Science as a calling and as a profession: The wider setting in Weber's scholarly endeavor.

In his 1917 lecture for Munich students (most often entitled in English translation "Science as a Vocation"), Max Weber addressed numerous issues: not only how "profession" and "calling" are related in science and scholarship, but also Entzauberung ("disenchantment"); rationality and its limits; ultimate values; and the field of tension between science and religion. The present essay locates these themes in Weber's oeuvre from 1911 onward, and analyses how they resonate and culminate in Weber's address in 1917. It is in 1911 that he decided to engage with the problem that was to stand central in his thinking until his death in 1920: the nature and causes of certain specific turns in the course of European history which, so he argued, have proven to be of "universal significance." Special attention is given in the present essay to how Weber dealt in this connection with the rise of modern science and the rise of modern tonal harmony. A concluding section explains what, over a century later, makes reading Weber still so rewarding an experience.

A Systematic Review of Live Animal Use as a Simulation Modality ("Live Tissue Training") in the Emergency Management of Trauma.

INTRODUCTION: Live anaesthetized animals are used as simulation models to teach techniques in the emergency management of trauma. We aimed to explore how "live tissue training" (LTT) is designed, delivered and evaluated in order to better understand and characterize aspects of educational merit. METHODS: A systematic review was performed using PRISMA guidance. A combined approach, involving a 3-stage modified narrative synthesis process and reflexive thematic analysis was used to identify key concepts across the published literature. FINDINGS: Qualitative synthesis of 48 selected articles suggests that LTT is mainly used to teach military and civilian physicians and military medical technicians. The procedures trained vary with the learner population, from simple pre-hospital trauma tasks to advanced operative surgical skills. Many courses use a combination of didactic and practical training, with an animal model used to train practical application of knowledge and procedural skills. Descriptions of the learning interventions are limited, and explicit use of educational theory or pedagogic frameworks were absent within the literature. Four themes were identified regarding aspects of LTT that are valued by learners: "recreating the experience," relating to fidelity and realism; "tick tock" "dynamics of hemorrhage", encompassing the impact of bleeding and urgent pressure to act; "emotional impact" of conducting the training, and "self-efficacy: I believe I can do it." CONCLUSION: Thematic analysis of published literature suggests that there may be educational benefit in the use of live tissue models due to time criticality and bleeding, which creates a real-life event. LTT also invokes an emotional response, and learners experience an increase in self-efficacy from participation. We consider that these aspects and associated pedagogy should be addressed when researching and developing alternative simulation modalities, in order to intelligently replace, reduce and refine the use of animals in training practitioners in the emergency management of trauma.

Neuro-psychiatric symptoms in directly and indirectly blast exposed civilian survivors of urban missile attacks.

BACKGROUND: Blast-explosion may cause traumatic brain injury (TBI), leading to post-concussion syndrome (PCS). In studies on military personnel, PCS symptoms are highly similar to those occurring in post-traumatic stress disorder (PTSD), questioning the overlap between these syndromes. In the current study we assessed PCS and PTSD in civilians following exposure to rocket attacks. We hypothesized that PCS symptomatology and brain connectivity will be associated with the objective physical exposure, while PTSD symptomatology will be associated with the subjective mental experience. METHODS: Two hundred eighty nine residents of explosion sites have participated in the current study. Participants completed self-report of PCS and PTSD. The association between objective and subjective factors of blast and clinical outcomes was assessed using multivariate analysis. White-matter (WM) alterations and cognitive abilities were assessed in a sub-group of participants (n = 46) and non-exposed controls (n = 16). Non-parametric analysis was used to compare connectivity and cognition between the groups. RESULTS: Blast-exposed individuals reported higher PTSD and PCS symptomatology. Among exposed individuals, those who were directly exposed to blast, reported higher levels of subjective feeling of danger and presented WM hypoconnectivity. Cognitive abilities did not differ between groups. Several risk factors for the development of PCS and PTSD were identified. CONCLUSIONS: Civilians exposed to blast present higher PCS/PTSD symptomatology as well as WM hypoconnectivity. Although symptoms are sub-clinical, they might lead to the future development of a full-blown syndrome and should be considered carefully. The similarities between PCS and PTSD suggest that despite the different etiology, namely, the physical trauma in PCS and the emotional trauma in PTSD, these are not distinct syndromes, but rather represent a combined biopsychological disorder with a wide spectrum of behavioral, emotional, cognitive and neurological symptoms.

