bluuebunny/crossref_metadata_2025 huggingface dataset:
Discontinuation of chronic benzodiazepine use in primary care: a nonrandomized intervention
Authors: Fernandes Milene , Neves Inês , Oliveira Joana , Santos Osvaldo , Aguiar Pedro , Atalaia Paula , Matos Fátima , Freitas Maria Carina , Alvim António , Maria Vasco
Published: October 2021

Background

Chronic benzodiazepine use is a challenge in primary care practice. Protocols to support safe discontinuation are still needed, especially in countries with high utilization rates.

Objectives

To evaluate the feasibility, effectiveness, and safety of a benzodiazepine discontinuation protocol in primary care setting.

Methods

Nonrandomized, single-arm interventional study, at primary care units. Family physicians (FPs) recruited patients (18–85 years-old) with benzodiazepine dependence and chronic daily use ≥3 months. Patients with daily dosages ≥30 mg diazepam-equivalent, taking zolpidem, with a history of other substance abuse or major psychiatric disease were excluded. After the switch to diazepam, the dosage was gradually tapered according to a standardized protocol. Primary endpoint was the percentage of patients who stopped benzodiazepine at the intervention last visit. Dosage reduction, withdrawal symptoms, patients’ and FPs’ satisfaction with the protocol were evaluated.

Results

From 66 enrolled patients (74% female; 66.7% aged >64 years; median time of benzodiazepine use was 120 months), 2 withdrew due to medical reasons and 3 presented protocol deviations. Overall, 59.4% of participants successfully stopped benzodiazepine (60.7% when excluding protocol deviations). Men had higher probability of success (relative risk = 0.51, P = 0.001). A total of 31 patients reported at least 1 withdrawal symptom, most frequently insomnia and anxiety. Most of participating FP considered the clinical protocol useful and feasible in daily practice. Among patients completing the protocol, 77% were satisfied. For the patients who reduced dosage, 85% kept without benzodiazepines after 12 months.

Conclusion

The discontinuation protocol with standardized dosage reduction was feasible at primary care and showed long-term effectiveness.
Endoscopic management of delayed bleeding after polypectomy of small colorectal polyps: two or more clips may be safe
Authors: Guo Xue-Feng , Yu Xiang-An , Hu Jian-Cong , Lin De-Zheng , Deng Jia-Xin , Su Ming-Li , Li Juan , Liu Wei , Zhang Jia-Wei , Zhong Qing-Hua
Published: October 2021

Background

The resection of small colorectal polyps (≤10 mm) is routine for endoscopists. However, the management of one of its main complications, namely delayed (within 14 days) postpolypectomy bleeding (DPPB), has not been clearly demonstrated. We aimed to assess the role of coloscopy in the management of DPPB from small colorectal polyps and identify the associated factors for initial hemostatic success.

Methods

We conducted a retrospective study of 69 patients who developed DPPB after the removal of colorectal polyps of ≤10 mm and underwent hemostatic colonoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2013 and June 2021. Demographics, clinical variables, and colonoscopic features were collected independently. We applied univariate and multivariate analyses to assess factors associated with initial hemostatic success.

Results

General colonoscopy without oral bowel preparation was successfully performed in all the patients, with a median duration of 23.9 (12.5–37.9) minutes. Among 69 patients, 62 (89.9%) achieved hemostasis after initial hemostatic colonoscopy and 7 (10.1%) rebled 2.7 ± 1.1 days after initial colonoscopic hemostasis and had rebleeding successfully controlled by one additional colonoscopy. No colonoscopy-related adverse events occurred. Multivariate analysis showed that management with at least two clips was the only independent prognostic factor for initial hemostatic success (odds ratio, 0.17; 95% confidence interval, 0.03–0.91; P = 0.04). All the patients who had at least two clips placed at the initial hemostatic colonoscopy required no further hemostatic intervention.

Conclusions

Colonoscopy is a safe, effective, and not too time-consuming approach for the management of patients with DPPB of small colorectal polyps and management with the placement of at least two hemoclips may be beneficial.
5. Passing Off
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter discusses the protection which the law affords to unregistered trade marks through the tort of passing off. It covers the definition of passing off; the relationship between passing off and unfair competition; the elements of both the classic and the extended form of passing off; the role of customer confusion in passing off and types of confusion, including initial interest confusion as well as reverse passing off; the types of damage resulting for an actionable misrepresentation; and defences to passing off (delay or acquiescence, bona fide use of the defendant’s own name, and concurrent use)
13. Patents III: Infringement, Exceptions, and Entitlement
Authors: Aplin Tanya , Davis Jennifer
Published: October 2021

