Effects of 9-hour time zone changes on fatigue and circadian rhythms of sleep/wake and core temperature

Physiological and psychological disruptions caused by transmeridian flights may affect the ability of flight crews to meet operational demands. To study these effects, 9 Royal Norwegian Airforces P3-Orion crewmembers flew from Norway to California (-9 hr), and back (+9 hr). Rectal temperature, heart rate and wrist activity were recorded every 2 min, fatigue and mood were rated every 2 hr during the waking day, and logs were kept of sleep times and ratings. Subjects also completed 4 personality inventories. The time-zone shifts produced negative changes in mood which persisted longer after westward flights. Sleep quality (subjective and objective) and duration were slightly disrupted (more after eastward flights). The circadian rhythms of sleep/wake and temperature both completed the 9-hr delay by day 5 in California, although temperature adjusted more slowly. The size of the delay shift was significantly correlated with scores on extraversion and achievement need personality scales. Response to the 9-hr advance were more variable. One subject exhibited a 15-hr delay in his temperature rhythm, and an atypical sleep/nap pattern. On average, the sleep/wake cycle (but not the temperature rhythm), completed the 9-hr advance by the end of the study. Both rhythms adapted more slowly after the eastward flight

An Economic Analysis of Pecan Orchard Establishment and Management.

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Spongiibacter marinus gen. nov., sp. nov., a halophilic marine bacterium isolated from the boreal sponge Haliclona sp. 1

Strain HAL40bT was isolated from the marine sponge Haliclona sp. 1 collected at the Sula Ridge off the Norwegian coast and characterized by physiological, biochemical and phylogenetic analyses. The isolate was a small rod with a polar flagellum. It was aerobic, Gram-negative and oxidase- and catalase-positive. Optimal growth was observed at 20–30 °C, pH 7–9 and in 3 % NaCl. Substrate utilization tests were positive for arabinose, Tween 40 and Tween 80. Enzyme tests were positive for alkaline phosphatase, esterase lipase (C8), leucine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase and N-acetyl-β-glucosaminidase. The predominant cellular fatty acid was C17 : 1 ω8, followed by C17 : 0 and C18 : 1 ω7. Analysis by matrix-assisted laser desorption/ionization time-of-flight MS was used to characterize the strain, producing a characteristic low-molecular-mass protein pattern that could be used as a fingerprint for identification of members of this species. The DNA G+C content was 69.1 mol%. Phylogenetic analysis supported by 16S rRNA gene sequence comparison classified the strain as a member of the class Gammaproteobacteria. Strain HAL40bT was only distantly related to other marine bacteria including Neptunomonas naphthovorans and Marinobacter daepoensis (type strain sequence similarity >90 %). Based on its phenotypic, physiological and phylogenetic characteristics, it is proposed that the strain should be placed into a new genus as a representative of a novel species, Spongiibacter marinus gen. nov., sp. nov.; the type strain of Spongiibacter marinus is HAL40bT (=DSM 17750T =CCUG 54896T)

Crew factors in flight operations 6: Psychophysiological responses to helicopter operations

Thirty-two helicopter pilots were studied before, during, and after 4-5 day trips providing support services from Aberdeen, Scotland, to rigs in the North Sea oil fields. Early on-duty times obliged subjects to wake up 1.5 hours earlier on trip days than on pretrip days. Consequently, they slept nearly an hour less per night on trips. They reported more fatigue on post-trip days than on pretrip days, suggesting a cumulative effect of duty-related activities and sleep loss. Fatigue and negative affect were higher, and activation lower, by the end of trip days than by the end of pretrip days. The earlier a subject went on duty, the lower his activation by the end of the day. Caffeine consumption increased 42 percent on trip days. The incidence of headache doubled, of back pain increased twelve fold, and of burning eyes quadrupled. In the aircraft studied, thermal discomfort and high vibration levels were common. The longer pilots remained on duty, the more negative their mood became

Crew Factors in Flight Operations 7: Psychophysiological Responses to Overnight Cargo Operations

To document the psychophysiological effects of flying overnight cargo operations, 41 B-727 crew members (average age 38 yr) were monitored before, during, and after one of two typical 8-day trip patterns. During daytime layovers, the average sleep episode was 3 hr (41%) shorter than nighttime sleeps and was rated as lighter, less restorative, and poorer overall. Sleep was frequently split into several episodes and totaled 1.2 hr less per 24 hr than on pretrip days. Each trip pattern included a night off, which was an effective countermeasure against the accumulating sleep debt. The organization of sleep during daytime layovers reflected the interaction of duty timing with circadian physiology. The circadian temperature rhythm did not adapt completely to the inverted wake-rest schedule on duty days, being delayed by about 3 hr. Highest subjective fatigue and lowest activation occurred around the time of the temperature minimum. On duty days, reports of headaches increased by 400%, of congested nose by 200%, and of burning eyes by 900%. Crew members also reported eating more snacks. Compared with daytime short-haul air-transport operations, the overnight cargo trips included fewer duty and flight hours, and had longer layovers. Overnight cargo crews also averaged 5.4 yr younger than their daytime short-haul counterparts. On trips, both groups lost a comparable amount of sleep per 24 hr, but the overnight cargo crews had shorter individual sleep episodes and more broken sleep. These data clearly demonstrate that overnight cargo operations, like other night work, involve physiological disruption not found in comparable daytime operations

BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.

Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones

Metabolic gatekeeper function of B-lymphoid transcription factors.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation

Creating the collective: social media, the Occupy Movement and its constitution as a collective actor

This paper examines the process through which Occupy activists came to constitute themselves as a collective actor and the role of social media in this process. The theoretical framework combines Melucci's (1996) theory of collective identity with insights from the field of organizational communication and particularly from the ‘CCO’ strand – short for ‘Communication is Constitutive of Organizing’. This allows us to conceptualize collective identity as an open-ended and dynamic process that is constructed in conversations and codified in texts. Based on interviews with Occupy activists in New York, London and other cities, I then discuss the communication processes through which the movement was drawing the boundaries with its environment, creating codes and foundational documents, as well as speaking in a collective voice. The findings show that social media tended to blur the boundaries between the inside and the outside of the movement in a way that suited its values of inclusiveness and direct participation. Social media users could also follow remotely the meetings of the general assembly where the foundational documents were ratified, but their voices were not included in the process. The presence of the movement on social media also led to conflicts and negotiations around Occupy's collective voice as constructed on these platforms. Thus, viewing the movement as a phenomenon emerging in communication allows us an insight into the efforts of Occupy activists to create a collective that was both inclusive of the 99% and a distinctive actor with its own identity

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B