Potential for Anthropogenic Fin Damage to Affect Individual Responses to Prey in Bluegill Sunfish (Lepomis macrochirus): A New Hypothesis for Kinematic Studies.

In fishes, damage to important morphological structures such as fins through natural damage and anthropogenic factors can have cascading effects on prey capture performance and individual fitness. Bluegill sunfish (Lepomis macrochirus) are a common freshwater species in North America, are a model organism for performance studies, and often experience natural injuries. We opportunistically sampled two populations of fish in the lab to generate a hypothesis for the effect of sub-lethal fin damage resulting from the capture technique on kinematic performance during prey capture in bluegill. We found no statistical differences in mean prey capture kinematics or predator accuracy, but damaged fish used more variable kinematics and more readily struck at non-prey items. We suggest that a reduction in stability and individual consistency occurs as a result of fin damage. This difference could have consequences for higher-order ecological interactions such as competitive ability, despite a lack of apparent performance cost at the individual level, and deserves consideration in future studies of prey capture performance in fish.

Features of the metabolic syndrome and subclinical atherosclerosis in patients with cerebrotendinous xanthomatosis: An augmented risk for premature cardiovascular disease.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disease, caused by deficiency of sterol-27-hydroxylase. Xanthomatous lesions in numerous tissues, and an elevation of cholestanol levels, characterize the disease. Its natural course is progressive neurologic deterioration, leading to premature death. Chronic treatment with oral chenodeoxycholic acid (CDCA) reduces cholestanol levels. Occurrence of premature atherosclerosis has been described in CTX in an unknown mechanism. Aim: The aim of the current work was to evaluate the potential metabolic abnormalities and preclinical vascular changes in Israeli CTX patients. Methods: Ten subjects with CTX were studied. Features of the metabolic syndrome were evaluated, and carotid intima media thickness (cIMT) was measured in the common carotid arteries. Results: All patients were diagnosed with CTX, and all received treatment with CDCA, which resulted in normalization of their plasma cholestanol levels. At the conclusion of the follow up, risk factors for CVD and features of MS were present in all the patients and in three patients, cIMT was higher compared to control subjects. Conclusion: Cardiovascular risk factors and premature vascular changes exist in young CTX patients and proper assessment should be implemented with preventive measures to reduce the risk of atherosclerotic cardiovascular disease in CTX patients.

The effect of α-linolenic acid enrichment in perinatal diets in preventing high fat diet-induced SCD1 increased activity and lipid disarray in adult offspring of low density lipoprotein receptor knockout (LDLRKO) mice.

The present study examined the effects of maternal perinatal dietary ALA enrichment on the high fat diet (HFD)-induced lipid disarray in the adult offspring of low density lipoprotein receptor knock-out (LDLRKO) mice. Female LDLRKO mice received, during pregnancy and lactation, isocaloric diets with either corn oil, RD, or flax oil, ALA. The weaning offspring was given a regular chow diet for a washout period of eight weeks, which was followed by HFD for eight weeks. Plasma and liver lipids and SCD1 activity were then analyzed. The HFD-fed RD adult offspring had substantially higher plasma cholesterol levels than the HFD-fed ALA offspring (15.7 versus 9.7 mmole/l, p<0.00001) and non-alcoholic fatty liver disease (NAFLD) (65.0 versus 23.9 mg/g lipids, p<0.00001). Liver lipids oleic acid (OA) content and monounsaturated to saturated fatty acids (MUFA/SAT) ratio, were two times lower in RD compared to ALA (p<0.0001). The threefold HFD-induced SCD1 raised activity (p<0.00001), and OA produced from SA, observed in RD adult offspring were prevented by perinatal ALA. In conclusion, the resilience of SCD1 to HFD- induced increased activity may account for the beneficial effects of perinatal ALA dietary enrichment in preventing NAFLD and hypercholesterolemia from occurring in adult LDLRKO offspring mice.

