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Epistemological issues associated with Cantorian set theory were at the center of the foundational debates from 1900 onward. Hermann Weyl, as a central actor, saw this as a smoldering crisis that burst into flames after World War I. The historian Herbert Mehrtens argued that this “foundations crisis” was part of a larger conflict that pitted moderns, led by David Hilbert, against various counter-moderns, who opposed the promotion of set theory and trends toward abstract theories. Among counter-moderns, L.E.J. Brouwer went a step further by proposing new foundational principles based on his philosophy of intuitionism. Meanwhile, Felix Hausdorff emerged as a leading proponent of the new modern style. In this essay, I offer a reassessment of the foundations crisis that stresses the marginal importance of the various intellectual issues involved. Instead, I offer an interpretation that focuses on tensions within the German mathematical community that led to a dramatic power struggle for control of the journal Mathematische Annalen.
In approaching ‘Invariante Variationsprobleme’ as a contribution to mathematical physics (which it undeniably was), one might easily regard it as a singularity within Noether’s corpus of collected works. This impression quickly dissipates, however, if one shifts the focus to the mathematical methods she employed. Beyond Lie’s theory of differential equations, Noether also made use of formal methods in the calculus of variations, ideas first set forth by Riemann and Lipschitz. This chapter shows the importance of these methods for understanding Noether’s broader agenda in 1917-18. It highlights two competing approaches to the study of differential invariants before, during, and after the advent of Einstein’s general theory of relativity. Noether’s expertise in invariant theory made her an ideal assistant to Felix Klein in his explorations of older literature relating to the mathematical foundations of special and general relativity. Klein argued that Christoffel’s purely algebraic methods for deriving differential invariants were essentially inferior to those based on formal variational methods. The former-as championed by Ricci and later taken up by Grossmann and Einstein-thus stood in opposition to Noether’s work from this period.
Studies of thalamic structure and function in Progressive Supranuclear Palsy (PSP) suggest it may play a role in key aspects of the clinical syndrome. This study examined thalamic changes across PSP phenotypes investigating (i) thalamic atrophy (ii) thalamic functional connectivity and (iii) the relationship between thalamic structural and functional connectivity changes with clinical severity.
Methods
Participants
92 participants with PSP [63 PSP-Richardson's Syndrome (RS), 24 PSP-cortical, 5 PSP-subcortical] and 104 age-matched controls were recruited from the Cambridge Centre for Parkinson's Plus Disorders cohort. Clinical assessments and imaging were conducted within 1 year of diagnosis.
Structural Analysis
Thalamic volumes (TVs) were obtained using FreeSurfer. Bayesian multiple regression (brms, R) was used to model (i) mean TVs (ii) group differences in mean TVs (iii) relationships between Z-standardised clinical scores and TVs with age, gender, and total grey matter as covariates.
Functional Analysis
Voxel-wise seed-based functional connectivity of the thalamus used the Functional Magnetic Resonance Imaging Expert Analysis Tool (FEAT) in FMRIB's Software Library (FSL). Inter-group differences and relationships between clinical scores and functional connectivity for each group were assessed using a general linear model with age and gender as covariates.
Results
Structural Analysis
TVs for all PSP subgroups were smaller than controls. No differences between PSP subgroups were detected. There was evidence for a relationship between TVs for the entire PSP group and Revised Addenbrooke's Cognitive Examination (ACER) scores [ß = 0.28, 95% credible interval (CI) = 0.04–0.53]. Subgroup analysis showed evidence for a relationship between ACER scores and TVs in PSP-RS [ß = 0.33, 95% CI = 0.09–0.57] and PSP-cortical [ß = 0.46, 95% CI = 0.12–0.83] phenotypes. A negative influence of TVs on total PSP rating scale scores was found for the PSP cohort a whole [ß = −0.51, 95% CI = −1.00 – −0.02].
Functional Analysis
PSP patients as a group showed decreased thalamic functional connectivity in higher cortical regions. Subgroup analysis revealed decreased connectivity in those areas compared to controls but in distinct distributions and magnitude. Increased thalamic connectivity with the middle temporal gyrus correlated with ACER scores for PSP patients as a group and in the PSP-cortical subtype.
Conclusion
Thalamic volume loss is a prominent aspect of PSP and is associated with a wide network of changes in functional connectivity that may be distinct between PSP subtypes. Changes in thalamic structure and function predict clinical severity, particularly in PSP-RS and PSP-cortical subtypes.