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter discusses patent infringement, exceptions to infringement, and entitlement. Assessment of whether a patent has been infringed involves a three-stage process. First, the patent claims must be construed to see whether the defendant’s activities fall within the scope of the monopoly. Second, the infringing acts that the defendant is alleged to have carried out must be identified. Third, the applicability of exceptions to infringement must be considered. The chapter then focuses on three key exceptions to infringement within the Patents Act 1977: acts done for experimental purposes (‘experimental use’); acts done for private and non-commercial purposes (‘private use’); and the right to continue use begun before the priority date (‘prior use’). Finally, it considers persons entitled to the grant of a patent, including the role of artificial intelligence in inventorship.
2. The Legislative Sovereignty of Parliament
Authors: Thompson Brian , Gordon Michael , Tucker Adam
Published: October 2021

This chapter deals with the doctrine of the legislative sovereignty of Parliament. First, the nature of parliamentary sovereignty is considered. Next, the question of whether Parliament can limit the powers of its successors is explored, addressing possible substantive and procedural limits on legislative sovereignty. The chapter then assesses a range of modern challenges to parliamentary sovereignty: those posed by membership of and exit from the EU (including the process and impact of Brexit), human rights, the decision of the House of Lords in Jackson, common law rights and principles, and referendums.
7. Law-making
Authors: Thompson Brian , Gordon Michael , Tucker Adam
Published: October 2021

This chapter discusses law-making. First, it considers the different types of legislative measures, including the special arrangements introduced for law-making in preparation for Brexit. It then examines the methods of control and influence used before and during the consideration of legislation by Parliament, including analysis of the recently abandoned experiment with ‘English Votes for English Laws’. It concludes by analysing the process of judicial review of delegated legislation.
Cooperative planning in childcare centers to improve physical activity: a qualitative investigation of directors’ perspectives
Authors: Müller Christina , Hassel Holger
Published: October 2021

Interventions to promote physical activity (PA) in childcare centers have been shown to increase children’s PA levels; moreover, a growing number of evidence-based best practice guidelines exist for this setting. However, there is a lack of knowledge on the facilitators of and barriers to the successful implementation of PA guidelines and interventions. We used Cooperative Planning to improve capabilities for PA in childcare centers. This qualitative study aimed to explore childcare center directors’ views on the Cooperative Planning process and identify the facilitators of and barriers to its implementation. We conducted guided semi-structured interviews with the directors of nine childcare centers after completion of the 12-month Cooperative Planning process. The interviews were recorded, transcribed and analyzed using qualitative content analysis with inductive category development. Facilitators and barriers were systematized according to the Consolidated Framework for Implementation Research (CFIR). Cooperative Planning was regarded as being helpful for structuring the process and involving all team members. Several facilitators within the CFIR domains inner setting (structural characteristics, networks and communications, implementation climate), outer setting (support from parents and provider), characteristics of individuals (intrinsic motivation of the staff) and process (individual drivers) were identified. The reported barriers included structural characteristics (e.g. lack of time), networks and communications (e.g. team conflicts) and characteristics of individuals (e.g. lack of willingness to accept change). Several contextual and interpersonal factors seem to influence the extent to which a Cooperative Planning process can be implemented by a childcare center’s team. Future research is needed to evaluate the strategies needed to overcome the identified barriers.
Swedish schoolchildren’s voices of health-promoting factors: a focus group study
Authors: Einberg Eva-Lena , Golsäter Marie , Clausson Eva K
Published: October 2021

Children have the right to express their views on all issues related to their health and development. The aim was to explore health-promoting factors voiced by 8- to 12-year-old children, to determine how the children prioritize those factors and inform school personnel how to develop health-promoting approach based on those findings. Focus groups, with the use of photographs, were conducted with 15 children. A deductive content analysis was used, with overall results showing that health-promoting factors are meaningful relationships and recreational activities. The results add new perspectives to the earlier model of health-promoting factors. By highlighting children’s experience of what promotes health, measures at the individual, group and community level can be adapted to children’s priorities, based on their own needs.
A pathogenic DYT-THAP1 dystonia mutation causes hypomyelination and loss of YY1 binding
Authors: Yellajoshyula Dhananjay , Rogers Abigail E , Kim Audrey J , Kim Sumin , Pappas Samuel S , Dauer William T
Published: October 2021

Dystonia is a disabling disease that manifests as prolonged involuntary twisting movements. DYT-THAP1 is an inherited form of isolated dystonia caused by mutations in THAP1 encoding the transcription factor THAP1. The phe81leu (F81L) missense mutation is representative of a category of poorly understood mutations that do not occur on residues critical for DNA binding. Here, we demonstrate that the F81L mutation (THAP1F81L) impairs THAP1 transcriptional activity and disrupts CNS myelination. Strikingly, THAP1F81L exhibits normal DNA binding but causes a significantly reduced DNA binding of YY1, its transcriptional partner that also has an established role in oligodendrocyte lineage progression. Our results suggest a model of molecular pathogenesis whereby THAP1F81L normally binds DNA but is unable to efficiently organize an active transcription complex.
The uncertain future of the Norway lobster fisheries in the North Sea calls for new management strategies
Authors: Letschert Jonas , Stollberg Nicole , Rambo Henrike , Kempf Alexander , Berkenhagen Jörg , Stelzenmüller Vanessa
Published: October 2021

