Radiometals possess an exceptional breadth of decay properties and have been applied to medicine with great success for several decades. The majority of current clinical use involves diagnostic ...procedures, which use either positron-emission tomography (PET) or single-photon imaging to detect anatomic abnormalities that are difficult to visualize using conventional imaging techniques (e.g., MRI and X-ray). The potential of therapeutic radiometals has more recently been realized and relies on ionizing radiation to induce irreversible DNA damage, resulting in cell death. In both cases, radiopharmaceutical development has been largely geared toward the field of oncology; thus, selective tumor targeting is often essential for efficacious drug use. To this end, the rational design of four-component radiopharmaceuticals has become popularized. This Review introduces fundamental concepts of drug design and applications, with particular emphasis on bifunctional chelators (BFCs), which ensure secure consolidation of the radiometal and targeting vector and are integral for optimal drug performance. Also presented are detailed accounts of production, chelation chemistry, and biological use of selected main group and rare earth radiometals.
We build a general equilibrium dynamic model in which individual investors are endowed with “warm-glow” preferences à la Andreoni (1990) so that they feel partly responsible for the pollution content ...of their portfolio. Through investors’ portfolio choice, firms are induced to engage in costly abatement activities, given that higher pollution also implies a higher cost of capital. In this scenario, we characterize the equilibrium of the economy and investigate, through a fiscal reform analysis, the effects of such tax instruments on the equilibrium scale of the economy, per-capita consumption, pollution abatement and “pollution premium”. We show that an increase of the pollution tax, while reducing pollution, also depresses consumption, the scale of the economy and the pollution premium. On the contrary, an increase of subsidies on abatement activity increases the scale of the economy and can also decrease pollution and the pollution premium and increase per-capita consumption. All our results have relevant testable implications, which we leave for future empirical research.
•We build a general equilibrium dynamic model with socially responsible investors.•Firms engage in abatement activities because pollution implies higher capital costs.•We compare the effects of taxes on pollution and subsidies on firms' abatement.•The pollution tax reduces pollution, consumption, capital and the pollution premium.•Subsidies increase capital, can decrease pollution (premium), can boost consumption.
Osteochondral lesions of the ankle are common, but only a small proportion of these lesions are found on the tibial plafond (osteochondral lesions of the tibial plafond, ie, OLTP). By and large, ...surgical treatment strategies for OLTP have been derived from techniques employed for those of the talus (ie, osteochondral lesion of the talus). Despite the clinical success of surgical treatments for osteochondral lesion of the talus, namely bone marrow stimulation, it is quite possible that OLTP may not respond similarly, given the unique anatomy and biomechanical properties of the tibia. To this end, the literature surrounding OLTP is relatively sparse, and studies evaluating the clinical and radiographic outcomes of treatments specific to OLTP are necessary. Still, if it works for the talus, it seems sensible that it could work for the plafond. Pending future research, there is no need to reinvent the wheel.
Evidence-based medicine is the commanding philosophy of patient care in the field of orthopaedic surgery, and analysis of clinical research is facilitated by instruments and scales developed for ...assessing methodologic quality and validity of conclusions. In contrast, little consideration has been given to developing metrics to assess the quality and validity of orthopaedic ex vivo and laboratory research. This is easier said than done because these studies may be heterogeneous and complex in design, and methodologic details may not be intuitive to (non-engineer) readers. The recently described Biomechanics Objective Basic Science Quality Assessment Tool (BOBQAT) represents a reliable means to assess cadaveric biomechanical studies. The BOBQAT emphasizes essential study elements including a clinically relevant, answerable purpose; detailed description of the specimens studied; thorough description of surgical technique; and careful consideration of loading conditions including clinically relevant cyclic loading. The BOBQAT provides a logical recipe for the design of future studies, a mechanism of quality assessment for systematic reviews, and a framework for readers to assess biomechanical research consistent with the ethos of evidence-based medicine.
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the ...observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
This study aimed to determine the effect of plyometric training (PT) when added to habitual gymnastic training (HT) on handspring vault (HV) performance variables. Twenty youth female competitive ...gymnasts (Age: 12.5 ± 1.67 y) volunteered to participate and were randomly assigned to two independent groups. The experimental plyometric training group (PTG) undertook a six-week plyometric program, involving two additional 45 min PT sessions a week, alongside their HT, while the control group (CG) performed regular HT only. Videography was used (120 Hz) in the sagittal plane to record both groups performing three HVs for both the baseline and post-intervention trials. Furthermore, participants completed a countermovement jump test (CMJ) to assess the effect of PT on functional power. Through the use of Quintic biomechanics software, significant improvements (P < 0.05) were found for the PTG for run-up velocity, take-off velocity, hurdle to board distance, board contact time, table contact time and post-flight time and CMJ height. However, there were no significant improvements on pre-flight time, shoulder angle or hip angle on the vault for the PTG. The CG demonstrated no improvement for all HV measures. A sport-specific PT intervention improved handspring vault performance measures and functional power when added to the habitual training of youth female gymnasts. The additional two hours plyometric training seemingly improved the power generating capacity of movement-specific musculature, which consequently improved aspects of vaulting performance. Future research is required to examine the whether the improvements are as a consequence of the additional volume of sprinting and jumping activities, as a result of the specific PT method or a combination of these factors.
Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood–brain barrier and off-target effects. We tested a bioengineering ...approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate (Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.
The global nitrogen cycle has been greatly perturbed by human activities resulting in elevated nitrogen deposition in many parts of the world. The threat nitrogen deposition poses to ecosystem ...function and biodiversity is increasingly recognised.
In terrestrial systems, impacts on the plant community are mainly through eutrophication and soil acidification. Interactions with secondary environmental drivers such as extreme weather and disease are also key mechanisms.
Impacts on consumers can be caused by changes in the quality or quantity of food as a result of changes in food plant chemistry or species composition, changes in vegetation structure leading to a change in the availability of prey species, nesting sites or cooled microclimates or changes in the phenology of plants leading to causing phenological asynchrony.
Primary consumers have received considerably less research attention than plants but negative impacts have been observed for both folivorous insects and pollinators. Mammal herbivores have received little research attention.
New analysis of changes in plant traits along a gradient of nitrogen deposition in the UK shows that plants pollinated by large bees were negatively associated with N deposition whilst low pH was associated with lower nectar production, reduced occurrence of plants pollinated by long‐tongued insects and a reduction in plants with larger floral units.
Very few studies have investigated the effects on secondary consumers, but those that have suggest that there are likely to be negative impacts.
This review identifies considerable knowledge gaps in the impacts of N deposition on higher tropic levels and highlights that for many groups, knowledge of N deposition impacts is patchy at best. Evidence that has been collected suggests that there are likely to be impacts on primary and secondary consumers making this a priority area for investigation.
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Abstract
Although it is accepted that perfect-merging is not a realistic outcome of collisions, some researchers state that perfect-merging simulations can still be considered as quantitatively ...reliable representations of the final stage of terrestrial planet formation. Citing the work of Kokubo & Genda, they argue that the differences between the final planets in simulations with perfect-merging and those where collisions are resolved accurately are small, and it is justified to use perfect-merging results as an acceptable approximation to realistic simulations. In this paper, we show that this argument does not stand. We demonstrate that when the mass lost during collisions is taken into account, the final masses of the planets will be so different from those obtained from perfect-merging that the latter cannot be used as an approximation. We carried out a large number of smooth particle hydrodynamics simulations of embryo–embryo collisions and determined the amount of the mass and water lost in each impact. We applied the results to collisions in a typical perfect-merging simulation and showed that even when the mass loss in each collision is as small as 10%, perfect-merging can, on average, overestimate the masses of the final planets by ∼35% and their water content by more than 18%. Our analysis demonstrates that, while perfect-merging simulations are still a powerful tool in proving concepts, they cannot be used to make predictions, draw quantitative conclusions (especially about the past history of a planetary system), or serve as a valid approximation to the simulations in which collisions are resolved accurately.
Dorrell, HF, Smith, MF, and Gee, TI. Comparison of velocity-based and traditional percentage-based loading methods on maximal strength and power adaptations. J Strength Cond Res 34(1): 46-53, ...2020-This study explored the effects of velocity-based training (VBT) on maximal strength and jump height. Sixteen trained men (22.8 ± 4.5 years) completed a countermovement jump (CMJ) test and 1 repetition maximum (1RM) assessment on back squat, bench press, strict overhead press, and deadlift, before and after 6 weeks of resistance training. Participants were assigned to VBT or percentage-based training (PBT) groups. The VBT group's load was dictated through real-time velocity monitoring, as opposed to pretesting 1RM data (PBT). No significant differences were present between groups for pretesting data (p > 0.05). Training resulted in significant increases (p < 0.05) in maximal strength for back squat (VBT 9%, PBT 8%), bench press (VBT 8%, PBT 4%), strict overhead press (VBT 6%, PBT 6%), and deadlift (VBT 6%). Significant increases in CMJ were witnessed for the VBT group only (5%). A significant interaction effect was witnessed between training groups for bench press (p = 0.004) and CMJ (p = 0.018). Furthermore, for back squat (9%), bench press (6%), and strict overhead press (6%), a significant difference was present between the total volume lifted. The VBT intervention induced favorable adaptations in maximal strength and jump height in trained men when compared with a traditional PBT approach. Interestingly, the VBT group achieved these positive outcomes despite a significant reduction in total training volume compared with the PBT group. This has potentially positive implications for the management of fatigue during resistance training.
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