A Summary Of: Collecting Sleep, Circadian, Fatigue, and Performance Data in Complex Operational Environments

Sleep loss and circadian misalignment contribute to a meaningful proportion of operational accidents and incidents. Countermeasures and work scheduling designs aimed at mitigating fatigue are typically evaluated in controlled laboratory environments, but the effectiveness of translating such strategies to operational environments can be challenging to assess. This manuscript summarizes an approach for collecting sleep, circadian, fatigue, and performance data in a complex operational environment. We studied 44 airline pilots over 34 days while they flew a fixed schedule, which included a baseline data collection with 5 days of mid-morning flights, four early flights, four high-workload mid-day flights, and four late flights that landed after midnight. Each work block was separated by 3-4 days of rest. To assess sleep, participants wore a wrist-worn research-validated activity monitor continuously and completed daily sleep diaries. To assess the circadian phase, pilots were asked to collect all urine produced in four or eight hourly bins during the 24 h after each duty block for the assessment of 6-sulfatoxymelatonin (aMT6s), which is a biomarker of the circadian rhythm. To assess subjective fatigue and objective performance, participants were provided with a touchscreen device used to complete the Samn-Perelli Fatigue Scale and Psychomotor Vigilance Task (PVT) during and after each flight, and at wake-time, mid-day, and bedtime. Using these methods, it was found that sleep duration was reduced during early starts and late finishes relative to baseline. Circadian phase shifted according to duty schedule, but there was a wide range in the aMT6s peak between individuals on each schedule. PVT performance was worse on the early, high-workload, and late schedules relative to baseline. Overall, the combination of these methods was practical and effective for assessing the influence of sleep loss and circadian phase on fatigue and performance in a complex operational environment

Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis

We developed a microfluidics-based model to quantify cell-level processes modulating the pathophysiology of sickle cell disease (SCD). This in vitro model enabled quantitative investigations of the kinetics of cell sickling, unsickling, and cell rheology. We created short-term and long-term hypoxic conditions to simulate normal and retarded transit scenarios in microvasculature. Using blood samples from 25 SCD patients with sickle hemoglobin (HbS) levels varying from 64 to 90.1%, we investigated how cell biophysical alterations during blood flow correlated with hematological parameters, HbS level, and hydroxyurea (HU) therapy. From these measurements, we identified two severe cases of SCD that were also independently validated as severe from a genotype-based disease severity classification. These results point to the potential of this method as a diagnostic indicator of disease severity. In addition, we investigated the role of cell density in the kinetics of cell sickling. We observed an effect of HU therapy mainly in relatively dense cell populations, and that the sickled fraction increased with cell density. These results lend support to the possibility that the microfluidic platform developed here offers a unique and quantitative approach to assess the kinetic, rheological, and hematological factors involved in vasoocclusive events associated with SCD and to develop alternative diagnostic tools for disease severity to supplement other methods. Such insights may also lead to a better understanding of the pathogenic basis and mechanism of drug response in SCD.National Institutes of Health (U.S.) (R01HL094270)National Institutes of Health (U.S.) (U01HL114476

Prominent Role Of Platelets In The Formation Of Circulating Neutrophil-red Cell Heterocellular Aggregates In Sickle Cell Anemia.

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Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia

The hydroxycarbamide (HC)-inducible small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR) protein has recently been shown to play a pivotal role in HBG induction and erythroid maturation by causing cell apoptosis and G1/S-phase arrest. Our preliminary analysis indicated that HC inducibility is transcriptionally regulated by elements within the SAR1A promoter. This study aimed to assess whether polymorphisms in the SAR1A promoter are associated with differences Hb F levels or HC therapeutic responses among sickle cell disease (SCD) patients. We studied 386 individuals with SCD comprised of 269 adults treated with or without HC and 117 newborns with SCD identified from a newborn screening program. Three previously unknown single nucleotide polymorphisms (SNPs) in the upstream 5′UTR (−809 C>T, −502 G>T and −385 C>A) were significantly associated with the fetal haemoglobin (HbF) response in Hb SS patients treated with HC (P < 0·05). In addition, four SNPs (rs2310991, −809 C>T, −385 C>A and rs4282891) were significantly associated with the change in absolute HbF after 2 years of treatment with HC. These data suggest that variation within SAR1A regulatory elements might contribute to inter-individual differences in regulation of HbF expression and patient responses to HC in SCD

Order from disorder in lattice QCD at high density

We investigate the properties of the ground state of strong coupling lattice QCD at finite density. Our starting point is the effective Hamiltonian for color singlet objects, which looks at lowest order as an antiferromagnet, and describes meson physics with a fixed baryon number background. We concentrate on uniform baryon number backgrounds (with the same baryon number on all sites), for which the ground state was extracted in an earlier work, and calculate the dispersion relations of the excitations. Two types of Goldstone boson emerge. The first, antiferromagnetic spin waves, obey a linear dispersion relation. The others, ferromagnetic magnons, have energies that are quadratic in their momentum. These energies emerge only when fluctuations around the large-N_c ground state are taken into account, along the lines of ``order from disorder'' in frustrated magnetic systems. Unlike other spectrum calculations in order from disorder, we employ the Euclidean path integral. For comparison, we also present a Hamiltonian calculation using a generalized Holstein-Primakoff transformation. The latter can only be constructed for a subset of the cases we consider.Comment: 24 pages, 6 figures, 1 tabl