Nephrops (Nephrops norvegicus) is an economically valuable target species in the North Sea. Although individual Nephrops populations are scattered, the crustacean is managed regionally by the European Union (EU). The spatial competition for fisheries in the North Sea is growing especially due to expanding offshore wind farms (OWF) and newly implemented marine protected areas (MPA). Moreover, the Brexit affects the availability of EU fishing quotas and adds to the overall uncertainty EU fishers face. We compare landings and catches to scientifically advised quantities and perform an overlap analysis of fishing grounds with current and future OWFs and MPAs. Furthermore, we explore the German Nephrops fleet using high-resolution spatial fishing effort and catch data. Our results confirm earlier studies showing that Nephrops stocks have been fished above scientific advice. Present OWFs and MPAs marginally overlap with Nephrops fishing grounds, whereas German fishing grounds are covered up to 45% in future scenarios. Co-use strategies with OWFs could mitigate the loss of fishing opportunities. Decreased cod quotas due to Brexit and worse stock conditions, lowers Germany's capability to swap Nephrops quotas with the UK. We support the call for a new management strategy of individual Nephrops populations and the promotion of selective fishing gears.
Effects of a marine heatwave on adult body length of three numerically dominant krill species in the California Current Ecosystem
Authors: Killeen Helen , Dorman Jeffrey , Sydeman William , Dibble Connor , Morgan Steven
Published: October 2021

Krill are an abundant and globally distributed forage taxon in marine ecosystems, including the California Current Ecosystem (CCE). The role of krill in trophodynamics depends on both abundance and size (biomass), but the impact of extreme climate events on krill body size is poorly understood. Using samples collected from 2011 to 2018, we tested the hypotheses that adult body length of three krill species (Euphausia pacifica, Thysanoessa spinifera, and Nematoscelis difficilis) declined during the 2014–2016 Northeast Pacific marine heatwave/El Niño event due to elevated seawater temperatures, reduced upwelling, and low primary productivity. Hierarchical mixed-effects modelling showed that mean length of adult E. pacifica and T. spinifera declined and N. difficilis length increased during 2015. These trends differed by sex and reverted to a pre-heatwave state in 2016. Temperature, upwelling, and food availability (chlorophyll-a content) did not explain decreased length in 2015, but environmental drivers of length varied regionally and by sex across all years. This study documents the impact of a major marine heatwave (MHW) on adult krill length in one of the world's major upwelling systems and indicates how pelagic ecosystems may respond to increasingly frequent MHWs.
Proposed business rules to incorporate climate-induced changes in fisheries management
Authors: Link J S , Karp M A , Lynch P , Morrison W E , Peterson J
Published: October 2021

Changing oceanic conditions are having impacts on living marine resources (LMRs) and their management, often in ways beyond what we have ever seen before. This is largely manifested as changes in production or location of these LMRs. The challenge has been not only to disentangle the possible causes of these changes to LMR stocks, but then even if clear changes are detected, it has been unclear what we can actually do about them. Here, we propose a set of recommended actions or “business rules” to better address climate-induced changes to LMR production and location. These emphasize a series of diagnostics which can be used to demarcate significance of whether action is necessary, and then if action is deemed necessary, we propose a set of insertion points or “on-ramps” to address the nuances of locational or production changes at every step in the science to management process. These proposed “business rules” for dealing with climate-induced changes to fisheries can always be debated, can always be updated with new information, and can always be adjusted under a given set of circumstances. But, we also assert that it would be wise to start acting on them, as a proposed set of options, given the urgency and exigency of the situation.
Retos de la jurisprudencia de la Corte Interamericana de Derechos Humanos en la categorización de conductas como crímenes internacionalesChallenges of the Inter-American Court of Human Rights’ jurisprudence in the categorization of conducts as international crimes
Authors: Acosta-López Juana , Idárraga Ana
Published: October 2021

The Inter-American Court of Human Rights has been carrying out a harmonious application of various regimes of International Law, in particular International Human Rights Law and International Criminal Law. One of the results of this harmonious application is the use of the figure of international crimes in its jurisprudence. This text explores the requirements of provenance that have been developed by the jurisprudence of the Inter-American Court for the application of the figure of international crimes in the contentious cases of the Court, as well as the challenges that derive from this application. Some of these challenges are: (i) different legal qualifications of the same facts due to the differences between the evidentiary standards of human rights and international criminal law; (ii) possible effects on the judicial independence of national judges; and (iii) possible effects on the criminal guarantees of those allegedly responsible for the crimes.
DA-Raf and the MEK inhibitor trametinib reverse skeletal myocyte differentiation inhibition or muscle atrophy caused by myostatin and GDF11 through the non-Smad Ras–ERK pathway
Authors: Masuzawa Ryuichi , Takahashi Kazuya , Takano Kazunori , Nishino Ichizo , Sakai Toshiyuki , Endo Takeshi
Published: October 2021

