bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ought the level of sedation to be reduced during deep palliative sedation? A clinical and ethical analysis
Authors: Fredheim Olav Magnus , Materstvedt Lars Johan , Skulberg Ingeborg , Magelssen Morten 
Published: October 2021

BackgroundDeep palliative sedation (DPS) is applied as a response to refractory suffering at the end of life when symptoms cannot be relieved in an awake state. DPS entails a dilemma of whether to provide uninterrupted sedation—in which case DPS would turn into deep and continuous palliative sedation (DCPS) —to minimise the risk that any further intolerable suffering will occur or whether to pause sedation to avoid unnecessary sedation. DPS is problematic in that it leaves the patient ‘socially dead’ by eradicating their autonomy and conscious experiences.AimTo perform a normative ethical analysis of whether guidelines should recommend attempting to elevate consciousness during DPS.DesignA structured analysis based on the four principles of healthcare ethics and consideration of stakeholders’ interests.ResultsWhen DPS is initiated it reflects that symptom relief is valued above the patient’s ability to exercise autonomy and experience social interaction. However, if a decrease in symptom burden occurs, waking could be performed without patients experiencing suffering. Such pausing of deep sedation would satisfy the principles of autonomy and beneficence. Certain patients require substantial dose increases to maintain sedation. Waking such patients risks causing distressing symptoms. This does not happen if deep sedation is kept uninterrupted. Thus, the principle of non-maleficence points towards not pausing sedation. The authors’ clinical ethics analysis demonstrates why other stakeholders’ interests do not appear to override arguments in favour of providing uninterrupted sedation.ConclusionStopping or pausing DPS should always be considered, but should not be routinely attempted.
Medical Experience in Nuclear Submarines
Authors: Davies D. M. 
Published: October 2021

AbstractA summary of medical experience gained on long detached patrols by British nuclear submarine medical officers is presented. Comparisons with American experience are made and indications of what the new submarine medical officer may expect to meet in his practice at sea on patrol are given. The picture reflects the good standard of health of the British submariner and the success of the preventive medicine programme.
A Case of Familial Hypercholesterolaemia Associated with Xanthoma Tuberosum Multiplex
Authors: Chakraverty A. C. 
Published: October 2021

AbstractA case of familial hvpercholesterolaemia (Frederickson Type II–hyperlipoproteinaemia) associated with xanthoma tuberosum multiplex is described. This condition is very unusual even in its typical form. The clinical presentation and diagnosis are discussed. Confusion with benign synovioma must be avoided.
The Significance of Fungal Growth in Nuclear Submarines
Authors: Doris I. , Harper M. G. , Morris J. E. W. 
Published: October 2021

AbstractThe visible presence of fungal growth in certain areas of nuclear submarines has given rise to concern amongst the crews. The airborne spore population was investigated to determine the medical significance of such growths and the methods used are described. It is concluded that no medical hazards are associated with the presence of fungal growths, but that action is necessary to deal with the material deterioration caused by the growths. The overall investigation is a good example of how medical, scientific and engineering staff within the Ministry of Defence (Naval) can work closely together to resolve such problems to mutual benefit.
The Waterhouse-Friderichsen Syndrome and its Orthopaedic Consequences
Authors: Hampton Trevor R. W. , Gordon Pugh P. D. 
Published: October 2021

AbstractTwo cases of fulminating meningococcal septicaemia with Waterhouse-Friderichsen syndrome are reported in young servicemen. Both were complicated by peripheral gangrene of unusual severity, which required the modification of standard surgical procedures to meet their individual requirements. The rationale of management is discussed in the light of the pathological processes involved, and views are advanced on the place of steroids and heparin in the acute stage.
Influenza Vaccination in a Training Establishment
Authors: Gill J. B. , Fraser P. K. , Smith J. W. G. 
Published: October 2021

AbstractOf 1,586 boys in a Naval Junior Training Establishment, 61% were inoculated in December 1971 with a bivalent vaccine containing 400 CCA units of the Hong Kong strain of influenza A virus. Approximately 4 weeks later an outbreak of influenza developed, caused by the Hong Kong virus. The overall attack rate was 9.5%. Of the unvaccinated boys 16.7% became ill, and of the vaccinated boys 4.9%. Serological evidence of infection was detected in 19% of the vaccinated boys and 59% of unvaccinated boys who became ill. It is suggested that the vaccination programme prevented at least 114 cases of influenza in the establishment.
Assay of Strontium-90 in Human Permanent Teeth in the United Kingdom 1966-1971
Authors: Starkey W. E. , Brooks W. L. 
Published: October 2021