Bringing damage control surgery simulation to life: developing a novel surgical anatomy model within immersive military trauma surgery simulation.

Haemorrhage from junctional injuries remains the most common cause of battlefield death. Changes to surgical training have meant acquiring and maintaining trauma surgical skills is becoming more difficult for military surgeons. The multidisciplinary Military Operational Specialist Team Training (MOSTT) course is designed to bridge the gap between civilian practice and the deployed environment, as part of predeployment trauma training. It involves immersive team simulation and uses cadaveric dissection for surgical skills practice.A novel surgical anatomy model, featuring junctional haemorrhage surgical task trainers of the groin and shoulder, was designed using reconstructed CT and MRI images obtained from a human volunteer. The model is designed to look and feel as realistic as possible, with the added dimension of pulsatile 'blood' flow from a simulation gunshot injury.This surgical anatomy model has been trialled, as part of the MOSTT course, by 90 surgeons and perioperative practitioners, with feedback analysis used for iterative model development. Feedback demonstrated that, alongside more traditional cadaveric dissection, this surgical anatomy model adds value to current predeployment training delivered within the immersive simulation of the MOSTT course. Research by the authors about the effects of this model on surgical ability and performance is ongoing. However, there is clear potential for this model to be used in other environments, including on exercises and as part of consolidation training while deployed.

Chemistry and Charge Trapping at the Interface of Silver and Ultrathin Layers of Zinc Oxide.

Zinc oxide, a wide-band-gap semiconductor, shows intriguing optoelectronic properties when coupled with Ag. Specifically, an absorbance band in the visible range that is not apparent in the separated materials emerges when the interface is formed. Interestingly, photoexcitation of this "interface band" or band-to-band results in a counterintuitive photovoltaic response when a supra/sub-band-gap light is shone. To investigate the origin of this absorbance band and photovoltaic response, we studied in detail the energy-band alignment of ultrathin layers of ZnO (3-60 nm) with Ag. Our analysis indicated that an 'electrostatic potential cliff' is formed within the first 1-2 nm of ZnO. In addition, oxygen vacancies, presumably generated by AgxO-Zn bonds, form mid-gap acceptor states within these first few nm. Both effects facilitate a valence band-to-defect state optical transition that is confined to the interface region. The second type of defects-hole-trap states associated with zinc hydroxide-are spread throughout the ZnO layer and dominate the supra-band-gap photovoltaic response. These findings have potential implications in emerging technologies such as photocatalytic Ag/ZnO heterostructures that will utilize the long-lived charges for chemical work or other optoelectronic applications.

Medical care disruptions during the first six months of the COVID-19 pandemic: the experience of older breast cancer survivors.

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.

Restoration of energy homeostasis by SIRT6 extends healthy lifespan.

Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.

Medical Care Disruptions During the First Six-Months of the COVID19 Pandemic: The Experience of Older Breast Cancer Survivors.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. RESULTS: There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. CONCLUSIONS: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

[Maternal mortality by stroke in France 2013-2015]. / Mortalité maternelles par accident vasculaire cérébrale en France 2013­2015.

Between 2013 and 2015, 20 maternal deaths were associated with stroke. Stroke was the main cause of death in 16 cases (12 hemorrhagic strokes [75%], 1 ischemic stroke and three cerebral thrombophlebitis). In the four other cases, the stroke was a complication of another pathology. The 16 deaths directly related to stroke account for 5.7% of all maternal deaths (maternal mortality ratio of 0.7/100,000 live births vs. 0.9/100,000 over the period 2010-2012, NS). Stroke occurred during pregnancy in 8 cases (50%). Three patients died without giving birth and the 5 others gave birth by emergency caesarean section. In the remaining eight cases (50%), stroke occurred between day 0 and day 54 during the post-partum period. The mean age was 35.5 years, with 9 women being more than 35 years old (56%). One or more factors of sub-optimal care were present in 28% of the cases, and 8% of deaths were considered possibly or probably preventable. The last four strokes were associated with another pathology (eclampsia [n=2], hepatic cirrhosis [n=1], possible complication of spinal anesthesia [n=1]).