Myostatin (Mstn) and GDF11 are critical factors that are involved in muscle atrophy in the young and sarcopenia in the elderly, respectively. These TGF-β superfamily proteins activate not only Smad signalling but also non-Smad signalling including the Ras-mediated ERK pathway (Raf–MEK–ERK phosphorylation cascade). Although Mstn and GDF11 have been shown to induce muscle atrophy or sarcopenia by Smad2/3-mediated Akt inhibition, participation of the non-Smad Ras–ERK pathway in atrophy and sarcopenia has not been well determined. We show here that both Mstn and GDF11 prevented skeletal myocyte differentiation but that the MEK inhibitor U0126 or trametinib restored differentiation in Mstn- or GDF11-treated myocytes. These MEK inhibitors induced the expression of DA-Raf1 (DA-Raf), which is a dominant-negative antagonist of the Ras–ERK pathway. Exogenous expression of DA-Raf in Mstn- or GDF11-treated myocytes restored differentiation. Furthermore, administration of trametinib to aged mice resulted in an increase in myofiber size or recovery from muscle atrophy. The trametinib administration downregulated ERK activity in these muscles. These results imply that the Mstn/GDF11-induced Ras–ERK pathway plays critical roles in the inhibition of myocyte differentiation and muscle regeneration, which leads to muscle atrophy. Trametinib and similar approved drugs might be applicable to the treatment of muscle atrophy in sarcopenia or cachexia.
US Supreme Court upholds assignor estoppel while narrowing the doctrine
Authors: Macedo Charles R , Goldberg David P , Sturm Chandler , Garrity Devin , Hart Thomas
Published: October 2021

Minerva Surgical, Inc. v Hologic, Inc., No. 20–440, 594 US ___, United States Supreme Court, 29 June 2021 (Minerva)

Hologic, Inc. v Minerva Surgical, Inc., 957 F3d 1256 (Federal Circuit 2020) (‘Hologic’), rehearing and rehearing en banc denied, petition for certiorari filed

On 29 June 2021, the US Supreme Court issued a decision in Minerva Surgical, Inc. v Hologic, Inc. upholding the doctrine of assignor estoppel, which prevents inventors from challenging the validity of patents they have assigned to third parties. The court limited the scope of assignor estoppel to cases where the inventor made ‘explicit or implicit representations’ regarding the patentability of the claimed invention.
Are cyclic plant and animal behaviours driven by gravimetric mechanical forces?
Authors: de Mello Gallep Cristiano , Robert Daniel
Published: October 2021

The celestial mechanics of the Sun, Moon, and Earth dominate the variations in gravitational force that all matter, live or inert, experiences on Earth. Expressed as gravimetric tides, these variations are pervasive and have forever been part of the physical ecology with which organisms evolved. Here, we first offer a brief review of previously proposed explanations that gravimetric tides constitute a tangible and potent force shaping the rhythmic activities of organisms. Through meta-analysis, we then interrogate data from three study cases and show the close association between the omnipresent gravimetric tides and cyclic activity. As exemplified by free-running cyclic locomotor activity in isopods, reproductive effort in coral, and modulation of growth in seedlings, biological rhythms coincide with temporal patterns of the local gravimetric tide. These data reveal that, in the presumed absence of rhythmic cues such as light and temperature, local gravimetric tide is sufficient to entrain cyclic behaviour. The present evidence thus questions the phenomenological significance of so-called free-run experiments.
Large optical modulations during 2018 outburst of MAXI J1820 + 070 reveal evolution of warped accretion disc through X-ray state change
Authors: Thomas Jessymol K , Charles Philip A , Buckley David A H , Kotze Marissa M , Lasota Jean-Pierre , Potter Stephen B , Steiner James F , Paice John A
Published: October 2021

The black hole X-ray transient MAXI J1820 + 070  (= ASSASN-18ey) discovered in 2018 March was one of the optically brightest ever seen, which has resulted in very detailed optical outburst light curves being obtained. We combine them here with X-ray and radio light curves to show the major geometric changes the source undergoes. We present a detailed temporal analysis that reveals the presence of remarkably high amplitude (>0.5 mag) modulations, which evolve from the superhump (16.87 h) period towards the presumed orbital (16.45 h) period. These modulations appear ∼87 d after the outburst began, and follow the Swift/BAT hard X-ray light curve, which peaks 4 d before the radio flare and jet ejection, when the source undergoes a rapid hard to soft state transition. The optical modulation then moves closer to the orbital period, with a light-curve peak that drifts slowly in orbital phase from ∼0.8 to ∼0.3 during the soft state. We propose that the unprecedentedly large amplitude modulation requires a warp in the disc in order to provide a large enough radiating area, and for the warp to be irradiation driven. Its sudden turn-on implies a change in the inner disc geometry that raises the hard X-ray-emitting component to a height where it can illuminate the warped outer disc regions.
Differences in patients’ population and efficacy/effectiveness of biologic disease–modifying antirheumatic drugs between randomized controlled trials and real-world settings in patients with rheumatoid arthritis – using the IORRA cohort
Authors: Sugano Eri , Tanaka Eiichi , Inoue Eisuke , Sakai Ryoko , Abe Mai , Saka Kumiko , Sugitani Naohiro , Ochiai Moeko , Yamaguchi Rei , Higuchi Yoko , Sugimoto Naoki , Ikari Katsunori , Nakajima Ayako , Yamanaka Hisashi , Harigai Masayoshi
Published: October 2021

Objectives

To evaluate the differences in patients’ population and efficacy/effectiveness of biological disease–modifying antirheumatic drugs (bDMARDs) between randomized controlled trials (RCTs) and clinical practice in patients with rheumatoid arthritis.