AbstractA survey of the accumulation of 90Sr in human teeth has been carried out by the Royal Navy. It covers the 13 years 1959-71 in which fallout levels rose to a peak and declined again. Correlations have been established between the uptake of 90Sr in developing tooth and bone, related to fluctuating ratios of 90Sr/Ca in the diet. Since mineral ratios are permanently fixed in teeth by irreversible deposition they constitute an indelible record of the levels of bone-seeking elements (including contaminants) that existed when the teeth were being laid down. Thus it becomes possible to estimate former bone ratios persisting in the teeth, no matter how much prevailing levels of contamination may have altered in the meantime. The present study provides general parameters whereby this may be done.
A Preliminary Study into Factors Predisposing Mountaineers to High Altitude Pulmonary Oedema
Authors: Bulstrode C. J. K. 
Published: October 2021

AbstractHigh Altitude Pulmonary Oedema (HAPO), is an acute rapidly progressive and sometimes fatal respiratory disorder developing in healthy mountaineers climbing to high altitudes.A short preliminary study was carried out on Mt Kenya to investigate the changes in electrolyte and water distribution occurring in people who climb rapidly to altitude, and to discover to what extent these might be responsible for the development of HAPO.
Human and Experimental Factors in Protracted Isolation Studies
Authors: Davies D. M. 
Published: October 2021

AbstractDuring the past two years, in a series of studies into the effects of abnormal atmospheres on man, volunteer Naval subjects have been physically isolated from the outside world, in a large exposure chamber, continuously for periods of up to 81 days. The planning and execution of these studies revealed questions, the answers to which could neither he deduced from available experience nor logically forecast. Some of I he human and experimental problems involved are examined, and the ways in which they were tackled are discussed together with an asessment of the main lessons learnt during these relatively unique studies.
Fluoride Concentrations of Surface Enamel before and after Topical Application of Stannous Fluoride in Naval Recruits
Authors: Coppock D. A. 
Published: October 2021

AbstractThe inhibitory effect of fluoride on dental caries is well established, but the exact mechanism of caries prevention is unknown. It has been hypothesised that the effectiveness of topically applied fluoride depends upon its ability to incorporate fluoride into tooth enamel. The purpose of this study was to determine the extent of fluoride uptake in enamel achieved by the topical application of stannous fluoride on Naval Recruits.The 112 Naval Recruits were randomly divided into two equal groups for the study. The experimental group underwent supervised toothbrushing with an 8.9 per cent stannous fluoride prophylaxis paste followed by a 15 second application of a 10 per cent stannous fluoride solution. The control group received no fluoride. Enamel samples were taken from one maxillary central inc;sor of each group initially and again 18 hours after fluoride treatment from the opposite central incisor.The in vivo enamel biopsy technique devised by Brudevold and modified by IVIellberg for measuring fluoride concentrations in enamel was used. The samples were obtained by abrading a limited area of enamel, on the labial surface of the maxillary central incisor teeth, with a rotary felt cone and silicone carbide. The slurry was then collected and analysed for calcium and fluoride content, using an atomic absorption spectrophotometer and a fluoride specific electrode, respectively.An increase in fluoride content of 5 per cent for the group with fluoride witheld, and 13 per cent for the group with fluoride applied were not s:gnificant.The average mean depth for enamel samples was 4.7µm ± 0.7. The differences between depths of the various groups was not significant.Although no significant fluoride uptake was found, it was concluded, because of consistent results obtained with the biopsy technique, that it is a useful tool for further studies of his nature.
The Determination of Antithrombin III and its Clinical Application
Authors: Gray S. P. , Billings J. A. 
Published: October 2021

AbstractA preliminary study of antithrombin III levels in the blood of three groups of patients, women taking the contraceptive pill, patients on warfarin therapy and a group with a variety of non-vascular complaints, has been carried out using a newly developed automated method. No age or sex difference was found, but women on the contraceptive pill have a significantly lowered antithrombin III activity in the blood, and warfarin-treated patients have a significantly increased activity. It is suggested that, as antithrombin III acts as an inhibitor in the complement, coagulation, fibrinolytic and kallikrein-kinin systems and lowered activity predisposes to venous thrombosis, its measurement should be carried out in all those patients at risk in the post-operative phase.
Neoadjuvant STING Activation, Extended Half-life IL2, and Checkpoint Blockade Promote Metastasis Clearance via Sustained NK-cell Activation
Authors: Milling Lauren E. , Garafola Daniel , Agarwal Yash , Wu Shengwei , Thomas Ayush , Donahue Nathan , Adams Josetta , Thai Nikki , Suh Heikyung , Irvine Darrell J. 
Published: October 2021

