Exercise Intensity and Duration Effects on In Vivo Immunity

PURPOSE: To examine the effects of intensity and duration of exercise stress on induction of in vivo immunity in humans using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: Sixty-four healthy males completed either 30 min running at 60% V O2peak (30MI), 30 min running at 80% V O2peak (30HI), 120 min running at 60% V O2peak (120MI), or seated rest (CON). Twenty min later, the subjects received a sensitizing dose of DPCP; and 4 wk later, the strength of immune reactivity was quantified by measuring the cutaneous responses to a low dose-series challenge with DPCP on the upper inner arm. Circulating epinephrine, norepinephrine and cortisol were measured before, after, and 1 h after exercise or CON. Next, to understand better whether the decrease in CHS response on 120MI was due to local inflammatory or T-cell-mediated processes, in a crossover design, 11 healthy males performed 120MI and CON, and cutaneous responses to a dose series of the irritant, croton oil (CO), were assessed on the upper inner arm. RESULTS: Immune induction by DPCP was impaired by 120MI (skinfold thickness -67% vs CON; P < 0.05). However, immune induction was unaffected by 30MI and 30HI despite elevated circulating catecholamines (30HI vs pre: P < 0.01) and greater circulating cortisol post 30HI (vs CON; P < 0.01). There was no effect of 120MI on skin irritant responses to CO. CONCLUSIONS: Prolonged moderate-intensity exercise, but not short-lasting high- or short-lasting moderate-intensity exercise, decreases the induction of in vivo immunity. No effect of prolonged moderate-intensity exercise on the skin's response to irritant challenge points toward a suppression of cell-mediated immunity in the observed decrease in CHS. Diphenylcyclopropenone provides an attractive tool to assess the effect of exercise on in vivo immunity

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales &lt;sup&gt;1-4&lt;/sup&gt; . However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution &lt;sup&gt;5-7&lt;/sup&gt; . Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet ( &lt;sup&gt;13&lt;/sup&gt; C and &lt;sup&gt;15&lt;/sup&gt; N content), mobility ( &lt;sup&gt;87&lt;/sup&gt; Sr/ &lt;sup&gt;86&lt;/sup&gt; Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene &lt;sup&gt;1-5&lt;/sup&gt; . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations

ANGULAR SCATTERING EFFECTS IN ELECTRON CAPTURE BY MULTIPLY CHARGED IONS

Energy-gain measurements have been performed on single-electron capture reactions with low-energy heavy multiply charged ions colliding with He. Because of the large mass ratio between projectile and target, a non-negligible recoil energy is taken up by the target. This results in energy-gain spectra that are shifted and deformed in such a way that they are difficult to resolve into contributions from different reaction channels unless a theoretical analysis including angular scattering effects is performed. We have developed a multichannel model for this purpose which also produces angular differential cross sections. An analysis has been made of the angular scattering present in the collision systems and theoretical energy gain spectra have been used in the assignment of reaction channels. As particular cases we show results from 300 eV O2+ and 200-2000 eV Kr6+ ions capturing one electron from He

Deep inspiration breath-hold radiotherapy for lung cancer: impact on image quality and registration uncertainty in cone beam CT image guidance

OBJECTIVE: We investigated the impact of deep inspiration breath-hold (DIBH) and tumour baseline shifts on image quality and registration uncertainty in image-guided DIBH radiotherapy (RT) for locally advanced lung cancer. METHODS: Patients treated with daily cone beam CT (CBCT)-guided free-breathing (FB) RT had an additional CBCT in DIBH at three fractions. These CBCT scans were offline rigidly registered (on tumour) to FB and DIBH CT scans acquired at planning. All registrations were repeated to evaluate the intraobserver uncertainty. CBCT scans were scored on degree of streak artefacts and visualization of tumour and anatomical structures. We examined the impact of tumour baseline shift between consecutive DIBHs on CBCT image quality. RESULTS: CBCT scans from 15 patients were analysed. Intraobserver image registration uncertainty was approximately 2 mm in both FB and DIBH, except for the craniocaudal direction in FB, where it was >3 mm. On the 31st fraction, the intraobserver uncertainty increased compared with the second fraction. This increase was more pronounced in FB. Image quality scores improved in DIBH compared with FB for all parameters in all patients. Simulated tumour baseline shifts ≤2 mm did not affect the CBCT image quality considerably. CONCLUSION: DIBH CBCT improved image quality and reduced registration uncertainty in the craniocaudal direction in image-guided RT of locally advanced lung cancer. Baseline shifts ≤2 mm in DIBH during CBCT acquisition did not affect image quality. ADVANCES IN KNOWLEDGE: DIBH RT has dosimetric advantages over FB; this work demonstrates an additional benefit of DIBH in terms of registration accuracy because of improved image quality