bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Characterisation of Graves’ Disease-Specific Extracellular Vesicles from Tissue Maintained on a Bespoke Microfluidic Device
Authors: Green Victoria , Foster Hayley , Wade Mark , England James , Greenman John
Published: March 2022

Introduction

Inflammation, a characteristic of Graves’ disease, leads to opthalmopathy in 30–50% of Graves’ disease patients, and even blindness (5% of cases). Despite extensive research the pathogenesis of this disease remains unclear. This report demonstrates the maintenance of human Graves’ disease tissue ex vivo with subsequent isolation and characterisation of Graves’ disease specific exosomes.

Methods

Human tissue biopsies from Graves’ disease (n=11) and non-Graves’ disease (Hashimoto’s thyroiditis, n=3; follicular adenoma, n=1) were incubated in microfluidic devices for 6 days ± dexamethasone or methimazole, and effluent was analysed for size and concentration of extracellular vesicles (EV) using nanoparticle tracking. Exosomes isolated by ultracentrifugation were characterised using Western blotting and qRT-PCR for miRNA-146a and -155.

Results

Tissue specific EV were detected in all effluent samples. No consistent difference in EV concentration or size was observed in EV released from Graves’ compared to non-Graves’ disease tissue and no effect of treatment was evident. The exosome markers CD63 and CD81 were detectable in 2/5 Graves’ disease EV and CD63 was also evident in EV from a single non-Graves’ sample. miRNA-146a and -155 were detectable in all samples, with no difference between tissue cohorts. Treatment did not influence miRNA expression in EV from Graves’ disease tissue. Although miRNA-146a and -155 were elevated following treatment of non-Graves’ disease tissue with dexamethasone and methimazole, the increase was not significant, likely due to small sample size.

Conclusion

This preliminary study presents a unique method for isolation and characterisation of tissue specific EV for investigating disease pathogenesis and progression.
Management of iatrogenic parathyroid failure: beyond current BAETS guideline
Authors: Biswas Debabrata , Hardy Alistair , Shenoy Ashwini
Published: March 2022

Introduction

Hypocalcaemia is the most common post-operative complication of total thyroidectomy, in 23.5% of cases. The management of acute hypocalcaemia is well described, however there remains a lack of evidence for longer term management of these patients with ongoing parathyroid failure. We show how this could be predicted, prevented, and appropriately managed.

Method

We performed a systematic review of the literature regarding hypocalcaemia and parathyroid failure following total thyroidectomy.

Results

Risk factors for the development of hypocalcaemia include: female gender; lower age; Graves’ disease; level VI neck dissection; and poor surgical technique. Biochemical markers predict ongoing hypocalcaemia: calcium < 1.88mmol/L 24 hours after surgery is a significant risk; PTH ≥ 1.6pmol/L is a low risk. Combining calcium levels and PTH at 4 hours post-operatively helps significantly improve the predictive values and patients can be started on treatment as required. Day 5 post-operative repeat PTH and calcium monitors the need for medication. A key moment is 1 month following surgery, when two thirds of hypocalcaemic patients have recovered. Repeated blood tests at this point can help stopping or decreasing medical therapy.

Conclusions

This research work yields a structured approach to deal with persistent hypocalcaemia into four different categories. It may help discharging patients early from hospital after thyroidectomy and also may avoid long-term supplementation. Supplements can be stopped after one month with repeat calcium and parathyroid checks to recognise those who may require long-term treatment. Close communication between surgeons, endocrinologists, and patients is key.
Levothyroxine dosing post total thyroidectomy – the ideal equation?
Authors: Oh Soo , Rathod Sneha , Ross Elizabeth
Published: March 2022

Aims

Levothyroxine (LT4) therapy is necessary post total thyroidectomy to suppress TSH for differentiated thyroid cancer (DTC) and euthyroidism for benign thyroid disorders. We aim to evaluate the accuracy of empirical LT4 regimens alongside existing formulas in literature and identify predictive variables for LT4 dosage.

Methods

Retrospective study between January 2018 to February 2021 for all total thyroidectomies at UHNM. Total 50 cases identified from central database for each group (DTC vs benign). Data collected and analysed including patient demographics, diagnosis, LT4 regimens and thyroid function.

Results

Most patients were started empirically on 125mcg/day LT4 (92% vs 90%, DTC vs benign). This led to 78% of DTC group and 82% of benign group being within 25mcg of the final LT4 regimen. For DTC thyroidectomies, comparing 125mcg/day versus recommended 2mcg/kg had an average error of -9.1% versus +26.1%. Correlation between Body Mass Index (BMI), Lean Body Mass (LBM) or Body Surface Area (BSA) to final LT4 was weak to moderate (r=0.4 p=0.002, r=0.6 p=<0.001, r=0.6 p=<0.001).

For benign thyroidectomies, comparing 125mcg/day to BNF dose 1.6mcg/kg and formulas in literature resulted in average error ranging between -1.9% to +27.1%. The best average error was +0.2% using the formula 1.5mcg/kg by Jin et al. No correlation was found between BMI, LBM or BSA with final LT4 regimens (r=0.1 p=0.443, r=0.2 p=0.216, r=0.2 p=0.211).

