Dopaminergic treatment strategies for people with Parkinson's disease in Europe: a retrospective analysis of PRISM trial data.

BACKGROUND: Levodopa (LD) is the most effective drug to treat Parkinson's disease (PD). The recently concluded multinational Parkinson's Real-World Impact Assessment (PRISM) trial revealed highly variable prescription patterns of LD monotherapy across six European countries. The reasons remain unclear. METHODS: In this post hoc analysis of PRISM trial data, we used multivariate logistic regression analysis to identify socio-economic factors affecting prescription practice. We applied receiver-operated characteristics and split sample validation to test model accuracy to predict treatment class (LD monotherapy vs. all other treatments). RESULTS: Subject age, disease duration, and country of residence were significant predictors of treatment class. The chance of receiving LD monotherapy increased by 6.9% per year of age. In contrast, longer disease duration reduced the likelihood of receiving LD monotherapy by 9.7% per year. Compared to the other countries, PD patients in Germany were 67.1% less likely and their counterparts in the UK 86.8% more likely to receive an LD monotherapy. The model classification accuracy of treatment class assignment was 80.1%. The area under the curve to predict treatment condition was 0.758 (95% CI [0.715, 0.802]). Split sample validation revealed poor sensitivity (36.6%), but excellent specificity (92.7%) to predict treatment class. CONCLUSION: The relative lack of socio-economic variables affecting prescription practice in the study sample and limited model accuracy to predict treatment class suggest the presence of additional, country-specific factors affecting prescription patterns that were not assessed in the PRISM trial. Our findings indicate that physicians still avoid prescribing LD monotherapy to younger PD patients.

How context affects transdisciplinary research: insights from Asia, Africa and Latin America.

Transdisciplinary research (TDR) has been developed to generate knowledge that effectively fosters the capabilities of various societal actors to realize sustainability transformations. The development of TDR theories, principles, and methods has been largely governed by researchers from the global North and has reflected their contextual conditions. To enable more context-sensitive TDR framing, we sought to identify which contextual characteristics affect the design and implementation of TDR in six case studies in Asia, Latin America, and Africa, and what this means for TDR as a scientific approach. To this end, we distinguished four TDR process elements and identified several associated context dimensions that appeared to influence them. Our analysis showed that contextual characteristics prevalent in many Southern research sites-such as highly volatile socio-political situations and relatively weak support infrastructure-can make TDR a challenging endeavour. However, we also observed a high degree of variation in the contextual characteristics of our sites in the global South, including regarding group deliberation, research freedom, and dominant perceptions of the appropriate relationship between science, society, and policy. We argue that TDR in these contexts requires pragmatic adaptations as well as more fundamental reflection on underlying epistemological concepts around what it means to conduct "good science", as certain contextual characteristics may influence core epistemological values of TDR. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01201-3.

Evaluation of long-term functional donor-site morbidity after deep circumflex iliac crest artery bone flap harvest.

PURPOSE: Free flap surgery can be associated with donor-site morbidity. The purpose of this study was to analyze long-term functional outcomes at the donor site after deep circumflex iliac artery (DCIA) bone flap harvesting. METHODS: Fourteen patients (8 men and 6 women, mean age 53.9 years; range 22-87 years) with mandible resection (8 carcinomas, 4 ameloblastomas, 1 osteonecrosis, and 1 myxofibroma) and DCIA flap reconstruction were included in an observational study. Ranges of motion in the hip and lumbar spine, Harris hip score (HHS), jumping mechanography, chair rising, and balance testing were performed on a ground force reaction plate (Leonardo Mechanograph, Novotec Medical GmbH, Germany). The primary outcome was the Esslinger fitness index (EFI, maximum peak power in W/kg normalized to age and gender). RESULTS: Functional assessment was performed preoperatively and 29.0 months postoperatively (range 12-51 months). Mean DCIA flap length was 6.3 cm (range 3.3-10.1 cm). Jaw reconstruction was successful in all cases. HHS (99.2 vs. 97.7 points, P = .004) and all ranges of motion in the lumbar spine and hip joint except for dorsal extension were significantly reduced postoperatively (range -4° to -11.0°). There was no significant difference between pre- and postoperative EFI (77.9% vs. 74.28%, P = .591) and body sway (1.25 cm2 vs. 2.01 cm2 , P = .806). Sensory deficits (n = 5), load dependent pain (n = 3), and limitations of daily activities (n = 3) were subjective complaints. CONCLUSION: Functional donor site morbidity after DCIA harvesting can be expected to be low in the long-term.