Baseline factors associated with early and late death in intracerebral haemorrhage survivors.

BACKGROUND AND PURPOSE: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. METHODS: This was a secondary analysis of the multicentre prospective observational CROMIS-2 ICH study. Death was defined as 'early' if occurring within 6 months of study entry and 'late' if occurring after this time point. RESULTS: In our cohort (n = 1094), there were 306 deaths (per 100 patient-years: absolute event rate, 11.7; 95% confidence intervals, 10.5-13.1); 156 were 'early' and 150 'late'. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre-event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre-event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. CONCLUSIONS: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH.

Race/Ethnic and Educational Disparities in the Association Between Pathogen Burden and a Laboratory-Based Cumulative Deficits Index.

BACKGROUND: Disparities in adult morbidity and mortality may be rooted in patterns of biological dysfunction in early life. We sought to examine the association between pathogen burden and a cumulative deficits index (CDI), conceptualized as a pre-clinical marker of an unhealthy biomarker profile, specifically focusing on patterns across levels of social disadvantage. METHODS: Using the data from the National Health and Nutrition Examination Survey 2003-2004 wave (aged 20-49 years), we examined the association of pathogen burden, composed of seven pathogens, with the CDI. The CDI comprised 28 biomarkers corresponding to available clinical laboratory measures. Models were stratified by race/ethnicity and education level. RESULTS: The CDI ranged from 0.04 to 0.78. Nearly half of Blacks were classified in the high burden pathogen class compared with 8% of Whites. Among both Mexican Americans and other Hispanic groups, the largest proportion of individuals were classified in the common pathogens class. Among educational classes, 19% of those with less than a high school education were classified in the high burden class compared with 7% of those with at least a college education. Blacks in the high burden pathogen class had a CDI 0.05 greater than those in the low burden class (P < 0.05). Whites in the high burden class had a CDI only 0.03 greater than those in the low burden class (P < 0.01). DISCUSSION: Our findings suggest there are significant social disparities in the distribution of pathogen burden across race/ethnic groups, and the effects of pathogen burden may be more significant for socially disadvantaged individuals.

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study.

OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

Association between circulating inflammatory markers and marksmanship following intense military training.

INTRODUCTION: Intense military operations during deployment or training are associated with elevations in inflammatory cytokine markers. However, the influence of an inflammatory response on military-specific skills is unclear. This study examined the association between brain-derived neurotrophic factor (BDNF), glial fibrillar acidic protein, markers of inflammation, marksmanship and cognitive function following a week of intense military field training. METHODS: Twenty male soldiers (20.1±0.6 years; 1.78±0.05m; 74.1±7.9kg) from the same elite combat unit of the Israel Defense Forces volunteered to participate in this study. Soldiers completed a five-day period of intense field training including navigation of 27.8km/day with load carriages of ~50% of their body mass. Soldiers slept approximately fivehours per day and were provided with military field rations. Following the final navigational exercise, soldiers returned to their base and provided a blood sample. In addition, cognitive function assessment and both dynamic and static shooting (15 shots each) were performed following a 200 m gauntlet, in which soldiers had to use hand-to-hand combat skills to reach the shooting range. RESULTS: Results revealed that tumour necrosis factor-α (TNF-α) concentrations were inversely correlated with dynamic shooting (r=-0.646, p=0.005). In addition, a trend (r=0.415, p=0.098) was noted between TNF-α concentrations and target engagement speed (ie, time to complete the shooting protocol). BDNF concentrations were significantly correlated with the Serial Sevens Test performance (r=0.672, p=0.012). CONCLUSION: The results of this investigation indicate that elevated TNF-α concentrations and lower BDNF concentrations in soldiers following intense military training were associated with decreases in marksmanship and cognitive function, respectively.