Conclusion

In our subset, empirical dosing at 125mcg gives reasonable estimate of final LT4 dose. BMI, LBM or BSA alone was not a consistent predictor for final LT4 dose. Further validation of predictive formulas is needed.
Safety of Daycase Thyroid and Parathyroid Surgery with Developments in Education and Training in addition to Patient Information Leaflets.
Authors: Wilson Denise , Raistrick Maria , Houghton Neil , Tomlinson Mark , Walls Gerard
Published: March 2022

Introduction

BAETS recently reviewed daycase thyroid surgery in the UK through a debate and webinar; and changed the society's position statement in support of daycase thyroid procedures. Post-thyroidectomy haemorrhage remains a concern. This Endocrine Surgical Unit published data (2015 & 2017) regarding our daycase thyroid/parathyroid surgery since 2005. The practice has developed in numbers, patient information given and safety protocols.

Method

We reviewed our outcomes from the last 4 years and developed a Patient Information Leaflet that reflects the new BAETS position, outlining what to expect from surgery, what to look out for in the post-operative period, and what action to take should complications arise. This is used in conjunction with our stringent protocol for daycase thyroid/parathyroid surgery (exclusion criteria include: children; bilateral/redo surgery; sternotomy; ASA 3&4; living alone; >45 minutes from hospital).

Results

Review of cases performed between June 2017 and May 2021 confirmed 25.2% (81/322) of procedures were daycase and without complication (28 (all lobectomies)/160 thyroid and 53/162 parathyroid procedures, respectively). Protocol improvements include an ‘emergency pack’ of wound-opening equipment staying with the patient throughout their stay; training for Ward and Emergency Department staff in opening neck incisions for postoperative haemorrhage (SCOOP video, posters displayed in ward areas and within the emergency pack, provision of instruments within the Emergency Department).

Conclusion

Outcomes demonstrate safety of daycase thyroid and parathyroid surgery in a UK hospital within our protocol. Refinements to our protocol, staff education, instrument availability and patient information leaflets aim to ameliorate concerns about daycase thyroid/parathyroid surgery for patients and staff.
An audit of MEN-1 screening in a large tertiary endocrine surgery centre – A single centre experience
Authors: Jaafar Mustafa , Anneback Matilda , Di Marco Aimee , Palazzo Fausto , Tolley Neil
Published: March 2022

Introduction

Multiple endocrine neoplasia (MEN-1) usually presents following a diagnosis of primary hyperparathyroidism (PHPT). U.K. practice guidelines advise screening patients less than age 30 to identify MEN-1 mutations. It is our departmental policy to screen all patients under the age of 40.

Methods

A retrospective review of all patients having parathyroidectomy under the age of 40. A review of their mutational analysis and yield were the audit parameters.

Results

The records of 53 patients (17 F, 36 M) were available for audit (incomplete records were excluded); 45 patients had MEN-1 mutational analysis. 8 patients were not screened and 31% (14/45) were positive for MEN-1 mutations, 1 patient was positive for CDC73.

Conclusion

An 85% rate of compliance with the departmental screening protocol was found. This compares with a 25% yield in Uppsala and 11% in Utrecht.
Attitudes of general surgical trainees towards endocrine surgery
Authors: Vance-Daniel Joseph , Jamal Karim
Published: March 2022

Introduction

Endocrine surgery is currently recognised by all surgical colleges in the UK as a subspecialty within general surgery. However, subjectively there appear to be very few trainees with an interest in pursuing a career in endocrine surgery. This study aims to assess the attitudes of trainees towards the subspecialty, as well as identifying possible barriers.

Methods

An online questionnaire was designed and sent to surgical trainees working in different hospitals throughout the London, to be completed anonymously.

Results

31 trainees responded - 30 who were currently in training, and 1 post CCT.

Only 1 (3.2%) wanted to pursue a career in endocrine surgery with 67.7% stating that they had not considered a career in endocrine surgery. 38.7% had no experience working in endocrine surgery. The most common deterrents to pursuing a career in endocrine surgery were:

Conclusion

Low numbers of trainees have considered or are pursuing a career in endocrine surgery. Lack of exposure, a shortfall within the curriculum and other perceived barriers play the largest role in deterring trainees. These factors could be resolved through increasing exposure and education, as well as focusing on the factors which trainees find most appealing.
Can we justify using Parathyroid Ultrasound Scan as a sole preoperative localisation study for patients undergoing surgery for Primary Hyperparathyroidism?
Authors: Acharya Ravi , Kopczynska Maja , Ghattamaneni Sunethra , Doran Helen
Published: March 2022

Introduction

Currently we offer unilateral neck exploration parathyroidectomy (UNE-PTX) only to patients with concordant ultrasound (USS) and nuclear medicine (NM) scans.

Objective

To compare potential cure rate from UNE-PTX to any patient with a single gland identified on USS with the current practice of dual concordant scans.

Methods

Case ascertainment; patients undergoing successful parathyroidectomy 2008 to 2018 by a single surgeon. Electronic patient records reviewed for imaging, operative records and pathology.

Results

331 patients underwent surgery, 325 (98.2%) were cured. 288 (88.6%) had a single adenoma (PA), 37 (11.4%) had multi-gland disease (MGD)

All patient had either USS or NM. 320 underwent US & 315 NM scans. 309 patients had dual imaging.

Sensitivity and specificity respectively were 72.3% & 60.5% for US and 65.8% & 62.2% for NM scans.

USS accuracy was not influenced by the radiologist having prior access to NM report (kappa 0.4 vs 0.44).

