Cutaneous exposure to hypoxia does not affect skin perfusion in humans.

$\textbf{Aim:}$ Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O$_2$ availability. Specifically, a reduction in skin-surface PO$_2$ attenuates transcutaneous O$_2$ diffusion, and hence epidermal O$_2$ supply. In response, epidermal HIF-1$\alpha$ expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide-dependent vasodilation. Here, we investigated whether the same mechanism exists in humans. $\textbf{Methods:}$ In a first experiment, eight males rested twice for 8 h in a hypobaric chamber. Once, barometric pressure was reduced by 50%, while systemic oxygenation was preserved by O$_2$-enriched (42%) breathing gas (Hypoxia$_\text{Skin}$), and once barometric pressure and inspired O$_2$ fraction were normal (Control$_1$). In a second experiment, nine males rested for 8 h with both forearms wrapped in plastic bags. O$_2$ was expelled from one bag by nitrogen flushing (Anoxia$_\text{Skin}$), whereas the other bag was flushed with air (Control$_2$). In both experiments, skin blood flux was assessed by laser Doppler on the dorsal forearm, and HIF-1$\alpha$ expression was determined by immunohistochemical staining in forearm skin biopsies. $\textbf{Results:}$ Skin blood flux during Hypoxia$_\text{Skin}$ and Anoxia$_\text{Skin}$ remained similar to the corresponding Control trial ($P$ = 0.67 and $P$ = 0.81). Immunohistochemically stained epidermal HIF-1$\alpha$ was detected on 8.2 ± 6.1 and 5.3 ± 5.7% of the analysed area during Hypoxia$_\text{Skin}$ and Control$_1$ ($P$ = 0.30) and on 2.3 ± 1.8 and 2.4 ± 1.8% during Anoxia$_\text{Skin}$ and Control$_2$ ($P$ = 0.90) respectively. $\textbf{Conclusion:}$ Reductions in skin-surface PO$_2$ do not affect skin perfusion in humans. The unchanged epidermal HIF-1$\alpha$ expression suggests that epidermal O$_2$ homoeostasis was not disturbed by Hypoxia$_\text{Skin}$/Anoxia$_\text{Skin}$, potentially due to compensatory increases in arterial O$_2$ extraction.Gösta Fraenckel Foundatio

Regulation of plasma volume in male lowlanders during 4 days of exposure to hypobaric hypoxia equivalent to 3500 m altitude.

Acclimatization to hypoxia leads to a reduction in plasma volume (PV) that restores arterial O <sub>2</sub> content. Findings from studies investigating the mechanisms underlying this PV contraction have been controversial, possibly as experimental conditions were inadequately controlled. We examined the mechanisms underlying the PV contraction evoked by 4 days of exposure to hypobaric hypoxia (HH) in 11 healthy lowlanders, while strictly controlling water intake, diet, temperature and physical activity. Exposure to HH-induced an ∼10% PV contraction that was accompanied by a reduction in total circulating protein mass, whereas diuretic fluid loss and total body water remained unchanged. Our data support an oncotically driven fluid redistribution from the intra- to the extravascular space, rather than fluid loss, as the mechanism underlying HH-induced PV contraction. Extended hypoxic exposure reduces plasma volume (PV). The mechanisms underlying this effect are controversial, possibly as previous studies have been confounded by inconsistent experimental conditions. Here, we investigated the effect of hypobaric hypoxia (HH) on PV in a cross-over study that strictly controlled for diet, water intake, physical activity and temperature. Eleven males completed two 4-day sojourns in a hypobaric chamber, one in normoxia (NX) and one in HH equivalent to 3500 m altitude. PV, urine output, volume-regulating hormones and plasma protein concentration were determined daily. Total body water (TBW) was determined at the end of both sojourns by deuterium dilution. Although PV was 8.1 ± 5.8% lower in HH than in NX after 24 h and remained ∼10% lower thereafter (all P < 0.002), no differences were detected in TBW (P = 0.17) or in 24 h urine volumes (all P > 0.23). Plasma renin activity and circulating aldosterone were suppressed in HH during the first half of the sojourn (all P < 0.05) but thereafter similar to NX, whereas no differences were detected for copeptin between sojourns (all P > 0.05). Markers for atrial natriuretic peptide were higher in HH than NX after 30 min (P = 0.001) but lower during the last 2 days (P < 0.001). While plasma protein concentration was similar between sojourns, total circulating protein mass (TCP) was reduced in HH at the same time points as PV (all P < 0.03). Despite transient hormonal changes favouring increased diuresis, HH did not enhance urine output. Instead, the maintained TBW and reduced TCP support an oncotically driven fluid redistribution into the extravascular compartment as the mechanism underlying PV contraction