Functional donor site morbidity longer than one year after fibula free flap: A prospective biomechanical analysis.

OBJECTIVES: The fibula free flap is the workhorse procedure for osseous reconstruction. The objective of this study was to investigate long-term functional outcomes of the harvesting site. PATIENTS AND METHODS: About 19 patients (10 male, 9 female, mean age 58.1 years) were available for the long-term analysis 13-51 months after surgery. Jumping mechanography and balance testing on a ground force reaction plate (Leonardo Mechanograph GFRP) were performed before and surgery. The Esslinger Fitness Index (EFI, maximum peak power in W/kg normalized for age and gender) was considered as primary endpoint. Secondary outcomes were maximum force, range of motion in the ankle joint, sensory limitations, the American Orthopedic Foot and Ankle Society Score (AOFAS-Score), and subjective perceptions. RESULTS: We found no significant difference between pre- and postoperative EFI (70.4% versus 66.0%, P = 0.07) and body sway (1.72 cm2 versus 2.60 cm2 , P = 0.093). The AOFAS-Score was reduced by 8.8 points (99.1 points versus 90.3 points, P < 0.001). Dorsal extenstion (31.6° versus 24.1°, P < 0.001) and flexion (32.3 versus 25.6° flexion, P = 0.011) were significantly reduced and 6 patients had chronic pain. CONCLUSIONS: Reduced peak power and balance ability seem to be reversible short-term effects after fibula harvesting. We recommend preoperative patient education and standardized protocols for physiotherapy.

The Adaptation for Conservation Targets (ACT) framework: a tool for incorporating climate change into natural resource management.

As natural resource management agencies and conservation organizations seek guidance on responding to climate change, myriad potential actions and strategies have been proposed for increasing the long-term viability of some attributes of natural systems. Managers need practical tools for selecting among these actions and strategies to develop a tailored management approach for specific targets at a given location. We developed and present one such tool, the participatory Adaptation for Conservation Targets (ACT) framework, which considers the effects of climate change in the development of management actions for particular species, ecosystems and ecological functions. Our framework is based on the premise that effective adaptation of management to climate change can rely on local knowledge of an ecosystem and does not necessarily require detailed projections of climate change or its effects. We illustrate the ACT framework by applying it to an ecological function in the Greater Yellowstone Ecosystem (Montana, Wyoming, and Idaho, USA)--water flows in the upper Yellowstone River. We suggest that the ACT framework is a practical tool for initiating adaptation planning, and for generating and communicating specific management interventions given an increasingly altered, yet uncertain, climate.

Designing climate-smart conservation: guidance and case studies.

To be successful, conservation practitioners and resource managers must fully integrate the effects of climate change into all planning projects. Some conservation practitioners are beginning to develop, test, and implement new approaches that are designed to deal with climate change. We devised four basic tenets that are essential in climate-change adaptation for conservation: protect adequate and appropriate space, reduce nonclimate stresses, use adaptive management to implement and test climate-change adaptation strategies, and work to reduce the rate and extent of climate change to reduce overall risk. To illustrate how this approach applies in the real world, we explored case studies of coral reefs in the Florida Keys; mangrove forests in Fiji, Tanzania, and Cameroon; sea-level rise and sea turtles in the Caribbean; tigers in the Sundarbans of India; and national planning in Madagascar. Through implementation of these tenets conservation efforts in each of these regions can be made more robust in the face of climate change. Although these approaches require reconsidering some traditional approaches to conservation, this new paradigm is technologically, economically, and intellectually feasible.

Global warming and extinctions of endemic species from biodiversity hotspots.