Concordant imaging; 141 patients. Of these 135 had a confirmed PA. 127 underwent UNE-PTX, 14 required bilateral neck exploration (BNE).

US localised single gland; 217 patients. Of these 51(20.6%) had no uptake on NM scans.

Based on US localisation alone if all 217 were offered UNE-PTX, 205/217 (94.5%) of patients with adenoma would be cured; 12 /217 (4.5%) with MGD recognisable at operation would have to be converted to BNE.

Conclusion

In our patients with a single adenoma using USS alone would have avoided 20.6% unnecessary BNE This has financial benefits to the health service as it avoids another investigation and hospital visit.
Malignancy rates and initial management of Thy3 thyroid nodules in a district general hospital: The ‘Reading’ experience
Authors: Maweni Robert , Nair Dilip , Kandiah Shivanthi , Rourke Thomas , Corbridge Rogan , Nagala Sidhartha
Published: March 2022

Introduction

Ultrasound-guided fine-needle aspiration cytology is the gold standard for investigating thyroid nodules. Stratifying the Thy3 thyroid nodule risk of malignancy is essential for clinical decision-making. According to the Royal College of Pathologists Guidance (2016), the rate of malignancy for Thy3a is 5–15% and for Thy3f 15–30%. Our aim was to investigate the malignancy rate and the initial management of Thy3 nodules in our institution.

Methods

A retrospective review was undertaken of 115 patients with Thy3 cytology results from thyroid fine-needle aspirations performed between January 2015 and June 2020 at a single centre. A total of 90 out of 115 patients underwent surgery.

Results

Of the 90 patients, we had a 40% malignant rate (36/90). Specifically, 14 of 34 (41.1%) Thy3a and 22 of 56 (39.2%) Thy3f nodules were malignant. Of the malignant lesions, 52.7% (19/36) were follicular thyroid carcinoma. 58.8% (10/17) of male patients and 35.6% (26/73) of female patients had a malignant histology. Eighteen patients eventually needed a completion thyroidectomy.

Conclusion

Compared with national data, we showed a higher risk of malignancy in Thy3 nodules in our centre. Our study should encourage other centres to audit their own data. We propose setting up a national Thy3 registry as a basis to promote research in improving preoperative diagnosis of indeterminate thyroid nodules.
Clinical Efficacy And Cure Rate Of Fixed Dose Radioactive Iodine For The Treatment Of Hyperthyroidism: A Single Centre Study
Authors: Maweni Robert , Nair Dilip , Constatinou Christoforos , Kandiah Shivanti , Aung Theingi , Nagala Sidhartha
Published: March 2022

Introduction

Iodine-131 is an effective treatment for thyrotoxicosis. In 2019, the National Institute for Clinical Excellence (NICE) guidelines suggested offering radioactive iodine as first-line definitive treatment for adults with Graves’ disease, toxic nodular and multinodular goitre unless it is unsuitable or anti-thyroid drugs are likely to achieve remission. The aim of this study was to evaluate the clinical outcome one year after using fixed dose Iodine-131 for hyperthyroidism and to identify any associated factors.

Methods

Electronic patient records were studied retrospectively for all patients who were treated with radioiodine therapy for hyperthyroidism between July 2017 and March 2020 at a district general hospital in the UK. Response to radioiodine therapy was assessed at 6 and 12 months by a dedicated thyroid nurse-led virtual follow-up.

Results

We identified 67 patients with a mean age of 55.9 years (range 18–84); 48 (72%) females, 19 (28%) males. Of these, 57 (85%) patients were cured at 12 months (93.7% in non-Graves’, 82.3% in Graves’ group). Gender, diagnosis, and pre-treatment disease interval were not significantly associated with treatment success. Non-Graves’ patients had a significantly shorter time to discharge than Graves’ patients receiving Iodine-131 (8 vs 10.3 months, p=0.0174).

Conclusions

The results of the present study demonstrate that a single fixed dose of Iodine-131 therapy is highly effective and comparable to outcomes from calculated dose therapy in literature. We propose the routine use of scoring system to calculate risk of relapse for all newly diagnosed hyperthyroid patients to tailor treatment modality.
New, simple, fast, whole blood Intraoperative PTH assay – Laboratory and Clinical validation
Authors: Kurzawinski Tom , Soromani Christina , Aziz Tarek Abdel , Lam Francis , Garcia Virginia Rozalen , Matias Michele , Morley sujiwa , Barth Julian
Published: March 2022

Introduction

IOPTH monitoring is a reliable method of predicting cure during the surgery for Primary Hyperparathyroidism (PHPT) but current methods are slow and require presence of laboratory staff. NBCL Connect is the first Analyser which can be used by theatre staff and measures whole blood PTH in 5 minutes.

Aim

Laboratory and Clinical validation of new IOPTH assay in patients undergoing surgery for PHPT.

Methods

Intra and inter assay variability using BioRad Liquichek Specialty Immunoassay, internal quality controls and serum and whole blood PTH concentrations in patients cured by parathyroidectomy for PHPT measured on NBCL and “gold standard” Future Diagnostics (FD) and Roche platforms. Pearson coefficient was used for linear correlation between measurements.

Results

Preliminary precision data confirms good analytical performance of NBCL Analyser which is similar to that of FD platform. Further precision, accuracy, linearity and sensitivity studies are ongoing.