Antibiotics are frequently prescribed in nursing homes; national data describing facility-level antibiotic use are lacking. The objective of this analysis was to describe variability in antibiotic use in nursing homes across the United States using electronic health record orders.
Methods:
A retrospective cohort study of antibiotic orders for 309,884 residents in 1,664 US nursing homes in 2016 were included in the analysis. Antibiotic use rates were calculated as antibiotic days of therapy (DOT) per 1,000 resident days and were compared by type of stay (short stay ≤100 days vs long stay >100 days). Prescribing indications and the duration of nursing home-initiated antibiotic orders were described. Facility-level correlations of antibiotic use, adjusting for resident health and facility characteristics, were assessed using multivariate linear regression models.
Results:
In 2016, 54% of residents received at least 1 systemic antibiotic. The overall rate of antibiotic use was 88 DOT per 1,000 resident days. The 3 most common antibiotic classes prescribed were fluoroquinolones (18%), cephalosporins (18%), and urinary anti-infectives (9%). Antibiotics were most frequently prescribed for urinary tract infections, and the median duration of an antibiotic course was 7 days (interquartile range, 5–10). Higher facility antibiotic use rates correlated positively with higher proportions of short-stay residents, for-profit ownership, residents with low cognitive performance, and having at least 1 resident on a ventilator. Available facility-level characteristics only predicted a small proportion of variability observed (Model R2 version 0.24 software).
Conclusions:
Using electronic health record orders, variability was found among US nursing-home antibiotic prescribing practices, highlighting potential opportunities for targeted improvement of prescribing practices.
Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug–drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.
Despite the substantial investment by Australian health authorities to improve the health of rural and remote communities, rural residents continue to experience health care access challenges and poorer health outcomes. Health literacy and community engagement are both considered critical in addressing these health inequities. However, the current focus on health literacy can place undue burdens of responsibility for healthcare on individuals from disadvantaged communities whilst not taking due account of broader community needs and healthcare expectations. This can also marginalize the influence of community solidarity and mobilization in effecting healthcare improvements.
Objective:
The objective is to present a conceptual framework that describes community literacy, its alignment with health literacy, and its relationship to concepts of community engaged healthcare.
Findings:
Community literacy aims to integrate community knowledge, skills and resources into the design, delivery and adaptation of healthcare policies, and services at regional and local levels, with the provision of primary, secondary, and tertiary healthcare that aligns to individual community contexts. A set of principles is proposed to support the development of community literacy. Three levels of community literacy education for health personnel have been described that align with those applied to health literacy for consumers. It is proposed that community literacy education can facilitate transformational community engagement. Skills acquired by health personnel from senior executives to frontline clinical staff, can also lead to enhanced opportunities to promote health literacy for individuals.
Conclusions:
The integration of health and community literacy provides a holistic framework that has the potential to effectively respond to the diversity of rural and remote Australian communities and their healthcare needs and expectations. Further research is required to develop, validate, and evaluate the three levels of community literacy education and alignment to health policy, prior to promoting its uptake more widely.
The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
Methods:
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Results:
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Conclusions:
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
Little is known about the social and emotional well-being of children whose fathers have been deployed to the conflicts in Iraq/Afghanistan or who have post-traumatic stress disorder (PTSD).
Aims
To examine the emotional and behavioural well-being of children whose fathers are or have been in the UK armed forces, in particular the effects of paternal deployment to the conflicts in Iraq or Afghanistan and paternal PTSD.
Method
Fathers who had taken part in a large tri-service cohort and had children aged 3–16 years were asked about the emotional and behavioural well-being of their child(ren) and assessed for symptoms of PTSD via online questionnaires and telephone interview.
Results
In total, 621 (67%) fathers participated, providing data on 1044 children. Paternal deployment to Iraq or Afghanistan was not associated with childhood emotional and behavioural difficulties. Paternal probable PTSD were associated with child hyperactivity. This finding was limited to boys and those under 11 years of age.
Conclusions
This study showed that adverse childhood emotional and behavioural well-being was not associated with paternal deployment but was associated with paternal probable PTSD.