Orientation and symmetries of Alexandrov spaces with applications in positive curvature

We develop two new tools for use in Alexandrov geometry: a theory of ramified orientable double covers and a particularly useful version of the Slice Theorem for actions of compact Lie groups. These tools are applied to the classification of compact, positively curved Alexandrov spaces with maximal symmetry rank.Comment: 34 pages. Simplified proofs throughout and a new proof of the Slice Theorem, correcting omissions in the previous versio

The stable topological-hyperbolic space form problem for complete manifolds of finite volume

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46609/1/222_2005_Article_BF01389189.pd

Age differences in physiological responses to self-paced and incremental V˙O2max\dot V O_{2max} testing

Purpose: A self-paced maximal exercise protocol has demonstrated higher $\dot V O_{2max}$ values when compared against traditional tests. The aim was to compare physiological responses to this self-paced $\dot V O_{2max}$ protocol (SPV) in comparison to a traditional ramp $\dot V O_{2max}$ (RAMP) protocol in young (18–30 years) and old (50–75 years) participants. Methods: Forty-four participants (22 young; 22 old) completed both protocols in a randomised, counter-balanced, crossover design. The SPV included 5 × 2 min stages, participants were able to self-regulate their power output (PO) by using incremental ‘clamps’ in ratings of perceived exertion. The RAMP consisted of either 15 or 20 W min$^{−1}$. Results: Expired gases, cardiac output (Q), stroke volume (SV), muscular deoxyhaemoglobin (deoxyHb) and electromyography (EMG) at the vastus lateralis were recorded throughout. Results demonstrated significantly higher $\dot V O_{2max}$ in the SPV (49.68 ± 10.26 ml kg$^{−1}$ min$^{−1}$) vs. the RAMP (47.70 ± 9.98 ml kg$^{−1}$ min$^{−1}$) in the young, but not in the old group (>0.05). Q and SV were significantly higher in the SPV vs. the RAMP in the young (0.05). No differences seen in deoxyHb and EMG for either age groups (>0.05). Peak PO was significantly higher in the SPV vs. the RAMP in both age groups (<0.05). Conclusion: Findings demonstrate that the SPV produces higher $\dot V O_{2max}$, peak Q and SV values in the young group. However, older participants achieved similar $\dot V O_{2max}$ values in both protocols, mostly likely due to age-related differences in cardiovascular responses to incremental exercise, despite them achieving a higher physiological workload in the SPV

Library of Congress Cataloging in Publication data will

be found on the last printed page of this bookFOREWORD These five essays consolidate several parts of the subject of topological manifolds that were brought within reach by our two short articles [Ki 1] and [KS 1] published in 1969. Many of the theorems proved here were announced by us in [KS 3 1 [KS 4] [SilO]. Certainly we have not labored in isolation; our bibliography bears clear testimony to this! Preliminary versions of segmen ts of these essays (particularly Essay I) have been in limited circulation since early 1970. Polycopied versions of all five were released in August 1972 (from Orsay), and reissued in November 1973. The final camera-ready manuscript was prepared by the second author, Wanda Jones, and Arlene Spurlo~k during 1974 and 1975 using the IBM selectric composer system (hitherto exploited but little by mathematicians, cf. [Whole, p. 435] ). G. Blattmann inked the drawings