Spin and Statistics and First Principles

It was shown in the early Seventies that, in Local Quantum Theory (that is the most general formulation of Quantum Field Theory, if we leave out only the unknown scenario of Quantum Gravity) the notion of Statistics can be grounded solely on the local observable quantities (without assuming neither the commutation relations nor even the existence of unobservable charged field operators); one finds that only the well known (para)statistics of Bose/Fermi type are allowed by the key principle of local commutativity of observables. In this frame it was possible to formulate and prove the Spin and Statistics Theorem purely on the basis of First Principles. In a subsequent stage it has been possible to prove the existence of a unique, canonical algebra of local field operators obeying ordinary Bose/Fermi commutation relations at spacelike separations. In this general guise the Spin - Statistics Theorem applies to Theories (on the four dimensional Minkowski space) where only massive particles with finite mass degeneracy can occur. Here we describe the underlying simple basic ideas, and briefly mention the subsequent generalisations; eventually we comment on the possible validity of the Spin - Statistics Theorem in presence of massless particles, or of violations of locality as expected in Quantum Gravity.Comment: Survey based on a talk given at the Meeting on "Theoretical and experimental aspects of the spin - statistics connection and related symmetries", Trieste, Italy - October 21-25, 200

Smallest detectable change in volume differs between mass flow sensor and pneumotachograph

<p>Abstract</p> <p>Background</p> <p>To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph.</p> <p>Method</p> <p>In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2.</p> <p>Findings</p> <p>The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (<it>p </it>= 0.04), DLCO (in mmol*kPa^-1*min^-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (<it>p </it>= 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (<it>p </it>= 0.04) and DLCO/VA (in mmol*kPa^-1*min^-1*L^-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (<it>p </it>= 0.79).</p> <p>Conclusions</p> <p>Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.</p

Factors associated with disease progression in early-diagnosed pulmonary arterial hypertension associated with systemic sclerosis: longitudinal data from the DETECT cohort

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort. METHODS: Patients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression. RESULTS: Of 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship). CONCLUSION: More than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Depression after low-energy fracture in older women predicts future falls: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Falls are one of the main causes of fractures in elderly people and after a recent fracture, the risk of another fall is increased, resulting in subsequent fracture. Therefore, risk factors for future falls should be determined. We prospectively investigated the relationship between depression and the incidence of falls in post-menopausal women after a low-energy fracture.</p> <p>Methods</p> <p>At baseline, 181 women aged 60 years and older who presented with a recent low-energy fracture were evaluated at the fracture and osteoporosis outpatient clinics of two hospitals. As well as clinical evaluation and bone mineral density tests, the presence of depression (measured using the Edinburgh Depression Scale, EDS, depression cut-off > 11) and risk factors for falling were assessed. During two years of follow-up, the incidence of falls was registered annually by means of detailed questionnaires and interviews.</p> <p>Results</p> <p>Seventy-nine (44%) of the women sustained at least one fall during follow-up. Of these, 28% (<it>n </it>= 22) suffered from depression at baseline compared to 10% (<it>n </it>= 10) of the 102 women who did not sustain a fall during follow-up (<it>Χ</it>²= 8.76, df = 1, <it>p </it>= .003). Multiple logistic regression showed that the presence of depression and co-morbidity at baseline were independently related to falls (OR = 4.13, 95% CI = 1.58-10.80; OR = 2.25, 95% CI = 1.11-4.56, respectively) during follow-up.</p> <p>Conclusions</p> <p>The presence of depression in women aged 60 years and older with recent low-energy fractures is an important risk factor for future falls. We propose that clinicians treating patients with recent low-energy fractures should anticipate not only on skeletal-related risk factors for fractures, but also on fall-related risk factors including depression.</p

Persistently Elevated Right Ventricular Index of Myocardial Performance in Preterm Infants with Incipient Bronchopulmonary Dysplasia