Declaration of interest
N.T.F. is a trustee of the Warrior Programme, a charity supporting ex-service personnel and their families. She is also a member of the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee of Combat Stress, a charity supporting ex-service personnel and their families, and President of the Royal Society of Medicine. S.W. is partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England (PHE), in collaboration with the University of East Anglia and Newcastle University.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
Aims
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Method
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
Results
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
Conclusions
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Methods:
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
Results:
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
Conclusion:
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
Although procedural sedation for cardioversion is a common event in emergency departments (EDs), there is limited evidence surrounding medication choices. We sought to evaluate geographic and temporal variation in sedative choice at multiple Canadian sites, and to estimate the risk of adverse events due to sedative choice.
Methods
This is a secondary analysis of one health records review, the Recent Onset Atrial Fibrillation or Flutter-0 (RAFF-0 [n=420, 2008]) and one prospective cohort study, the Recent Onset Atrial Fibrillation or Flutter-1 (RAFF-1 [n=565, 2010 – 2012]) at eight and six Canadian EDs, respectively. Sedative choices within and among EDs were quantified, and the risk of adverse events was examined with adjusted and unadjusted comparisons of sedative regimes.
Results
In RAFF-0 and RAFF-1, the combination of propofol and fentanyl was most popular (63.8% and 52.7%) followed by propofol alone (27.9% and 37.3%). There were substantially more adverse events in the RAFF-0 data set (13.5%) versus RAFF-1 (3.3%). In both data sets, the combination of propofol/fentanyl was not associated with increased adverse event risk compared to propofol alone.
Conclusion
There is marked variability in procedural sedation medication choice for a direct current cardioversion in Canadian EDs, with increased use of propofol alone as a sedation agent over time. The risk of adverse events from procedural sedation during cardioversion is low but not insignificant. We did not identify an increased risk of adverse events with the addition of fentanyl as an adjunctive analgesic to propofol.
The growth of speleothems is indicative of interglacial and interstadial conditions in the United Kingdom, since their growth is dependent on two factors. First, the occurrence of significant diffuse groundwater recharge and, second, the biogenic production of carbon dioxide in the soil, both are dependent on temperature and water availability. The growth frequency of speleothems is examined using a cumulative distributed error frequency method applied to 341 uncontaminated uranium-series age determinations. The curves derived are shown to be statistically stable, and the ages of the peaks are interpreted as the best estimates of the ages of interglacial and interstadial periods. Ten such periods are recognized during the interval 220,000 to 20,000 yr B.P., considerably more than are currently recognized in the UK pollen- and coleoptera-based Quaternary stratigraphy. Correlations between the speleothem growth frequency peaks and last interglacial (Ipswichian) sites can be made, but correlations with last glacial (Devensian) interstadial sites are limited because of the paucity of dates. The speleothem growth frequency record provides a well-dated terrestrial chronology for the past 140,000 yr B.P., which directly reflects regional palaeoclimatic conditions in Britain, and should prove very useful in unravelling the complex stratigraphy of the Devensian and Ipswichian stages.
Chronic disease, mobility limitations and low physical functioning are determinants of an earlier age of retirement. Therefore, long-term population trends in these factors may have an impact on the proportion of individuals near traditional retirement age who continue to work. Our objective is to develop a projection model that accounts for trends in these factors in order to estimate the proportion of the population aged 55–74 with the capacity to participate in the labour force. We used logistic regression models to quantify how chronic disease, mobility and functional status predict labour force participation among individuals aged 55–59. Next, we obtained estimates of the population prevalence of each of these predictors for the years 2010–2050. We then used estimated coefficients from the logistic regression models to predict the age-specific probability of capacity for work up to the age of 74. We find that population capacity for work depends on trends in disability and on level of education. Future population capacity for work depends on trends in functional limitations primarily in the population with lower levels of education. Changes in functional limitations, changes in the environment, technology and social policy targeted towards individuals with lower levels of education could result in mitigation of future decreasing capacity for work in the population near retirement age.
We conducted a program of research to derive and test the reliability of a clinical prediction rule to identify high-risk older adults using paramedics’ observations.
Methods
We developed the Paramedics assessing Elders at Risk of Independence Loss (PERIL) checklist of 43 yes or no questions, including the Identifying Seniors at Risk (ISAR) tool items. We trained 1,185 paramedics from three Ontario services to use this checklist, and assessed inter-observer reliability in a convenience sample. The primary outcome, return to the ED, hospitalization, or death within one month was assessed using provincial databases. We derived a prediction rule using multivariable logistic regression.
