Biogeography of time partitioning in mammals

Many animals regulate their activity over a 24-h sleep–wake cycle, concentrating their peak periods of activity to coincide with the hours of daylight, darkness, or twilight, or using different periods of light and darkness in more complex ways. These behavioral differences, which are in themselves functional traits, are associated with suites of physiological and morphological adaptations with implications for the ecological roles of species. The biogeography of diel time partitioning is, however, poorly understood. Here, we document basic biogeographic patterns of time partitioning by mammals and ecologically relevant large-scale patterns of natural variation in “illuminated activity time” constrained by temperature, and we determine how well the first of these are predicted by the second. Although the majority of mammals are nocturnal, the distributions of diurnal and crepuscular species richness are strongly associated with the availability of biologically useful daylight and twilight, respectively. Cathemerality is associated with relatively long hours of daylight and twilight in the northern Holarctic region, whereas the proportion of nocturnal species is highest in arid regions and lowest at extreme high altitudes. Although thermal constraints on activity have been identified as key to the distributions of organisms, constraints due to functional adaptation to the light environment are less well studied. Global patterns in diversity are constrained by the availability of the temporal niche; disruption of these constraints by the spread of artificial lighting and anthropogenic climate change, and the potential effects on time partitioning, are likely to be critical influences on species’ future distributions.Natural cycles of light and darkness structure the environment of the majority of eukaryotic organisms. The rotation of the Earth partitions time into regular cycles of day and night, and although all points on the Earth’s surface receive roughly equal durations of light and darkness over the course of a year, at mid to high latitudes seasonal variation in day length imposes an uneven distribution throughout the annual cycle. During the hours when the sun is below the horizon, there is seasonal and latitudinal variation in the duration of “biologically useful semidarkness” in the form of twilight and moonlight (1), modified by both the lunar cycle and variable cloud cover, providing changing opportunities for animals able to use visual cues for key behaviors including foraging, predator avoidance, and reproduction (2–6). Activity during both daylight and semidarkness may be further constrained by covariance between the natural cycles of light and temperature; the metabolic costs of thermoregulation place constraints on the time available for activity (7). Thermal constraints may limit nocturnal activity when nighttime temperatures are low, and diurnal activity when temperatures are high. Furthermore, energetic constraints may force some species to be active throughout hours of both light and darkness (8). Where energetic and thermal costs are not prohibitive, temporal niche partitioning may occur as species specialize and avoid competition by concentrating their activity within a particular section along the light gradient (9, 10). Behavioral traits are associated with a range of specialized adaptations, particularly in visual systems and eye morphology (11) and energetics and resource use (6, 12). Thus, some species are apparently obligately diurnal in their peak activity patterns, some obligately nocturnal, obligately crepuscular (active primarily during twilight), or obligately cathemeral (significant activity both during daylight and night), and others make facultative use of both daylight and night (13), or show seasonal and/or geographical variation in their strategy. Strict nocturnality and diurnality are hence two ends of a continuum of possible strategies for partitioning time over the 24-h cycle. As properties of organisms that strongly influence performance within a particular environment, these strategies can be considered functional traits in themselves (14), but are also associated with suites of adaptations, with implications for the ecological roles of species and individuals. Crepuscular and cathemeral species may have intermediate adaptations (15), and behavior may be flexible to vary within species and among individuals according to factors such as time of year, habitat structure, food availability, age, temperature, and the presence or absence of predators (16–18).The ecology of diel time partitioning by organisms remains rather poorly understood (19, 20). Studies have considered the adaptive mechanisms behind strategies within a single ecosystem, including predator avoidance, energetic constraints, diet quality, and interspecific competition (9, 21). Meanwhile, although mapping functional traits has become a core technique in functional biogeography (22, 23), surprisingly little is known about the biogeography of diel activity patterns, and the extent to which they are determined by geographic gradients in light and climate. Addressing such issues has become more pressing with growth in the evidence for a wide range of ecological impacts of both anthropogenic climatic change and nighttime light pollution (24–28). Natural cycles of light have remained consistent for extremely long geological periods, providing a rather invariant context, and a very reliable set of potential environmental cues. The continued spread of electric lighting has caused substantial disruption to how these cycles are experienced by many organisms, exerting a novel environmental pressure (29). Direct illumination of the environment has quite localized effects, but sky glow—the amplified night sky brightness that is produced by upwardly emitted and reflected electric light being scattered by water, dust, and gas molecules in the atmosphere—can alter light regimes over extensive areas. Indeed, under cloudy conditions in urban areas, sky glow has been shown to be of an equivalent or greater magnitude than high-elevation summer moonlight (30). Understanding the biogeography of time partitioning by organisms provides a first step toward determining where such changes are likely to have the greatest impact.In this paper, we (i) document basic biogeographic patterns of time partitioning by organisms, using terrestrial mammals as a case study; (ii) document ecologically relevant large-scale patterns of natural variation in “biologically useful” natural light, constrained by temperature; and (iii) determine how well the first of these are predicted by the second. Mammals provide an interesting study group, being globally distributed, occupying a broad range of environments, and exhibiting a wide diversity of time-partitioning behavior. Much concern has also been expressed as to the potential impacts of nighttime light pollution on the group, and there are many studies documenting significant influences (31, 32). Due to the global nature of this study, and the paucity of detailed information on time partitioning reported for many species, our focus is on a high-level categorization, allocating species to one of four temporal niches: nocturnal, diurnal, cathemeral, and crepuscular (Fig. 1), albeit with the acknowledgment that in many species behavior occurs along a continuum of possible strategies that may be more flexible and complex.Open in a separate windowFig. 1.Examples of recorded diel activity patterns illustrating the four main time-partitioning strategies used to classify terrestrial mammals in this study (64–67).     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Atrial fibrosis quantified using late gadolinium enhancement MRI is associated with sinus node dysfunction requiring pacemaker implant

