruited CRM or RMP belongs; (c) identifying the intended use of the CRMs, and, if used as a common calibrator for IVD measuring systems and/or trueness assessment of field methods was included, checking the CRM’s certificate for information about commutability with clinical samples; and (d) checking if the CRM or RMP measurement uncertainty (MU) has the potential to be small enough to avoid significantly affecting the analytical performance specifications (APS) for MU of clinical sample results when the MU from the IVD calibrator and from the end-user measuring system were combined.

We produced a synopsis of JCTLM-listed higher-order CRMs and RMPs for the selected measurands, including their main characteristics for implementing traceability and fulfilling (or not) the APS for suitable MU. Results showed that traceability to higher-order references can be established by IVD manufacturers within the defined APS for most of the 13 selected measurands. However, some measurands do not yet have suitable CRMs for use as common calibrators. For these measurands, splitting clinical samples with a laboratory performing the RMP may provide a practical alternative for establishing a calibration hierarchy.
Multiple Myeloma Minimal Residual Disease Detection: Targeted Mass Spectrometry in Blood vs Next-Generation Sequencing in Bone Marrow
Authors: Langerhorst Pieter , Noori Somayya , Zajec Marina , De Rijke Yolanda B , Gloerich Jolein , van Gool Alain J , Caillon Hélène , Joosten Irma , Luider Theo M , Corre Jill , VanDuijn Martijn M , Dejoie Thomas , Jacobs Joannes F M
Published: September 2021

Background

Minimal residual disease (MRD) status assessed on bone marrow aspirates is a major prognostic biomarker in multiple myeloma (MM). In this study we evaluated blood-based targeted mass spectrometry (MS-MRD) as a sensitive, minimally invasive alternative to measure MM disease activity.

Methods

Therapy response of 41 MM patients in the IFM-2009 clinical trial (NCT01191060) was assessed with MS-MRD on frozen sera and compared to routine state-of-the-art monoclonal protein (M-protein) diagnostics and next-generation sequencing (NGS-MRD) at 2 time points.

Results

In all 41 patients we were able to identify clonotypic M-protein-specific peptides and perform serum-based MS-MRD measurements. MS-MRD is significantly more sensitive to detect M-protein compared to either electrophoretic M-protein diagnostics or serum free light chain analysis. The concordance between NGS-MRD and MS-MRD status in 81 paired bone marrow/sera samples was 79%. The 50% progression-free survival (PFS) was identical (49 months) for patients who were either NGS-positive or MS-positive directly after maintenance treatment. The 50% PFS was 69 and 89 months for NGS-negative and MS-negative patients, respectively. The longest 50% PFS (96 months) was observed in patients who were MRD-negative for both methods. MS-MRD relapse during maintenance treatment was significantly correlated to poor PFS (P < 0.0001).

Conclusions

Our data indicate proof-of-principle that MS-MRD evaluation in blood is a feasible, patient friendly alternative to NGS-MRD assessed on bone marrow. Clinical validation of the prognostic value of MS-MRD and its complementary value in MRD-evaluation of patients with MM is warranted in an independent larger cohort.
The lampricide 3-trifluoromethyl-4-nitrophenol causes temporary metabolic disturbances in juvenile lake sturgeon (Acipenser fulvescens): implications for sea lamprey control and fish conservation
Authors: Ionescu R Adrian , Hepditch Scott L J , Wilkie Michael P
Published: September 2021

The pesticide 3-trifluoromethyl-4-nitrophenol (TFM) is applied to rivers and streams draining into the Laurentian Great Lakes to control populations of invasive sea lamprey (Petromyzon marinus), which are ongoing threats to fisheries during the lamprey’s hematophagous, parasitic juvenile life stage. While TFM targets larval sea lamprey during treatments, threatened populations of juvenile lake sturgeon (Acipenser fulvescens), particularly young-of-the-year (<100 mm in length), may be adversely affected by TFM when their habitats overlap with larval sea lamprey. Exposure to TFM causes marked reductions in tissue glycogen and high energy phosphagens in lamprey and rainbow trout (Oncorhynchus mykiss) by interfering with oxidative ATP production in the mitochondria. To test that environmentally relevant concentrations of TFM would similarly affect juvenile lake sturgeon, we exposed them to the larval sea lamprey minimum lethal concentration (9-h LC99.9), which mimicked concentrations of a typical lampricide application and quantified energy stores and metabolites in the carcass, liver and brain. Exposure to TFM reduced brain ATP, PCr and glycogen by 50–60%, while lactate increased by 45–50% at 6 and 9 h. A rapid and sustained depletion of liver glucose and glycogen of more than 50% was also observed, whereas the respective concentrations of ATP and glycogen were reduced by 60% and 80% after 9 h, along with higher lactate and a slight metabolic acidosis (~0.1 pH unit). We conclude that exposure to environmentally relevant concentrations of TFM causes metabolic disturbances in lake sturgeon that can lead to impaired physiological performance and, in some cases, mortality. Our observations support practices such as delaying TFM treatments to late summer/fall or using alternative TFM application strategies to mitigate non-target effects in waters where lake sturgeon are present. These actions would help to conserve this historically and culturally significant species in the Great Lakes.
Fearsome Worlds and Uncanny Children: Gothic Early Childhoods in Condé’sLa Migration des coeursand Kincaid’sThe Autobiography of My Mother
Authors: Manizza Roszak Suzanne
Published: September 2021

Gothic depictions of early childhood and its antecedents from conception to childbirth stand to fundamentally shape readers’ understanding of colonialism across the transnational and translinguistic space of the Caribbean. This effect is particularly visible in contemporary novels such as Maryse Condé’s La Migration des coeurs (1995) and Jamaica Kincaid’s The Autobiography of My Mother (1996), which not only have been interpreted as rewritings of Wuthering Heights but also draw on a larger, more multicultural Gothic literary tradition. In their renderings of sexual violence, doomed pregnancies, and motherless infancy, Condé and Kincaid appropriate and edit Gothic conventions, highlighting persisting ramifications of the colonial project for women and children. Gothic youth also functions as a subversive site of resistance with the potential to dismantle imperialist ideologies and systems.