Results
We enrolled 1,065 subjects, of which 764 (71.7%) had complete data. Inter-observer reliability was good or excellent for 40/43 questions. We derived a four-item rule: 1) “Problems in the home contributing to adverse outcomes?” (OR 1.43); 2) “Called 911 in the last 30 days?” (OR 1.72); 3) male (OR 1.38) and 4) lacks social support (OR 1.4). The PERIL rule performed better than a proxy measure of clinical judgment (AUC 0.62 vs. 0.56, p=0.02) and adherence was better for PERIL than for ISAR.
Conclusions
The four-item PERIL rule has good inter-observer reliability and adherence, and had advantages compared to a proxy measure of clinical judgment. The ISAR is an acceptable alternative, but adherence may be lower. If future research validates the PERIL rule, it could be used by emergency physicians and paramedic services to target preventative interventions for seniors identified as high-risk.
To assess the ease and reliability of routine use of somatosensory evoked potentials (SSEPs) for identification of sensorimotor cortex in brain tumour removal and to document its influence on the performance and outcome of surgery.
Methods:
SSEPs in response to contralateral median nerve stimulation were recorded from the cortical surface by means of a four lead electrode strip. Polarity reversal of short latency SSEP waves was used to identify the position of the central sulcus in 46 consecutive craniotomies for removal of metastases, gliomas, or meningiomas located in, near, or overlying sensorimotor cortex.
Results:
SSEPs were successfully recorded in 43/46 cases (94%) with demonstration of polarity reversal in 42/43 (98%). SSEP localization led to modification of 14/42 (33%) procedures, most frequently because of either displacement or involvement of sensorimotor cortex by tumour. Six patients (14%) developed new neurological deficits but none of these was attributable to incorrect identification of sensorimotor cortex.
Conclusions:
SSEP polarity reversal is a simple, reliable, accurate, and inexpensive method of localizing sensorimotor cortex under general anaesthesia. Correct identification is possible when sensorimotor cortex is displaced or when surface anatomy is obscured by tumour. Routine use of this technique should be considered in all procedures for lesions located near the central sulcus.
FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants’ nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.
Although many types of sports and recreational activities have been identified as common causes of acute spinal cord injury, hockey has been a rare cause of acute cord injury in Canada or elsewhere. For example, from 1948 to 1973 there were no patients with cord injuries due to hockey in a series of 55 patients with acute cord injuries due to sports or other recreational activities admitted to two Toronto hospitals. In contrast, between 1974 and 1981, the Acute Spinal Cord Injury Unit, Sunnybrook Medical Centre treated six patients with cervical spinal injury due to hockey, five of whom were seen during a 13 month period from September, 1980 to October, 1981. Five of the six sustained a severe acute cervical spinal cord injury, and one a cervical root injury. The cord injury was complete in two cases, while three had complete motor loss but incomplete sensory loss below the level of the lesion. All were males aged 15 to 26 years. Of the players with cord injury, four struck the boards with the neck flexed, and one struck another player with the neck flexed. The one player without cord injury struck the boards with his neck extended. The commonest bony injury was a burst fracture of C5 or C6. One of the patients with a complete cord injury died three months later of a pulmonary embolus, and the other patients with cord injury showed some recovery of root function, but little or no cord recovery. The reasons for the increase in spinal injuries in hockey are unknown.
Regional cerebral blood flow (rCBF) during internal carotid artery (ICA) occlusion for endarterectomy can be measured without inconvenience using the probe holder illustrated.
When mean ipsilateral hemispheric CBF exceeds 20 ml/100 gm/min, an intraluminal bypass is not necessary (63% of patients), except in patients with extensive cerebrovascular disease in whom rCBF should also exceed 20 ml/100 gm/min in all areas. ICA “stump” pressure is falsely high in about 20% of patients, and is therefore not a dependable criterion for selecting patients who need shunting.
While intraoperative shunting is capable of restoring pre-occlusion CBF levels, it does not eliminate the risk of intraoperative ischemic neurological deficit of probable embolic origin.
False aneurysm of the intracranial arteries occurs infrequently as a complication of head injury and rarely as a consequence of other pathology. A case of false aneurysm of the supraclinoid internal carotid artery following minor intraoperative injury during clipping of a basilar-superior cerebellar aneurysm by the pterional approach is described. False aneurysm is a potential cause of recurrent intracranial hemorrhage after successful aneurysm clipping. Arterial bleeding which appears to come from the region of a branch origin should be viewed with concern even if it subsides spontaneously.