OBJECTIVES: Elevated pulmonary vascular resistance occurs during the first days after birth in all newborn infants and persists in infants at risk for bronchopulmonary dysplasia (BPD). It is difficult to measure in a non-invasive fashion. We assessed the usefulness of the right ventricular index of myocardial performance (RIMP) to estimate pulmonary vascular resistance in very low birth weight infants. STUDY DESIGN: Prospective echocardiography on day of life (DOL) 2, 7, 14, and 28 in 121 preterm infants (median [quartiles] gestational age 28 [26]-[29] weeks, birth weight 998 [743-1225] g) of whom 36 developed BPD (oxygen supplementation at 36 postmenstrual weeks). RESULTS: RIMP derived by conventional pulsed Doppler technique was unrelated to heart rate or mean blood pressure. RIMP on DOL 2 was similar in infants who subsequently did (0.39 [0.33-0.55]) and did not develop BPD (0.39 [0.28-0.51], p = 0.467). RIMP declined steadily in non-BPD infants but not in BPD infants (DOL 7: 0.31[0.22-0.39] vs. 0.35[0.29-0.48], p = 0.014; DOL 14: 0.23[0.17-0.30] vs. 0.35[0.25-0.43], p<0.001; DOL 28: 0.21[0.15-0.28] vs. 0.31 [0.21-0.35], p = 0.015). CONCLUSIONS: In preterm infants, a decline in RIMP after birth was not observed in those with incipient BPD. The pattern of RIMP measured in preterm infants is commensurate with that of pulmonary vascular resistance

Simulated-Physiological Loading Conditions Preserve Biological and Mechanical Properties of Caprine Lumbar Intervertebral Discs in Ex Vivo Culture

Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression

Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described. A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P1B-type ATPase ATP7A underlies MD. To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail. All mutants studied displayed changes in protein expression and intracellular localization parallel to a dramatic decline in their copper-transporting capacity compared to ATP7A the wild-type. We restored these observed defects in ATP7A mutant proteins by culturing the cells at 30°C, which improves the quality of protein folding, similar to that which as has recently has been demonstrated for misfolded ATP7B, a copper transporter homologous to ATP7A. Further, the effect of the canine copper toxicosis protein COMMD1 on ATP7A function was examined as COMMD1 has been shown to regulate the proteolysis of ATP7B proteins. Interestingly, in addition to adjusted growth temperature, binding of COMMD1 partially restored the expression, subcellular localization, and copper-exporting activities of the ATP7A mutants. However, no effect of pharmacological chaperones was observed. Together, the presented data might provide a new direction for developing therapies to improve the residual exporting activity of unstable ATP7A mutant proteins, and suggests a potential role for COMMD1 in this process

Circulating Lipoproteins Are a Crucial Component of Host Defense against Invasive Salmonella typhimurium Infection

Contains fulltext : 79883.pdf (Publisher’s version ) (Open Access)BACKGROUND: Circulating lipoproteins improve the outcome of severe Gram-negative infections through neutralizing lipopolysaccharides (LPS), thus inhibiting the release of proinflammatory cytokines. METHODS/PRINCIPAL FINDINGS: Low density lipoprotein receptor deficient (LDLR-/-) mice, with a 7-fold increase in LDL, are resistant against infection with Salmonella typhimurium (survival 100% vs 5%, p<0.001), and 100 to 1000-fold lower bacterial burden in the organs, compared with LDLR+/+ mice. Protection was not due to differences in cytokine production, phagocytosis, and killing of Salmonella organisms. The differences were caused by the excess of lipoproteins, as hyperlipoproteinemic ApoE-/- mice were also highly resistant to Salmonella infection. Lipoproteins protect against infection by interfering with the binding of Salmonella to host cells, and preventing organ invasion. This leads to an altered biodistribution of the microorganisms during the first hours of infection: after intravenous injection of Salmonella into LDLR+/+ mice, the bacteria invaded the liver and spleen within 30 minutes of infection. In contrast, in LDLR-/- mice, Salmonella remained constrained to the circulation from where they were efficiently cleared, with decreased organ invasion. CONCLUSIONS: plasma lipoproteins are a potent host defense mechanism against invasive Salmonella infection, by blocking adhesion of Salmonella to the host cells and subsequent tissue invasion