Plasma PTH concentration from 4 patients (5 samples each, total 20) measured on NBCL and FD platforms showed good correlation (R 0.90, slope 0.644, IC – 0.68)

Whole blood PTH concentration in 2 patients (5 samples each, total 10) measured on NBCL, FD and Roche platforms showed good correlation. 50% reduction in circulating PTH, main (Miami) criteria confirming biochemical cure, were similar for all 3 platforms

Conclusions

NBCL Connect Analyser assay showed good laboratory and clinical performance able to predict biochemical cure in patients undergoing surgery for PHPT. Our preliminary data suggests that this straightforward to operate and fast system is a promising technology which can be used widely during parathyroid surgery.
Morbidity after thyroid surgery in children: patient perspective
Authors: Patel Neil , Johnson Paul , Mihai Radu
Published: March 2022

Aim

To explore the children’s/parents’ perception of morbidity after thyroid surgery.

Methods

Retrospective analysis of consecutive unselected patients who had undergone a thyroid operation under joint care of Paediatric and Endocrine surgeons. Electronic patients records were used to obtain relevant information and a standardised questionnaire was mailed to all children.

Results

Between Jan2009- Dec2020 62 children age 2–18 (median 15.2) had thyroid lobectomy (n=27) or total thyroidectomy (n=35). In-hospital stay ranged 1–3 days (mode1).

Replies were received from 20 children at a median 37 months (range 5–60 months) after lobectomy (n= 8) or total thyroidectomy (n=12). Subjective voice assessment using a visual analogue scale remained normal in all children. Voice handicap index scores were normal in 13 (65%) children and increased in 7 (35%) to a median of 4 (range 1–10). Voice-related quality of life was excellent in 18 (90%) children and very good in two children. Swallowing was normal in 14 children, moderately affected in four children and severely affected in 2 children. Appearance of the scar assessed using the Manchester score ranged from 5–16, median 9, with only one child with an ideal score of 5. Three children have had or are waiting for scar revision. There was no persistent hypoparathyroidism.

Conclusion

In this cohort of children undergoing thyroid surgery, there were no significant voice changes and swallowing morbidity was infrequent. Concerns related to scar appearance were far more common than in the adult population and this should be highlighted in the consent process.
Quality outcomes comparison of total thyroidectomy between UKRETS and HES databases
Authors: Rajan Sendhil , Aspinall Sebastian , Gray William , Day Jamie , Lansdown Mark , Tolley Neil
Published: March 2022

Aims

Hospital Episodes Statistics for England (HES) and UK Registry of Endocrine and Thyroid Surgery (UKRETS) are the largest databases on thyroidectomy within the UK. A validation of UKRETS data accuracy has never occurred. The purpose of this study was to compare quality outcomes in total thyroidectomy (TT) between the UKRETS and HES datasets.

Methods

A retrospective comparison study between UKRETS and HES for TT from April 2012–March 2018. Vocal cord palsy, hypocalcaemia, mortality & length of stay were the quality outcomes studied.

Results

The HES and UKRETS databases contained 23,025 and 11,242 patients respectively with UKRETS capturing 48.8% of HES data for TT. 18.8%(42/223) of surgeons performed ≥20 procedures/year in 54.3%(6110/11,242) of UKRETS procedures compared to only 9.7%(72/740) of surgeons from HES performing 44.6%(10,279/23,035) of all TTs. Median length of stay was significantly higher within in HES(2 days, IQR 1-3) versus UKRETS(1 day, IQR 1-2). 30.7%(7,071) of HES patients stayed for >2 days compared to 18.7%(1,837) within the UKRETS registry. Both databases reported a mortality of 0.1%. Post-operative hypocalcaemia was reported higher in UKRETS (21.7%) compared to HES (6.8%), p<0.0001. Rates of voice change were significantly higher in UKRETS (9.4%) compared to those in HES (1.3%), p<0.0001.

Conclusions

Surgeons contributing to UKRETS had a higher volume practice and shorter stay than those within HES. UKRETS appears to underreport the number of procedures conducted, with less low volume surgery captured. However, recording of hypocalcaemia and voice changes is mandatory in UKRETS, and HES appear to substantially under-report such complications.
The Rise of Twiplomacy and the Making of Customary International Law on Social Media
Authors: Green James A
Published: February 2022

Social media usage by States has increased exponentially in recent years. This phenomenon, known as “twiplomacy”, has become ubiquitous. Given that almost every State in the world now issues statements via social media, this article examines the potential for Twitter posts to form part of the “raw material” for the formation of customary international law. In other words, it considers whether customary international law can be “made”, or evidence of it identified, on social media. Public statements can, in the right contexts, act as State practice or as evidence of opinio juris, and a Twitter post from a State account ultimately is a public statement like any other. Based on an original scoping study, it is argued that there is evidence of statements being posted on Twitter that, were they issued in a more traditional context, would be seen as having the potential to constitute State practice or evidence of opinio juris. The study also suggests that such examples are not yet common, but it is predicted that they will become so. Therefore, this article goes on to examine a number of possible implications of twiplomacy for the identification of customary international law that must be considered, should social media indeed emerge as a notable breeding ground for new rules of custom. These implications include the blurring between the “personal” and the “official”; the brevity and (lack of) clarity and rigour of tweets; the significant increase in the amount of relevant data but also its comparative “centralisation” (with potentially positive as well as negative consequences); and concerns regarding authenticity. It ultimately is concluded that twiplomacy will not change the requirements for the formation of customary international law, but it is likely to have significant implications for how lawyers and researchers go about the practical process of identifying it.
When Do Established Powers Support Rising Powers’ Multilateral Institutions? The Case of the Asian Development Bank
Authors: Kaya Ayse , Salah Matthew
Published: February 2022