Calibrating balance perturbation using electrical stimulation of the vestibular system.

BACKGROUND: Supra-threshold galvanic vestibular stimulation (GVS) can be used to challenge the balance control system by disrupting vestibular inputs. The goal of this study was to propose an objective method to assess variability across subjects in the minimum safe GVS level that causes maximum balance degradation. New method: Thirteen healthy young subjects stood on a compliant foam surface with their eyes closed and tried to maintain a stable upright stance. Variables related to the stability of the trunk and whole body were quantified to characterize the relationship between postural responses and GVS at amplitudes from 0 to 4.5 mA in 0.5 mA increments. The relationship between decrements in postural responses and GVS was linear up to a minimum GVS level (called KNEE). An increase in the stimulation level above that did not lead to any further degradation of balance performance. The KNEE was determined by iteratively performing linear fits to the performance measure at different stimulation levels. RESULTS: There were individual differences in KNEE; it was in the range of 1-2.5 mA across subjects. GVS caused an average performance decrement of 27-99% across six variables at the KNEE level compared to a no-stimulus condition. Comparison to existing methods: We propose a method to consistently attain the maximum level of impairment across subjects using the minimum current intensity, to minimize all types of adverse effects usually observed at high intensities. CONCLUSIONS: Individual differences in the disruption of posture control in response to GVS have important implications for testing and training paradigms.

Stock and bulk in the latest Newton scholarship.

In his biography of Isaac Newton, which forms the most recent production in this flourishing genre, Niccolò Guicciardini states as his first point of departure that Newton's work arose not from 'attempts to answer questions that came to him spontaneously, but [from addressing] those posed by his contemporaries' (p. 20). Right he is to communicate to the larger audience for which he is writing this principal fruit of by now almost a century of professional history-of-science writing - a deep-seated awareness that every scientific view or finding, even if looking timeless in retrospect, has emerged from some given historical context that shows us where the scientist in question started, and that helps explain how, and in what direction, they managed to venture beyond the original context. Indeed, the same truth (or rather truism) applies to every genuine - that is, in some way innovative and also worthwhile - contribution to scholarship. And so it is, therefore, with the three books here under review, which I intend to examine with the following leading question in mind: what in each of them is new and what, in what turns out to be new indeed, has been worth learning?

Antibodies against TFPI and protein C are associated with a severe thrombotic phenotype in patients with and without antiphospholipid syndrome.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) antibodies, which have been reported in patients with antiphospholipid syndrome (APS), may impair TFPI activity and contribute to hypercoagulability, but their role in APS and in thrombosis remains undefined. OBJECTIVE/METHODS: We assessed the presence and avidity of TFPI IgG antibodies, associations with protein C IgG antibodies and associations with clinical disease severity, in 50 patients with thrombotic APS and 50 thrombotic control patients, on long term anticoagulation with warfarin. RESULTS: Thrombotic APS patients had a significantly higher prevalence of TFPI IgG antibodies (40%; 20/50) compared to thrombotic controls (18%; 9/50). TFPI antibodies were predominantly high avidity in APS (50%, 10/20 of positive patients) and strongly associated with a severe thrombotic phenotype (venous and arterial thromboembolism or recurrent thromboembolic episodes despite therapeutic anticoagulation) (odds ratio (OR): 12.0, 95%CI: 2.2-66.1, p = 0.004), while thrombotic control patients mainly showed low avidity antibodies (78%, 7/9 of positive patients). Coexistence of TFPI and protein C IgG antibodies, regardless of their avidity, was strongly associated with a more severe thrombotic phenotype in APS patients (OR: 20.2, 95%CI: 2.0-47.0, p < 0.0001) and also in thrombotic controls (OR: 75.0, 95%CI 1.2-195, p = 0.02). CONCLUSIONS: Coexistent TFPI and protein C IgG antibodies, irrespective of their avidity, may be a useful marker for a severe thrombotic phenotype in thrombotic patients. This suggests a possibly pathophysiological relationship between the two antibodies, predisposing to thrombosis with a possibly more general role in the development of thrombotic complications.