Global warming is a key threat to biodiversity, but few researchers have assessed the magnitude of this threat at the global scale. We used major vegetation types (biomes) as proxies for natural habitats and, based on projected future biome distributions under doubled-CO2 climates, calculated changes in habitat areas and associated extinctions of endemic plant and vertebrate species in biodiversity hotspots. Because of numerous uncertainties in this approach, we undertook a sensitivity analysis of multiple factors that included (1) two global vegetation models, (2) different numbers of biome classes in our biome classification schemes, (3) different assumptions about whether species distributions were biome specific or not, and (4) different migration capabilities. Extinctions were calculated using both species-area and endemic-area relationships. In addition, average required migration rates were calculated for each hotspot assuming a doubled-CO2 climate in 100 years. Projected percent extinctions ranged from <1 to 43% of the endemic biota (average 11.6%), with biome specificity having the greatest influence on the estimates, followed by the global vegetation model and then by migration and biome classification assumptions. Bootstrap comparisons indicated that effects on hotpots as a group were not significantly different from effects on random same-biome collections of grid cells with respect to biome change or migration rates; in some scenarios, however, botspots exhibited relatively high biome change and low migration rates. Especially vulnerable hotspots were the Cape Floristic Region, Caribbean, Indo-Burma, Mediterranean Basin, Southwest Australia, and Tropical Andes, where plant extinctions per hotspot sometimes exceeded 2000 species. Under the assumption that projected habitat changes were attained in 100 years, estimated global-warming-induced rates of species extinctions in tropical hotspots in some cases exceeded those due to deforestation, supporting suggestions that global warming is one of the most serious threats to the planet's biodiversity.

Solar UV radiation enhances the toxicity of arsenic in Ceriodaphnia dubia.

Extensive research exists regarding the toxicity of metals (including arsenic) to aquatic invertebrates. However, there has been little consideration of potential synergies between metals and ultraviolet (UV) radiation--despite considerable debate on this topic in human health research. Ultraviolet radiation is nearly ubiquitous in the natural environment, but it is generally overlooked as a confounding variable in toxicological assessments. We evaluate synergies between arsenic and solar UV radiation using the crustacean, Ceriodaphnia dubia. Both laboratory (with simulated solar radiation) and outdoor (with natural solar radiation) factorial experiments were performed with two intensities of UV (low and high) and four arsenic concentrations (0, 1, 1.25 and 1.5 mg/l). The laboratory experiment was multigenerational, examining survival and fecundity effects. The combination of high UV + 1.5 mg/l As adversely impacted survival; whereas, High UV + 0 mg/l As and Low UV + 1.5 mg/l As treatments did not. These results suggest synergism. This pattern was consistent for all three generations. Fecundity effects were not consistent across generations, and arsenic was demonstrated to have a greater impact than UV. Outdoor experiments were limited to assessing survival. Exposures in September 1999 resulted in a pattern similar to that in the laboratory exposure. High UV + 1.5 mg/l As treatment elicited diminished survival as compared to high UV + 0 mg/l As and low UV + 1.5 mg/l As. These results indicate that a synergistic effect between arsenic and UV exposure is possible under ambient conditions and within a relatively narrow dose range. The mechanism of this effect is unknown but could include synergistic genotoxic or oxidative stress. These findings point to the importance of using realistic UV exposures when determining criteria for protection of aquatic life.

The role of the egg jelly coat in protecting Hyla regilla and Bufo canorus embryos from ultraviolet B radiation during development.

BACKGROUND: Previous studies have suggested that Ultraviolet B (UVB) radiation may play a role in amphibian population declines. Some of these studies also indicate that egg hatching success is unaltered in some species of anurans as a result of UVB exposure. It has been proposed that the egg mass jelly provides photoprotection to the developing embryos. METHODS: Direct spectrophotometric scans of egg jelly, scans of egg jelly methanol extracts, and experimental manipulation in a solar simulator during development were all used to assess the role of egg mass jelly as a photoprotective agent. RESULTS/DISCUSSION: For Hyla regilla, scans of egg jelly and methanolic extracts (for mycosporine-like amino acid content) both displayed no absorption in the UV range. Experimental manipulation (removal of egg mass jelly) with both Hyla regilla and Bufo canorus egg masses in a solar simulator demonstrated that egg mass jelly played no apparent role in photoprotection of either of these species. CONCLUSIONS: Based on the results in this study it seems unlikely that the egg jelly coat is playing a crucial role in protecting developing embryos from the impact of UVB radiation.