Methods

We reviewed inclusion criteria in Phase II or III RCTs of bDMARDs conducted in Japan. The Institute of Rheumatology, Rheumatoid Arthritis study participants during the period when each RCT was conducted (Cohort A) and new bDMARD users at our institute in 2016 (Cohort B) were assessed for the fulfilment of the inclusion criteria. The effectiveness of bDMARDs in our cohort and their efficacy in RCTs were compared using the inverse-variance method.

Results

Nineteen RCTs were selected. The mean proportions of patients fulfilling all inclusion criteria of each RCT in Cohorts A and B were 2.3% and 7.6%, respectively. The pooled proportion ratios (95% confidence interval) for achieving the American College of Rheumatology 20 (ACR20), ACR50, ACR70, and disease activity score 28 remission in non-eligible cases for eight RCTs versus all corresponding RCTs were 0.38 (0.30–0.51), 0.41 (0.30–0.57), 0.54 (0.35–0.82), and 1.28 (1.10–1.56), respectively.

Conclusions

Few rheumatoid arthritis patients fulfilled the inclusion criteria of the RCTs in clinical settings. There was a difference in the efficacy/effectiveness of bDMARDs between RCTs and clinical practice.
Decrease of infectious complications in outpatients with autoimmune diseases from 2019 to 2020 under the COVID-19 pandemic: A single-centre, retrospective cohort study in Japan
Authors: Oka Yumiko , Kodera Takao , Takeshita Miki , Shirota Yuko , Takeda Tomoki , Tsutsumi Tomomi , Kameoka Junichi
Published: October 2021

Objectives

To examine how the novel coronavirus disease (COVID-19) has changed infectious complications in outpatients with autoimmune diseases.

Methods

We performed a retrospective, record-linked cohort study and questionnaire about lifestyle changes in patients who visited our department in 2019 and 2020.

Results

We surveyed 1316 outpatients in 2019 and 1284 in 2020. The most common underlying diseases were rheumatoid arthritis (842 vs. 814) and systemic lupus erythematosus (SLE) (126 vs. 127). No significant difference in median age (66 vs. 67 years), respiratory comorbidities (30.4% vs. 32.0%), or corticosteroid use (42.2% vs. 44.3%) was found between the years. Immunomodulating agents were used more in 2020 (33.1% vs. 39.7%, p < .001). Total number of infections (28.0/100 vs. 19.4/100 person-years), pneumonia (3.6 vs. 1.6), influenza (2.1 vs. 0.1), and nonviral dermatological infections (3.8 vs. 2.1) were significantly lower in 2020. No significant difference was found for herpes zoster (2.2 vs. 1.8), urinary tract infections (3.3 vs. 3.8), or gastrointestinal infections (2.9 vs. 3.0). According to the questionnaire, 75% of the respondents became more conscious about wearing masks and 81% began to use hand sanitizer during the pandemic.

Conclusion

Under the COVID-19 pandemic, some infectious complications have decreased in outpatients with autoimmune diseases.
Foot and ankle functions and deformities focus on posterior tibial tendon dysfunction using magnetic resonance imaging in patients with rheumatoid arthritis
Authors: Mochizuki Takeshi , Nasu Yuki , Yano Koichiro , Ikari Katsunori , Hiroshima Ryo , Okazaki Ken
Published: October 2021

Objectives

Posterior tibial tendon dysfunction (PTTD) affects the support of the medial longitudinal arch and stability of the hindfoot. The purpose of this study was to assess the relationships of PTTD with foot and ankle functions and foot deformities in patients with rheumatoid arthritis (RA).

Methods

A total of 129 patients (258 feet) who underwent magnetic plain and contrast-enhanced magnetic resonance imaging were enrolled in this study. Positive magnetic resonance imaging findings were defined as tenosynovitis and incomplete and complete rupture of the posterior tibial tendon. Foot and ankle functions were assessed using the Japanese Society for Surgery of the Foot standard rating system for the RA foot and ankle scale (JSSF-RA) and self-administered foot evaluation questionnaire. Plain radiographs were examined for the hallux valgus angle, first metatarsal and second metatarsal angle, lateral talo-first metatarsal angle, and calcaneal pitch angle.

Results

PTTD was associated with motion in the JSSF-RA (p = .024), activities of daily living in JSSF-RA (p = .017), and pain and pain-related factors in the self-administered foot evaluation questionnaire (p = .001). The calcaneal pitch angle was significantly lower in the feet with PTTD than in those without PTTD (median: 16.2° vs. 18.0°; p = .007).