What are the institutional features that incentivize established powers to join rising powers’ new institutions? Going beyond alliance versus rivalry, this paper develops a novel theory in answering this question. We argue that the established power must address two primary design issues: 1. how to navigate the control and burden-sharing trade-off and 2. how to limit the potential diffusion of power by rendering the new institution “complementary” to the existing order. To the extent that these issues are resolved in line with the established power’s (EP’s) preferences, the EP is more likely to join the rising powers’ institutions. We support our theory with an in-depth case analysis of the Japanese-led Asian Development Bank, utilizing primarily archival materials. The relatively under-theorized core question has both historical and contemporary relevance. The paper also advances the history of US multilateral economic policy.
Seasonal resource selection of an arboreal habitat specialist in a human-dominated landscape: A case study using red panda
Authors: Bista Damber , Baxter Greg S , Hudson Nicholas J , Murray Peter J
Published: February 2022

Human-dominated landscapes provide heterogeneous wildlife habitat. Conservation of habitat specialists, like red pandas Ailurus fulgens, inhabiting such landscapes is challenging. Therefore, information on resource use across spatial and temporal scales could enable informed-decision making with better conservation outcomes. We aimed to examine the effect of geo-physical, vegetation, and disturbance variables on fine-scale habitat selection of red pandas in one such landscape. We equipped 10 red pandas with GPS collars in eastern Nepal in 2019 and monitored them for 1 year. Our analysis was based on a generalized-linear-mixed model. We found the combined effect of geo-physical, vegetation, and disturbance variables resulted in differences in resource selection of red pandas and that the degree of response to these variables varied across seasons. Human disturbances, especially road and cattle herding activities, affected habitat utilization throughout the year whereas other variables were important only during restricted periods. For instance, geo-physical variables were influential in the premating and cub-rearing seasons while vegetation variables were important in all seasons other than premating. Red pandas selected steeper slopes with high solar insolation in the premating season while they occupied elevated areas and preferred specific aspects in the cub-rearing season. Furthermore, the utilized areas had tall bamboo in the birthing and cub-rearing seasons while they also preferred diverse tree species and high shrub cover in the latter. Our study demonstrates the significance of season-specific management, suggests the importance of specific types of vegetation during biologically crucial periods, and emphasizes the necessity to minimize disturbances throughout the year.
Peripheral bare-metal stent implantation for a very-late stenosis of an aortic-left main Cabrol graft: a case report
Authors: Carrera Arcangelo , Contorni Francesco , Gambacciani Andrea , Neri Eugenio
Published: February 2022

Background

The surgical ascending aorta repair according to the Cabrol procedure involves the interposition of a prosthetic conduit between the aortic prosthesis and the native coronary ostia. Previous cases of the Cabrol conduit stenosis have been described, most of which presented as acute coronary syndromes due to thrombotic occlusion of the graft.

Case summary

We present a case of stable exertional angina due to very-late stenosis of the coronary prosthetic conduit, successfully treated with trans-femoral percutaneous angioplasty and off-label implantation of a balloon-expandable bare-metal stent designed for peripheral artery disease. The multimodality imaging approach gave an essential contribution both to the assessment of the lesion and to the procedural planning. Despite the concerns about long-term results, a peripheral bare-metal stent was preferred over a standard coronary drug-eluting stent due to the remarkable dimension of the Cabrol conduit. Three years after the procedure, the patient is free from angina, and coronary computed tomography showed no significative luminal loss of the stent.

Conclusion

Elective angioplasty of a Cabrol graft requires a careful planning through a multimodality stenosis assessment. Conventional coronary stents can be not large enough to ensure adequate apposition to the wide prosthetic conduit and peripheral bare-metal stents may be taken into consideration, at the price of unknown long-term outcomes.
The Treaty of Nîmes (1704): fake news, propaganda and diplomacy during the War of the Spanish Succession
Authors: Laborie Lionel
Published: March 2022

This article reappraises the significance of the ‘Treaty of Nîmes’, a fake historical document that supposedly ended the War of the Cévennes in May 1704. The agreement was negotiated by Camisard leader Jean Cavalier and Louis XIV’s representative in Languedoc, the Maréchal de Villars. It claimed no less than to restore the Edict of Nantes in Languedoc two decades after its revocation, and sparked speculation among the Protestant coalition about the true state of French domestic affairs in the midst of the War of the Spanish Succession. Dissecting its individual articles against the backdrop of contemporary correspondences, newspapers and pamphlets, this article thus reconstructs the origins and true purpose of that controversial agreement to show the limits of the Sun King’s absolutist rule, and makes a case more generally for the historical value of fake historical documents.
Genome size evolution in the diverse insect order Trichoptera
Authors: Heckenhauer Jacqueline , Frandsen Paul B , Sproul John S , Li Zheng , Paule Juraj , Larracuente Amanda M , Maughan Peter J , Barker Michael S , Schneider Julio V , Stewart Russell J , Pauls Steffen U
Published: February 2022

Background

Genome size is implicated in the form, function, and ecological success of a species. Two principally different mechanisms are proposed as major drivers of eukaryotic genome evolution and diversity: polyploidy (i.e., whole-genome duplication) or smaller duplication events and bursts in the activity of repetitive elements. Here, we generated de novo genome assemblies of 17 caddisflies covering all major lineages of Trichoptera. Using these and previously sequenced genomes, we use caddisflies as a model for understanding genome size evolution in diverse insect lineages.