Abstract

Combination immunotherapy treatments that recruit both innate and adaptive immunity have the potential to increase cancer response rates by engaging a more complete repertoire of effector mechanisms. Here, we combined intratumoral STimulator of INterferon Genes (STING) agonist therapy with systemically injected extended half-life IL2 and anti–PD-1 checkpoint blockade (hereafter CIP therapy) to drive innate and adaptive antitumor immunity in models of triple-negative breast cancer. Unlike treatment with the individual components, this trivalent immunotherapy halted primary tumor progression and led to long-term remission for a majority of animals in two spontaneously metastasizing orthotopic breast tumor models, though only as a neoadjuvant therapy but not adjuvant therapy. CIP therapy induced antitumor T-cell responses, but protection from metastatic relapse depended on natural killer (NK) cells. The combination of STING agonists with IL2/anti–PD-1 synergized to stimulate sustained granzyme and cytokine expression by lung-infiltrating NK cells. Type I IFNs generated as a result of STING agonism, combined with IL2, acted in a positive-feedback loop by enhancing the expression of IFNAR-1 and CD25 on lung NK cells. These results suggest that NK cells can be therapeutically targeted to effectively eliminate tumor metastases.
See related Spotlight by Demaria, p. 3 .
Impact of Periprocedural Myocardial Injury and Infarction Definitions on Long-Term Mortality After Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Song Lei , Wang Yang , Guan Changdong , Zou Tongqiang , Sun Zhongwei , Xie Lihua , Zhang Rui , Dou Kefei , Yang Weixian , Wu Yongjian , Qiao Shubin , Xu Bo 
Published: October 2021

Background:
The prognostic implications of biomarker elevation following percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions remain controversial. This study assessed the association of periprocedural myocardial injury and clinically relevant definition of periprocedural myocardial infarction with subsequent outcomes after CTO-PCI.

Methods:
We enrolled consecutive patients between January 2010 and December 2013 who underwent CTO-PCI at a large-volume center with serial CK-MB (creatine kinase–myocardial band) or cTnI (cardiac troponin I) measurements. The primary outcome was 5-year cardiovascular death.

Results:
A total of 2616 patients (2691 CTOs) with postprocedural CK-MB or cTnI undergoing PCI recanalization were included, per-lesion technical success rate was 74.4%. Postprocedural CK-MB and cTnI elevation occurred in 5.6% and 65.5% patients, respectively. For 2485 patients with serial CK-MB measurements, only postprocedural peak CK-MB ≥5× upper reference limit was associated with increased 5-year cardiovascular death (adjusted hazard ratio, 9.88 [95% CI, 3.06–31.9]). In contrast, for 1233 patients with serial cTnI measurements, no such association was present in any threshold. The Society for Cardiovascular Angiography and Interventions definition of periprocedural myocardial infarction was associated with 5-year cardiovascular death (adjusted hazard ratio, 8.45 [95% CI, 3.58–20.0]), whereas the ARC-2 (Academic Research Consortium-2) and fourth UDMI (Universal Definition of Myocardial Infarction) were not.

Conclusions:
In a large cohort of CTO-PCI, moderate to high levels of peak postprocedural CK-MB were prognostically significant, whereas such association was not observed in postprocedural cTnI. The Society for Cardiovascular Angiography and Intervention criteria (but not ARC-2 and fourth UDMI) were identified as clinically relevant periprocedural myocardial infarction definition following CTO-PCI.

Graphic Abstract:

A
graphic abstract
is available for this article.
The Second International Electrography and Copy Art Biennial, Valencia, Spain, 1988: The Beginning of the Digital Graphics Age
Authors: Alcalá-Mellado José-Ramón 
Published: October 2021

Abstract
In the late 1980s, the commercialization of digital reproduction technology led copy art in a new direction, ushering in a new era of events with global impact and significance. Among these events was the second International Electrography and Copy Art Biennial, held in Valencia, Spain, in October 1988, which commemorated the 50th anniversary of the first electrophotographic copy. This landmark occasion marked the beginning of a new and prosperous digital era that would continue throughout the following decade and was spearheaded by artists of the so-called third generation.
Support needs and barriers to accessing support: Baseline results of a mixed-methods national survey of people bereaved during the COVID-19 pandemic
Authors: Harrop Emily , Goss Silvia , Farnell Damian , Longo Mirella , Byrne Anthony , Barawi Kali , Torrens-Burton Anna , Nelson Annmarie , Seddon Kathy , Machin Linda , Sutton Eileen , Roulston Audrey , Finucane Anne , Penny Alison , Smith Kirsten V , Sivell Stephanie , Selman Lucy E 
Published: October 2021