Conclusions

The present study shows that PTTD was associated with foot and ankle functions and flatfoot deformity. Thus, a better understanding of PTTD in patients with RA is important for the management of foot and ankle disorders in clinical practice.
Effect of a multitarget therapy with prednisolone, mycophenolate mofetil, and tacrolimus in a patient with type B insulin resistance syndrome complicated by lupus nephritis
Authors: Temmoku Jumpei , Asano Tomoyuki , Saito Kenji , Matsumoto Haruki , Fujita Yuya , Furuya-Yashiro Makiko , Matsuoka Naoki , Oda Akira , Tanabe Hayato , Sato Shuzo , Shio-Yano Kiori , Sasajima Tomomi , Kiko Yuichiro , Kobayashi Hiroko , Watanabe Hiroshi , Shimabukuro Michio , Migita Kiyoshi
Published: October 2021

Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease characterised by autoantibodies targeting insulin receptors. TBIR is often complicated by systemic lupus erythematosus (SLE). We describe the case of a 59-year-old Japanese man with TBIR complicated with lupus nephritis (LN), who presented with nephrotic syndrome and severe hypoglycaemia. Treatment with prednisolone (PSL), mycophenolate mofetil (MMF), and tacrolimus (TAC) resulted in improved SLE activity and glucose intolerance with the reduction of anti-insulin receptor autoantibodies. To the best of our knowledge, this is the first reported case of TBIR complicated with LN that was successfully treated using multitarget therapy with PSL, MMF, and TAC.
Readmission and reoperation rates after resection of malignant primary brain tumours in England 2013-2017
Authors: Wahba Adam , Phillips Nick , Hutchinson Peter , Cromwell David , Mathew Ryan
Published: October 2021

Aims

Morbidity and mortality following resection of malignant primary brain tumours is high. The benefits of reoperation for recurrent tumours are uncertain and it is not known how frequently patients in England undergo further tumour resections. The aim of this study was to describe 30-day and one-year readmission rates, the clinical reasons for readmission and the rate of resections for recurrent tumours.

Method

Patient data was extracted from Hospital Episode Statistics (the hospital administrative data for NHS hospitals in England) for all supratentorial, malignant, primary brain tumour resections performed from April 2013 to March 2017. All subsequent non-elective readmissions to any NHS hospital and all readmissions for further tumour resection within 30 days and one year were analysed for the primary clinical diagnosis and primary procedure performed.

Results

A total of 6,982 patients were identified and the 30-day and one-year readmission rates were 18.6% (n=1,298) and 57.4% (n=4,007), respectively. The rates of reoperation for tumour resection were 0.5% (n=33) and 6.2% (n=432), respectively. The commonest reasons for 30-day readmission were post-operative complications (17.9% of admissions), general medical complications (17.3%) and surgical site infection (9.6%). The most frequently performed neurosurgical procedures were for treatment of surgical site infection (37.6% of procedures). The commonest reasons for readmission within one year were general medical complications (17.4%), seizures (14%), systemic infections (11.4%) and post-operative complications (11%). Almost half of all neurosurgical procedures performed within one year were reoperation for tumour resection (45.6%), while treatment of surgical site infection (17.9%) and CSF shunt insertions and revisions (9.1%) were also common.

Conclusion

This study provides a descriptive analysis of the rates of readmission, diagnosis on readmission, and the need for further neurosurgical procedures. The rate of non-elective readmissions within one year is high and these data may be useful for service planning and for counselling patients about their treatment. Additionally, these data contribute to the development of quality indicators, for benchmarking and comparing quality of care provision between neurosurgical units. Further research, with linkage to histology data and performance status, would support an analysis of the role of resection of recurrent, malignant, primary brain tumours.
Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation
Authors: Poologaindran Anujan , Hart Mike , Santarius Tom , Price Stephen , Sinha Rohit , Sughrue Mike , Erez Yaara , Romero-Garcia Rafael , Suckling John
Published: October 2021

Aims

Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the “mesoscale” architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following aims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (>1 year).

Method

With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, & 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories.

Results

Controlling for age and sex, the MD system’s multi-scale architecture in health was positively associated with higher-order cognition (Catell’s fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity.

Conclusion

This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.
The use of cannabinoid and non-cannabinoid supplementary therapies in patients undergoing treatment for Glioblastoma reveals an urgent need for guidance
Authors: Vaqas Babar , Dulley Louise , Maniar Ruchi
Published: October 2021

Aims

Glioblastoma (GBM) is currently an incurable malignancy with a very poor prognosis for the majority of patients. Many patients undergo debulking surgery, radiotherapy and chemotherapy however therapeutic options are limited, and this can lead to patients sourcing their own treatments. There is some evidence that cannabinoids have the effect of inhibiting GBM tumour growth through a variety of pathways, some of which include CB2 cannabinoid receptor pathway activation. We undertook a patient questionnaire to understand what alternative therapies patients are accessing and why, with a focus on cannabinoid use.