Results

We detect a ∼14-fold variation in genome size across the order Trichoptera. We find strong evidence that repetitive element expansions, particularly those of transposable elements (TEs), are important drivers of large caddisfly genome sizes. Using an innovative method to examine TEs associated with universal single-copy orthologs (i.e., BUSCO genes), we find that TE expansions have a major impact on protein-coding gene regions, with TE-gene associations showing a linear relationship with increasing genome size. Intriguingly, we find that expanded genomes preferentially evolved in caddisfly clades with a higher ecological diversity (i.e., various feeding modes, diversification in variable, less stable environments).

Conclusion

Our findings provide a platform to test hypotheses about the potential evolutionary roles of TE activity and TE-gene associations, particularly in groups with high species, ecological, and functional diversities.
Can a high-powered financial incentive programme reduce resignation rates among healthcare providers in rural areas? Evidence from Thailand’s 2008 Hardship Allowance programme
Authors: Noochpoung Rakchanok , Hung Peiyin , Hair Nicole L , Putthasri Weerasak , Chen Brian
Published: March 2022

Geographic disparities in the availability of healthcare providers remain a global health challenge. Financial incentives have been widely implemented to attract rural healthcare workers with limited scientific evidence in developing economies. In this study, we investigate the relationship between financial incentives and rural resignations in a middle-income country using Thailand’s Hardship Allowance programme that first doubled or tripled but later decreased direct payments to rural providers. This retrospective observational study used data on dentists’ work status from the Human Resource Management Department at the Ministry of Public Health in Thailand. Segmented regression and difference-in-differences approaches were used to analyse the effect of changes to the Hardship Allowance on rural dentists’ resignation and relocation patterns. We found that the dramatic increase in the Hardship Allowance in 2008 was associated with a decrease in resignation rates among dentists in rural areas. However, after Thailand recategorized certain rural districts into urban areas in 2016, dentists were more likely to relocate from the newly urbanized areas to established urban centres, likely due in part to reductions in the Hardship Allowance that accompanied recategorization. However, we did not find that resignations increased in these affected areas. Finally, in a subgroup analysis, we found that older dentists were less likely than younger dentists to relocate from areas affected by the 2016 rural-to-urban recategorization. Overall, our study found that a dramatic increase in financial incentives reduced resignation rates in rural Thailand, but a reversal of the incentives as a result of rural-to-urban reclassification resulted in relocations from the affected areas to established urban centres. When considering their strategic goals of equitable healthcare workforce distribution, policymakers should be aware that both direct and indirect changes to payment incentives may affect dentists’ resignation and practice location decisions and that these decisions may be influenced by provider demographics.
Perceptions of the health risks of cannabis: estimates from national surveys in Canada and the United States, 2018–2019
Authors: Goodman Samantha , Hammond David
Published: March 2022

Few studies have compared knowledge of the specific health risks of cannabis across jurisdictions. This study aimed to examine perceptions of the health risks of cannabis in Canada and US states with and without legal non-medical cannabis. Cross-sectional data were collected from the 2018 and 2019 International Cannabis Policy Study online surveys. Respondents aged 16–65 (n = 72 459) were recruited from Nielsen panels using non-probability methods. Respondents completed questions on nine health effects of cannabis (including two ‘false’ control items). Socio-demographic data were collected. Regression models tested differences in outcomes between jurisdictions and by frequency of cannabis use, adjusting for socio-demographic factors. Across jurisdictions, agreement with statements on the health risks of cannabis was highest for questions on driving after cannabis use (66–80%), use during pregnancy/breastfeeding (61–71%) and addiction (51–62%) and lowest for risk of psychosis and schizophrenia (23–37%). Additionally, 12–18% and 6–7% of respondents agreed with the ‘false’ assertions that cannabis could cure/prevent cancer and cause diabetes, respectively. Health knowledge was highest among Canadian respondents, followed by US states that had legalized non-medical cannabis and lowest in states that had not legalized non-medical cannabis (P < 0.001). Overall, the findings demonstrate a substantial deficit in knowledge of the health risks of cannabis, particularly among frequent consumers.
IVF and human evolution
Authors: Hanevik Hans Ivar , Hessen Dag O
Published: March 2022