Background: The COVID-19 pandemic is a mass bereavement event which has profoundly disrupted grief experiences. Understanding support needs and access to support among people bereaved at this time is crucial to ensuring appropriate bereavement support infrastructure. Aim: To investigate grief experiences, support needs and use of formal and informal bereavement support among people bereaved during the pandemic. Design: Baseline results from a longitudinal survey. Support needs and experiences of accessing support are reported using descriptive statistics and thematic analysis of free-text data. Setting/participants: 711 adults bereaved in the UK between March and December 2020, recruited via media, social media, national associations and community/charitable organisations. Results: High-level needs for emotional support were identified. Most participants had not sought support from bereavement services (59%, n = 422) or their General-Practitioner (60%, n = 428). Of participants who had sought such support, over half experienced difficulties accessing bereavement services (56%, n = 149)/General-Practitioner support (52%, n = 135). About 51% reported high/severe vulnerability in grief; among these, 74% were not accessing bereavement or mental-health services. Barriers included limited availability, lack of appropriate support, discomfort asking for help and not knowing how to access services. About 39% ( n = 279) experienced difficulties getting support from family/friends, including relational challenges, little face-to-face contact and disrupted collective mourning. The perceived uniqueness of pandemic bereavement and wider societal strains exacerbated their isolation. Conclusions: People bereaved during the pandemic have high levels of support needs alongside difficulties accessing support. We recommend increased provision and tailoring of bereavement services, improved information on support options and social/educational initiatives to bolster informal support and ameliorate isolation.
Lung metastasectomy for osteosarcoma in children, adolescents, and young adults: proof of permanent cure
Authors: Pastorino Ugo , Palmerini Emanuela , Porcu Luca , Luksch Roberto , Scanagatta Paolo , Meazza Cristina , Leuzzi Giovanni , Massimino Maura , Picci Piero 
Published: October 2021

Introduction Surgical resection of pulmonary metastases has been associated with increased survival at 5 years for osteosarcoma, but limited information is available on long-term outcome, role of repeated metastasectomies, and surgical sequelae in a pediatric population. We analyzed a consecutive series of children, adolescents, and young adults (AYA) treated by repeated lung metastasectomies during a period >40 years to estimate the clinical benefit and potential cure rate of salvage surgery. Methods All patients who underwent lung metastasectomy for osteosarcoma at the IRCCS Istituto Ortopedico Rizzoli of Bologna, University of Modena, and IRCCS Istituto Nazionale Tumori of Milan from May 1973 to January 2014 were included. Overall survival (OS) at 20 years from the first metastasectomy was calculated. Results A total of 463 consecutive children and AYA were analyzed. Median age was 15.9 years (range 0.2–23.2 years) and median follow-up 18.6 years. The 5- and 20-year OS were 34.0% and 29.7% (95% CI 25.5–34.0%). Among the 138 (29.8%) alive patients, 42 (30.4%) had disease recurrence cured by repeated metastasectomies. Disease-free interval from primary tumor, number of metastases, and complete resection were the most relevant survival predictors at multivariable model analysis. Discussion The extended follow-up of this consecutive series shows that repeated lung metastasectomy can achieve a permanent cure when offered to properly selected patients with metastases from osteosarcoma.
Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?
Authors: Napolitano Sara , Ottaviano Giorgio , Bettini Laura , Russotto Vincenzo , Bonanomi Sonia , Rovelli Attilio , Biondi Andrea , Rona Roberto , Balduzzi Adriana 
Published: October 2021

Background: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. Methods In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. Results: CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported ( p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. Conclusion: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.
Current demand and supply of impact investments across different geographic regions, sectors, and stages of business: Match or mismatch?
Authors: Islam Syrus M , Scott Tom 
Published: October 2021

We examine the match/mismatch between the demand and supply of impact investments. We show that some geographic regions display an upward match, while others exhibit a downward match. We explain how regions with well-developed (or less-developed) economies are not necessarily equal to regions with well-developed (or less-developed) impact investment markets. We also highlight the sectors exhibiting a match or mismatch between the demand and supply of investments, and explain the potential reasons. Regarding both geographic and sector concentration, the demand for investments is much more concentrated than their supply. Finally, early-stage companies suffer from an undersupply of investments, while growth-stage companies display an upward match and mature companies have an oversupply of investments. These findings have implications for impact investing theory and practice, including the attainment of Sustainable Development Goals.JEL Classification: D53; E41; E51; G15; G23