Method

We undertook a prospective observational questionnaire based qualitative study of 50 … consecutive patients undergoing treatment for glioblastoma at our centre.

Results

43 patients responded to our questionnaire. 33% of patients were taking some kind of supplementary therapy with 25% taking cannabis derivatives, mainly CBD oil. There were no clear discriminators amongst our cohort including age or sex when considering the likelihood of taking cannabis derivatives. 6 out of 11 (55%) patients taking cannabis derivatives reported some positive effects with improved sleep and general wellbeing being most commonly reported. Patients reported spending between £10-£300 per month with an average of £42 per month. Cannabis products were obtained via the internet or from friends.

Conclusion

This small cohort of patients indicates that a significant proportion of glioblastoma patients investigate and use alternative therapies, in particular cannabis oil. NICE guidance for clinicians simply notes there is insufficient evidence to support the use of cannabis oil in the treatment of this disease. Given the publicity and interest in the utility of cannabis oil to treat cancers this leaves patients to research the use of these agents without access to robust clinical data to guide their use or indeed to conclude they are not beneficial. The accessing of these compounds, potentially by a sizeable number of patients, leaves them vulnerable to unregulated perhaps unscrupulous drug sources. This small study has further highlighted the unmet need for information and guidance on supplementary treatments for glioma patients and this poses a challenge to all those treating this group of patients to answer a question our patients are clearly wanting answered.
Temozolomide hypersensitivity – A story of success
Authors: Alagiyawanna Lanka , Prince Stephanie , Wright Debbie , Clarke Enrico , Ching Jeng
Published: October 2021

Aims

Background:

Temozolomide is an oral chemotherapy drug widely used in the treatment of glial tumours. This is generally well tolerated however, immediate and delayed hypersensitivity reactions have been described, necessitating treatment interruption that could significantly impact survival.

Method

Case description:

We report a case of a 39-year-old young woman with WHO grade 2 IDH1mutant diffuse astrocytoma (MGMT promoter methylated) of the left temporal lobe. She had tumour resection in 2012 followed by radical radiotherapy. Afterwards, she had close surveillance with regular brain imaging. The tumour started to progress in early 2020. We agreed to commence on temozolomide to control tumour growth.

She developed an itchy rash with easy bruising towards the end of the first cycle. It responded to a course of prednisolone. We proceeded with the second cycle and she developed a worsening rash on the third day. However she did not have signs or symptoms of anaphylaxis. This episode was again managed by a course of steroids and oral antibiotics. Since Temozolomide was the optimal treatment to control the disease progression at this stage, we agreed to persevere with temozolomide using a rapid desensitisation protocol.

Results

On the first day of third cycle, she was brought to the day chemotherapy unit and given prednisolone 30mg, fexofenadine 180mg and ondansetron 8mg, 30 minutes before the treatment. Our protocol was as follows; 5mg, 10mg, 20mg, 30mg, 50mg and 90mg of temozolomide at an interval of 30 minutes between the doses. She was advised to follow the same regime for the next four days of the third cycle. On days 6 -28, she has been advised to take fexofenadine 180mg once daily. Although there was a minor rash appeared on days 6/7, they subsided gradually. She tolerated the treatment without sinister symptoms or signs. We proceeded with the next 4 chemotherapy cycles adhering to the same protocol. The intensity of the rash gradually improved, and she became almost completely asymptomatic by the 7th cycle. It was also encouraging to see the radiological response of the tumour with the treatment.

Conclusion

Although the published literature is minimal, rapid desensitisation is shown to be a safe and effective method to counteract temozolomide hypersensitivity. In an era where there is still a paucity of systemic treatment options for primary brain tumours, adopting rapid desensitisation to induce tolerability to temozolomide, a drug which has shown to improve survival, would be a valuable addition in managing our patients. Further, our experience suggests that this protocol is safe, effective, and does not necessitate inpatient admission.
Resident physicians physical activity during on-call shifts: smartphone-based assessment
Authors: Ben-David R , Savin Z , Herzberg H , Shulman Y , Bar-Yakkov N , Haham A , Yossepowitch O , Sofer M
Published: October 2021

Background

Physical activity of resident physicians (RPs) during on-call shifts is difficult to objectively evaluate. The integration of smartphones in our daily routines may allow quantitative assessment, employing pedometric assessment.

Aims

To evaluate the number of steps that RPs walk during on-call shifts as a marker of physical activity by using smartphone-based pedometers.

Methods

Step counts were collected from 100 RPs’ smartphones who volunteered to participate in the study between January 2018 and May 2019. The conversion rate was 1400 steps = 1 km (application’s default). A shift was defined as regular morning work followed by an in-house on-call stay, totalling 26 hours. Statistical analyses included univariate and multivariate linear mixed models, and Fisher exact test. A P-value < 0.05 was considered statistically significant.