Humans are shaped by evolution through natural selection, as are all species. While evolution is central to all biological processes, the key stage for competition and selection is reproduction, which encompasses various events from courtship and mating to fertilization and pregnancy. In humans, IVF is used to aid the intrinsically inefficient reproduction by coitus, and in several countries, the proportion of children born after IVF is increasing. While IVF is an enabling technology for infertile patients, it also circumvents reproductive barriers and changes selection pressures. This grand theme review describes the systematic differences between IVF and coitus in selection pressures on reproducing cells, individuals and populations. At the cellular unit of selection, for example, IVF favours different traits in spermatozoa (fast swimmers over short distances) than coitus does (forward mobility over longer distances). Similarly, a male with low sperm quality and a female who decides to delay her first birth to an advanced age, can both increase their reproductive fitness by IVF compared to if reproduction by coitus is their only option. In as much as delayed reproduction is a cultural trait, IVF thus enables cultural practices that may in their turn affect human evolution. A main point in this review is to discuss the interactive effects of biological and cultural traits in the context of IVF, and how they act in concert as drivers towards increased demand for IVF. It is not the aim of this review to argue against IVF, which no doubt is a major medical advancement, but rather to examine IVF and human evolution from a broad perspective, including potential longer-term impacts. Since IVF is a young technology, the empirical data indicative of evolutionary effects of IVF in humans are sparse. In general, we argue that IVF facilitates the redirection of resources away from reproduction in humans, since reproduction by IVF bypasses some of the resource-demanding processes that reproduction by coitus entails. Hence, IVF sets the evolutionary stage for a human species increasingly reliant on, and adapted to, technological means of reproduction.
Prophylactic (R,S)-Ketamine Is Effective Against Stress-Induced Behaviors in Adolescent but Not Aged Mice
Authors: Mastrodonato Alessia , Pavlova Ina , Kee Noelle C , Pham Van Anh , McGowan Josephine C , Mann J John , Denny Christine A
Published: February 2022

Background

(R,S)-ketamine, an N-methyl-D-aspartate receptor antagonist, is frequently used as an anesthetic and as a rapid-acting antidepressant. We and others have reported that (R,S)-ketamine is prophylactic against stress in adult mice but have yet to test its efficacy in adolescent or aged populations.

Methods

Here, we administered saline or (R,S)-ketamine as a prophylactic at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes 1 week before a 3-shock contextual fear-conditioning (CFC) stressor. Following CFC, we assessed behavioral despair, avoidance, perseverative behavior, locomotion, and contextual fear discrimination. To assess whether the prophylactic effect could persist into adulthood, adolescent mice were injected with saline or varying doses of (R,S)-ketamine and administered a 3-shock CFC as a stressor 1 month later. Mice were then re-exposed to the aversive context 5 days later and administered behavioral tests as aforementioned. Brains were also processed to quantify Cyclooxygenase 2 expression as a proxy for inflammation to determine whether the prophylactic effects of (R,S)-ketamine were partially due to changes in brain inflammation.

Results

Our data indicate that (R,S)-ketamine is prophylactic at sex-specific doses in adolescent but not aged mice. (R,S)-ketamine attenuated learned fear and perseverative behavior in females, reduced behavioral despair in males, and facilitated contextual fear discrimination in both sexes. (R,S)-ketamine reduced Cyclooxygenase 2 expression specifically in ventral Cornu Ammonis region 3 of male mice.

Conclusions

These findings demonstrate that prophylactic (R,S)-ketamine efficacy is sex, dose, and age dependent and will inform future studies investigating (R,S)-ketamine efficacy across the lifespan.
Accelerated exponential Euler scheme for stochastic heat equation: convergence rate of the density
Authors: Chen Chuchu , Cui Jianbo , Hong Jialin , Sheng Derui
Published: February 2022

This paper studies the numerical approximation of the density of the stochastic heat equation driven by space-time white noise via the accelerated exponential Euler scheme. The existence and smoothness of the density of the numerical solution are proved by means of Malliavin calculus. Based on a priori estimates of the numerical solution we present a test-function-independent weak convergence analysis, which is crucial to show the convergence of the density. The convergence order of the density in uniform convergence topology is shown to be exactly $1/2$ in the nonlinear drift case and nearly $1$ in the affine drift case. As far as we know, this is the first result on the existence and convergence of density of the numerical solution to the stochastic partial differential equation.
On Strongly Inflexible Manifolds
Authors: Costoya Cristina , Muñoz Vicente , Viruel Antonio
Published: February 2022

An oriented closed connected $N$-manifold $M$ is inflexible if it does not admit self-maps of unbounded degree. In addition, if all the maps from any other oriented closed connected $N$-manifold have bounded degree, then $M$ is said to be strongly inflexible. The existence of simply-connected inflexible manifolds was established by Arkowitz and Lupton. However, the existence of simply-connected strongly inflexible manifolds is still an open question. We provide an algorithm relying on Sullivan models that allows us to prove that all, but one, of the known examples of simply-connected inflexible manifolds are not strongly inflexible.
Burn Shock and Resuscitation: Review and State of the Science
Authors: Cartotto Robert , Burmeister David M , Kubasiak John C
Published: February 2022

Burn shock and acute fluid resuscitation continue to spark intense interest and debate among burn clinicians. Following a major burn injury, fluid resuscitation of burn shock is life-saving, but paradoxically can also be a source of increased morbidity and mortality because of the unintended consequence of systemic edema formation. Considerable research over the past two decades has been devoted to understanding the mechanisms of edema formation, and to develop strategies to curb resuscitation fluids and limit edema development. Recognition of burn endotheliopathy—injury to the endothelium’s glycocalyx layer—is one of the most important recent developments in our understanding of burn shock pathophysiology. Newer monitoring approaches and resuscitation endpoints, along with alternative resuscitation strategies to crystalloids alone, such as administration of albumin, or plasma, or high-dose ascorbic acid, have had mixed results in limiting fluid creep. Clear demonstration of improvements in outcomes with all of these approaches remains elusive. This comprehensive review article on burn shock and acute resuscitation accompanies the American Burn Association’s State of the Science meeting held in New Orleans, LA on November 2 to 3, 2021 and the Proceedings of that conference published in this journal.
A Randomized Controlled Pilot Study of Topical Ropivacaine for Prevention of Post-POEM Pain
Authors: Rai Mandip , Nazarin Amir , Taylor Connie , McMullen Michael , Hookey Lawrence , Chung Wiley , Bechara Robert
Published: February 2022

Background and Aims

Although usually mild to moderate in severity, postoperative pain after peroral endoscopic myotomy (POEM) is common. There are no studies that have addressed minimizing postoperative pain in patients undergoing POEM for achalasia. We hypothesized that intraoperative topical intra-tunnel irrigation with ropivacaine would result in a significant reduction in pain scores in the postoperative period.