Global 3D Simulations of Disc Accretion onto the classical T Tauri Star BP Tauri

The magnetic field of the classical T Tauri star BP Tau can be approximated as a superposition of dipole and octupole moments with respective strengths of the polar magnetic fields of 1.2 kG and 1.6 kG (Donati et al. 2008). We adopt the measured properties of BP Tau and model the disc accretion onto the star. We observed in simulations that the disc is disrupted by the dipole component and matter flows towards the star in two funnel streams which form two accretion spots below the dipole magnetic poles. The octupolar component becomes dynamically important very close to the star and it redirects the matter flow to higher latitudes. The spots are meridionally elongated and are located at higher latitudes, compared with the pure dipole case, where crescent-shaped, latitudinally elongated spots form at lower latitudes. The position and shape of the spots are in good agreement with observations. The disk-magnetosphere interaction leads to the inflation of the field lines and to the formation of magnetic towers above and below the disk. The magnetic field of BP Tau is close to the potential only near the star, inside the magnetospheric surface, where magnetic stress dominates over the matter stress. A series of simulation runs were performed for different accretion rates. They show that an accretion rate is lower than obtained in many observations, unless the disc is truncated close to the star. The torque acting on the star is about an order of magnitude lower than that which is required for the rotational equilibrium. We suggest that a star could lose most of its angular momentum at earlier stages of its evolution.Comment: 11 pages, 13 figures, submitted to MNRA

The XMM-Newton survey of the Small Magellanic Cloud: XMMUJ005011.2-730026 = SXP214, a Be/X-ray binary pulsar

In the course of the XMM-Newton survey of the Small Magellanic Cloud (SMC), a region to the east of the emission nebula N19 was observed in November 2009. To search for new candidates for high mass X-ray binaries the EPIC PN and MOS data of the detected point sources were investigated and their spectral and temporal characteristics identified. A new transient (XMMUJ005011.2-730026= SXP214) with a pulse period of 214.05 s was discovered; the source had a hard X-ray spectrum with power-law index of ~0.65. The accurate X-ray source location permits the identification of the X-ray source with a ~15th magnitude Be star, thereby confirming this system as a new Be/X-ray binary.Comment: 8 pages 11 figures. Accepted for publication in MNRA

Global 3D Simulations of Disc Accretion onto the classical T Tauri Star V2129 Oph

The magnetic field of the classical T Tauri star V2129 Oph can be modeled approximately by superposing slightly tilted dipole and octupole moments, with polar magnetic field strengths of 0.35kG and 1.2kG respectively (Donati et al. 2007). Here we construct a numerical model of V2129 Oph incorporating this result and simulate accretion onto the star. Simulations show that the disk is truncated by the dipole component and matter flows towards the star in two funnel streams. Closer to the star, the flow is redirected by the octupolar component, with some of the matter flowing towards the high-latitude poles, and the rest into the octupolar belts. The shape and position of the spots differ from those in a pure dipole case, where crescent-shaped spots are observed at the intermediate latitudes. Simulations show that if the disk is truncated at the distance of 6.2 R_* which is comparable with the co-rotation radius, 6.8 R_*, then the high-latitude polar spots dominate, but the accretion rate obtained from the simulations is about an order of magnitude lower than the observed one. The accretion rate matches the observed one if the disk is disrupted much closer to the star, at 3.4 R_*. However, the octupolar belt spots strongly dominate. Better match has been obtained in experiments with a dipole field twice as strong. The torque on the star from the disk-magnetosphere interaction is small, and the time-scale of spin evolution, 2 x10^7-10^9 years is longer than the 2x10^6 years age of V2129 Oph. The external magnetic flux of the star is strongly influenced by the disk: the field lines connecting the disk and the star inflate and form magnetic towers above and below the disk. The potential (vacuum) approximation is still valid inside the Alfv\'en (magnetospheric) surface where the magnetic stress dominates over the matter stress.Comment: 15 pages, 15 figures, after major revision, added 3 figures, 2 tables. Accepted to MNRA

RV dysfunction by MRI is associated with elevated transpulmonary gradient and poor prognosis in patients with sickle cell associated pulmonary hypertension

Patients with sickle cell disease (SCD) and pulmonary hypertension (PH) have increased mortality. SCD-PH is often complicated by high cardiac output (CO) related to anemia. The transpulmonary gradient (TPG) reflects a pressure differential across the pulmonary vascular bed without the confounding effect of CO (PVR=TPG/CO). Based on the cardiac transplant literature, a TPG ≥ 12 mmHg indicates significant pulmonary arterial hypertension (PAH). With PH, there is often morphologic adaptation by the right ventricle (RV). In idiopathic PAH, RV dilation and decreased function have been correlated with poor prognosis. We hypothesize that patients with SCD and a TPG ≥ 12 mmHg would have lower functional capacity, increased mortality, and evidence of RV dysfunction on cardiac MRI (CMR)