Results

The average walking distance was 12 118 steps (8.6 km/RP/shift). Paediatric intensive care unit and neurosurgery residents recorded the longest walking distances 16 347 and 15 630 steps (11.67 and 11.16 km/shift), respectively. Radiology residents walked the shortest distances 4718 steps (3.37 km/shift). Physically active RPs walked significantly longer distances during their shifts than non-physically active RPs: 12 527 steps versus 11 384 steps (8.95 versus 8.13 km/shift, P < 0.05), respectively. Distances covered during weekday shifts were longer than weekend shifts: 12 092 steps versus 11 570 steps (8.63 versus 8.26 km/shift, P < 0.05), respectively.

Conclusions

Smartphone-based pedometers can aid in analysing physical activity and workload during on-call shifts; such information can be valuable for human resource department, occupational health authorities and medical students with impaired physical mobility when choosing a speciality.
Is Judaism a Religion, and Why Should We Care?
Authors: Magid Shaul
Published: October 2021

In this chapter, Shaul Magid ask an important question: How does the study of religion, writ large, help us in the study of specific religions, in his case Judaism. In particular, he argues that, in some ways, Judaism is and is not a religion. He focuses particularly on the assessment of Jonathan Z. Smith. Nicola Denzey Lewis responds to Magid by claiming that the traditional world religions model that she was exposed to in graduate school now seems untenable in the modern world, especially given the critiques of that model and the definition of religion that it historically worked with.
The Semantic Subject: Religion and the Limits of Language
Authors: Zoloth Laurie
Published: October 2021

In this chapter Laurie Zoloth and Craig Martin debate the utility of Martin’s initial definition of religion as a “slippery” term that is difficult to define. Zoloth takes issue with Martin’s claim that many scholars of religion are “willfully ignorant” since they are unwilling (or unable) to differentiate between religion and other related categories (e.g., the social, the cultural); she instead prefers to see religion as possessing some content. She argues that the category “religion,” far from meaningless, is actually so broad that it demands we focus on it more closely than has traditionally been done and that this is important from the perspective of sociological research. Martin responds that, if our definition is left vague, we do not study anything and will not be taken seriously by our peers in other fields of study.
Is (What Gets Called) Religion an Argument, Discourse, or Ideology?
Authors: Nye Malory
Published: October 2021

In this chapter Malory Nye and Laurie L. Patton debate the idea of religion. Patton, in her initial definition, stresses the communal, belief structures, and notions of authority. Nye instead argues that religion is essentially nothing (no-thing) and is based on the social construction of reality. Nye further objects to the idea that religion has anything to do with so-called ultimate values and again points to the social construction of religion; he prefers to see religion, in good Marxist fashion, as a way for the proletariat to cope with the disadvantages of capitalism. For him, religion is an ideology, something that can appear as neutral or benevolent, but often is neither.
Arguments against the Textualization Regime
Authors: Koch Anne
Published: October 2021

In this chapter Anne Koch and Vincent L. Wimbush debate the role of scripture in the study of religion and using this term as a key phrase in attempting to define it. In his initial definition, Wimbish argues that “ ‘[s]cripturalization’ . . . best captures the larger psychosocial, political-economic, and metadiscursive regime—shaping and shaped by nation-states—by which all are scripturally managed.” Koch responds with the claim that it is too narrow a definition and that we need to go even further; she suggests the use of “[s]emiotics—including grammar, meaning generation, time constructions, the way signs relate to objects, evaluations of repetition—and narratives (including excerpts from narratives as well as entire stories)” as “highly powerful structures in societies.”
No Standard Oil
Authors: Gordon Deborah
Published: October 2021

The next decade will be decisive in the fight against climate change. It will be impossible to hold the planet to a 1.5 degrees Celsius temperature rise without controlling methane and carbon dioxide emissions from the oil and gas sector. Contrary to popular belief, the world will not run out of these resources anytime soon. Instead, oil and gas are becoming more climate-intensive to supply using technologies like fracking oil and liquefying gas—even as these abundant resources continue to be used to fuel cars, heat homes, and produce consumer goods like shampoo, pajamas, and paint. Policymakers, financial investors, environmental advocates, and citizens need to understand what oils and fossil fuels are doing to our climate to inform decision-making. In No Standard Oil, Deborah Gordon shows that no two oils or gases are environmentally alike. Each has a distinct, quantifiable climate impact. While all oils and gases pollute, some are much worse for the climate than others. In clear, accessible language, Gordon explains the results of the Oil Climate Index Plus Gas (OCI+), an innovative, open-source model that estimates global oil and gas greenhouse gas emissions. Gordon identifies the oils and gases from every region of the globe—along with the specific production, processing, and refining activities—that are the most damaging to the planet and proposes innovative solutions to reduce their climate footprints. Global climate stabilization cannot afford to wait for oil and gas to run out. No Standard Oil shows how people can take immediate, practical steps to cut greenhouse gas emissions in the crucial oil and gas sector while making sustainable progress in transitioning to a carbon-free energy future.