Methods

A double-blind, randomized, placebo-controlled trial was conducted at the Kingston Health Sciences Center. Patients received either 30 mL of 0.2% ropivacaine or 30 mL of placebo irrigated topically into the POEM tunnel after completing the myotomy and prior to closing the mucosal incision. The primary outcome was pain post-POEM at 6 h assessed by the Numeric Rating Scale (NRS). Secondary objectives included assessing pain score at 0.5, 1, 2, 4 h post-POEM and on discharge, Quality of Recovery (QoR-15) scores at discharge, narcotic requirement, adverse events, and patients’ willingness to have the procedure done on an outpatient basis.

Results

A total of 20 patients were enrolled. For the primary outcome of pain post-POEM at 6 h, the NRS was 1.1 in the placebo group and 2.4 in the ropivacaine group (95% CI of the difference: −3.2 to 0.6, P = 0.171). No statistical difference was seen in the pain scores. Overall usage of post-procedural narcotics was low with no differences between the two groups. Fifty percent of patients in both groups were willing to have the procedure done as an outpatient.

Conclusion

The addition of intra-procedural tunnel irrigation with 30 mL 0.2% ropivacaine did not lead to reduced post-POEM pain.
Molecular Identification and Virulence of Four Strains of Entomopathogenic Fungi Against the Whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Lu Qian , Wang Peng , Ali Asad , Zang Lian-Sheng
Published: February 2022

The whitefly, Bemisia tabaci (Gennadius), is a key pest of many economically important crops grown in the field and in greenhouses throughout the world. Because entomopathogenic fungi (EPF) are potential biological control agents for B. tabaci, however, minimal research has been conducted on using fungal strains to control B. tabaci. In this study, four EPF strains were isolated and identified as Lecanicillium attenuatum (Zare & Gams) JL-003, Beauveria bassiana Balsamo (Vuillemin) JL-005, Lecanicillium longisporum (Petch) JL-006, and Akanthomyces lecanii (Zimmerman) JL-007, based on rDNA-ITS sequence analysis. In comparing the virulence of the four fungi against the different life stages (i.e., eggs, 1st-, 2nd-, 3rd-, 4th-instar nymphs, and adults) of B. tabaci the mortality of B. tabaci decreased and LT50 values increased as the conidia concentration decreased in a series of conidia concentrations (1 × 105, 106, 107, and 108 conidia/mL). The fungal strains L. attenuatum JL-003 (LC50: 1.31 × 106) and B. bassiana JL-005 (LC50: 0.92 × 106) were found to be more effective than L. longisporum JL-006 (LC50: 4.97 × 107) and A. lecanii JL-007 (LC50: 6.46 × 106). Fourth-instar nymphs, eggs, and adult stages of B. tabaci were less susceptible to all fungal strains compared to 1st-, 2nd-, and 3rd-instar nymphs. The virulence of L. attenuatum, which was tested for the first time on B. tabaci, was found to be more toxic to early-stage nymphs. Our data will be useful in biological control programs that are considering using EPF against B. tabaci.
T. J. Alldridge’s Sierra Leone collections
Authors: Hart William
Published: March 2022

Through his books, The Sherbro and its Hinterland (1901) and Sierra Leone: A transformed colony (1911), and his collections of ethnographic material from southern Sierra Leone, Thomas Joshua Alldridge (1847–1916) has probably had a greater influence in shaping the wider world’s perception of Sierra Leone’s traditional culture than any other single individual. The present article traces the history of his collections, showing that they were more extensive than is generally recognized, and documenting their dispersal to public institutions and private collectors in Europe and America. Among the questions it raises is how far the objects in Alldridge’s collections are an authentic representation of the ways of life of the peoples of southern Sierra Leone on the eve of colonization.
The International Criminal Justice Marketplace of Ideas
Authors: Christensen Mikkel Jarle , Godzimirska Zuzanna , Jarland Julie
Published: March 2022

The field of international criminal justice is supported and legitimized by a distinct marketplace of norms and ideas. Within this marketplace, stakeholders compete to define dominant norms, conceptual frames and the practical direction of international criminal justice. Building on the relational sociology of Bourdieu, this article examines how this competition plays out by studying the relational agenda-setting practices of central stakeholders. To this end, the analysis draws on an original dataset of annual reports produced by international criminal tribunals, academic articles and non-governmental organization reports published between 1994 and 2018. Employing Structural Topic Modelling, the article contributes a data-driven and empirically informed analysis of core developments and agenda-setting in the marketplace of ideas in international criminal justice. Zooming in on the topic of sexual violence which was placed on the agenda by NGOs in the early 2000s before becoming prevalent in the outputs of academics and international criminal tribunals, the article illustrates how normative agendas spearheaded by specific stakeholders can have broader effects in the field.