Atrial Fibrosis and Sinus Node Dysfunction . Introduction: Sinus node dysfunction (SND) commonly manifests with atrial arrhythmias alternating with sinus pauses and sinus bradycardia. The underlying process is thought to be because of atrial fibrosis. We assessed the value of atrial fibrosis, quantified using Late Gadolinium Enhanced‐MRI (LGE‐MRI), in predicting significant SND requiring pacemaker implant. Methods: Three hundred forty‐four patients with atrial fibrillation (AF) presenting for catheter ablation underwent LGE‐MRI. Left atrial (LA) fibrosis was quantified in all patients and right atrial (RA) fibrosis in 134 patients. All patients underwent catheter ablation with pulmonary vein isolation with posterior wall and septal debulking. Patients were followed prospectively for 329 ± 245 days. Ambulatory monitoring was instituted every 3 months. Symptomatic pauses and bradycardia were treated with pacemaker implantation per published guidelines. Results: The average patient age was 65 ± 12 years. The average wall fibrosis was 16.7 ± 11.1% in the LA, and 5.3 ± 6.4% in the RA. RA fibrosis was correlated with LA fibrosis (R²= 0.26; P < 0.01). Patients were divided into 4 stages of LA fibrosis (Utah I: <5%, Utah II: 5–20%, Utah III: 20–35%, Utah IV: >35%). Twenty‐two patients (mean atrial fibrosis, 23.9%) required pacemaker implantation during follow‐up. Univariate and multivariate analysis identified LA fibrosis stage (OR, 2.2) as a significant predictor for pacemaker implantation with an area under the curve of 0.704. Conclusions: In patients with AF presenting for catheter ablation, LGE‐MRI quantification of atrial fibrosis demonstrates preferential LA involvement. Significant atrial fibrosis is associated with clinically significant SND requiring pacemaker implantation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 44‐50, January 2012)     

Do modern total knee replacements offer better value for money? A health economic analysis

Purpose

Cost effectiveness is an increasingly important factor in today’s healthcare environment, and selection of arthroplasty implant is not exempt from such concerns. Quality adjusted life years (QALYs) are the typical tool for this type of evaluation. Using this methodology, joint arthroplasty has been shown to be cost effective; however, studies directly comparing differing prostheses are lacking.

Methods

Data was gathered in a single-centre prospective double-blind randomised controlled trial comparing the outcome of modern and traditional knee implants, using the Short Form 6 dimensional (SF-6D) score and quality adjusted life year (QALY) methodology.

Results

There was significant improvement in the SF-6D score for both groups at one year (p?<?0.0001). The calculated overall life expectancy for the study cohort was 15.1 years, resulting in an overall QALY gain of 2.144 (95 % CI 1.752–2.507). The modern implant group demonstrated a small improvement in SF-6D score compared to the traditional design at one year (0.141 versus 0.143, p?=?0.94). This difference resulted in the modern implant costing £298 less per QALY at one year.

Conclusion

This study demonstrates that modern implant technology does not influence the cost-effectiveness of TKA using the SF-6D and QALY methodology. This type of analysis however assesses health status, and is not sensitive to joint specific function. Evolutionary design changes in implant technology are thus unlikely to influence QALY analysis following joint replacement, which has important implications for implant procurement.     

Growth guidance of angular lower limb deformities using a one-third two-hole tubular plate

Purpose

The eight-plate system for angular deformity correction is well known, reliable and effective at any age during growth. Due to high implant costs, we sought to evaluate the effectiveness and safety of a less expensive alternative.

Methods

Between 2006 and 2011, 41 children with angular deformities were managed using a two-hole one-third tubular plate in cases where an eight plate would normally be indicated. Inclusion criteria in this retrospective study were: genu valgum and genu varum. X-ray documentation was performed before and after surgery and patients were followed clinically every 3 months after surgery. The cost per implant was 361.40 Sfr (Swiss Francs) compared to the eight plate at 737 Sfr.

Results

Mean time for correction was 13 months. A mean LDFA/MPTA after correction of 89.9°/86.8° was recorded, as well as a mean correction angle of 6.8°/6.6°. The complication rate was 6.6 % (one superficial wound infection and one insufficient correction in an older child). These results compare favourably with published data on the eight plate.

Conclusion

The two hole one-third tubular plate seems to be a clinically and also cost effective alternative to the eight plate. Full deformity correction is gained for a fraction of the cost. Level of Evidence: Level III     

Subacute haematotoxicity after PRRT with <Superscript>177</Superscript>Lu-DOTA-octreotate: prognostic factors,incidence and course

Purpose

In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from ¹³¹I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate (¹⁷⁷Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit.

Methods

The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined.

Results

Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0?×?10⁹/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67?±?7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq ¹⁷⁷Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients.

Conclusion

The incidence of subacute haematological toxicity after PRRT with ¹⁷⁷Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from ¹³¹I, seems not to be valid for PRRT with ¹⁷⁷Lu-DOTATATE.