Biocompatible gold nanoparticles designed to absorb light at wave-lengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles ...to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.
Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and ...their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter‐period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world's seasonally freezing lakes and seas.
Plain Language Summary
The Laurentian Great Lakes are the world's largest freshwater ecosystem and provide diverse ecosystem services to millions of people. Affected by multiple interacting stressors, this system is the target of extensive restoration and management efforts that demand robust scientific knowledge. Winter limnology represents a key knowledge gap that limits understanding and prediction of the function of the Great Lakes and other large temperate lakes. Here, we summarize what is known about the Great Lakes during their 3–6 months of winter, identify key questions that must be addressed to improve understanding of the physical, chemical, and biological functioning of large lakes in winter, and suggest ways to address these questions. We show that ice cover is a “master variable” that controls numerous aspects of large temperate lake ecology and that the effects of the ongoing reduction in ice cover extent and duration cannot be predicted without improved knowledge of winter limnology.
Key Points
Winter limnology is a key knowledge gap that limits understanding and management of the Great Lakes and other large, seasonally frozen lakes
We review the winter physics, chemistry, and biology of the Great Lakes and identify priority questions for winter research on large lakes
Ice cover is a “master variable” for many large lake limnological processes, making a better understanding of its role a research priority
cSCC is increasing in prevalence due to increased lifespans and improvements in survival for conditions that increase the risk of cSCC. The absolute mortality of cSCC exceeds melanoma in the United ...States and approaches that of melanoma worldwide. This review presents significant changes in the management of cSCC, focusing on improvements in risk stratification, new treatment options, optimization of existing treatments, and prevention strategies. One major breakthrough in cSCC treatment is the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), which have ushered in a renaissance in the treatment of patients with locally advanced and metastatic disease. These agents have offered patients with advanced disease decreased therapeutic toxicity compared to traditional chemotherapy agents, a more durable response after discontinuation, and improved survival. cSCC is an active field of research, and this review will highlight some of the novel and more developed clinical trials that are likely to impact cSCC management in the near future.
Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary ...versus recurrent tumor, anatomic location, size, and patient attributes determine the risk level and acceptable treatment options. Surgical options offer histologic confirmation of tumor clearance. Standard excision provides post-treatment histologic assessment, while Mohs micrographic surgery (MMS) provides complete margin assessment intraoperatively. Additional treatment options may be employed in the correct clinical context. Small and low-risk BCCs, broad field cancerization, locally-advanced disease, metastatic disease, cosmetic concerns, or morbidity with surgical approaches raise consideration of other treatment modalities. We review herein a range of treatment approaches and advances in treatments for BCC, including standard excision, MMS, electrodesiccation and curettage, ablative laser treatment, radiation therapy, targeted molecular therapies, topical therapies, field therapies, immunotherapy, and experimental therapies.
In what follows, I will canvas the popular theories of human welfare, and compare them to potential counterpart theories for nonhuman animals. Broadly I will assess three views of welfare: hedonism, ...preference-based theories, and objective list theories. As is well known in the literature, all three of these views have their strengths and flaws, but what I will try to show is that the strengths and flaws of each theory shift when thinking about different kinds of nonhuman animals. Because of this, some theories fit better with certain types of creatures, while other theories fit best with other types of creatures. However, no single theory of welfare that we examine is an appropriate fit for all welfare subjects, and so I will ultimately argue that we should adopt a variabilist (or hybrid) conception of welfare when thinking about nonhuman animals. In particular, I argue that we should give greater weight to the hedonistic elements of welfare when the welfare subjects under consideration have lower levels of cognitive and emotional complexity. As cognitive and emotional complexity increase, we should put more weight on the satisfaction of preferences. This view will provide nuance not provided by other views, and this allows us to approach ethical issues, like the permissibility and requirements of pet ownership, from a different angle than previously.
Direct measurements of rates of primary production in Lake Erie are few and uncertainties surround rate measurements based on radiocarbon and the light-dark bottle incubation methods. For these ...reasons, we conducted a series of simultaneous primary productivity measurements in Lake Erie in July and August of 2003, based on incubation with ¹⁴C-NaHCO₃, the light-dark bottle method, and incubation with ¹⁸O enriched water. Significant differences in the rates of primary production obtained by incubations with ¹⁸O-H₂O (0.19-34.60 mmol-O₂ m-³ h-¹), ¹⁴C-NaHCO₃ (0.03-90.50 mmol-C m-³ h-¹), and light-dark bottles (0.06-60.78 mmol-O₂ m-³ h-¹) were evident in six out of nine comparisons. Within the epilimnion, ¹⁸O-H₂O rates of primary production were significantly different from rates based on ¹⁴C-NaHCO₃ and light-dark bottles in all four comparisons and lower rates were obtained in three out of four comparisons. Eutrophic conditions in Sandusky Bay, Lake Erie were evident from the high primary production rates of 20.50-34.60 mmol-O₂ m-³ h-¹ (¹⁸O-H₂O), 34.39-90.50 mmol-C m-³ h-¹ (¹⁴C-NaHCO₃), and 46.66-60.78 mmol-O₂ m-³ h-¹ (light-dark bottle). The photosynthetic quotient (PQ), or ratio of O₂ production to CO₂ consumption during photosynthesis, averaged 0.64±0.33 and 1.93±1.93, respectively, based on a comparison of ¹⁸O-H₂O to ¹⁴C-NaHCO₃ rates or light-dark bottle to ¹⁴C-NaHCO₃ production rates, respectively, demonstrating that photosynthesis in Lake Erie communities primarily follows expected stochiometric trends. The average of the ratio of production rates based on incubation with ¹⁸O-H₂O relative to those obtained by the light-dark incubation method was 0.66±0.33, indicating a tendency for the ¹⁸O-H₂O method to provide slightly lower estimates of production in Lake Erie. Lower estimates of primary production based on ¹⁸O-H₂O incubation relative to the other two approaches is most likely a consequence of consumption of labeled O₂ within the cell or dilution of label by the release of O₂ from supersaturated cells. This latter effect may be particularly characteristic of eutrophic environments.
Trauma is the leading cause of death for US individuals younger than 45 years, and uncontrolled hemorrhage is a major cause of trauma mortality. The US military's medical advancements in the field of ...prehospital hemorrhage control have reduced battlefield mortality by 44%. However, despite support from many national health care organizations, no integrated approach to research has been made regarding implementation, epidemiology, education, and logistics of prehospital hemorrhage control by layperson immediate responders in the civilian sector.
To create a national research agenda to help guide future work for prehospital hemorrhage control by laypersons.
The 2-day, in-person, National Stop the Bleed (STB) Research Consensus Conference was conducted on February 27 to 28, 2019, to identify and achieve consensus on research gaps. Participants included (1) subject matter experts, (2) professional society-designated leaders, (3) representatives from the federal government, and (4) representatives from private foundations. Before the conference, participants were provided a scoping review on layperson prehospital hemorrhage control. A 3-round modified Delphi consensus process was conducted to determine high-priority research questions. The top items, with median rating of 8 or more on a Likert scale of 1 to 9 points, were identified and became part of the national STB research agenda.
Forty-five participants attended the conference. In round 1, participants submitted 487 research questions. After deduplication and sorting, 162 questions remained across 5 a priori-defined themes. Two subsequent rounds of rating generated consensus on 113 high-priority, 27 uncertain-priority, and 22 low-priority questions. The final prioritized research agenda included the top 24 questions, including 8 for epidemiology and effectiveness, 4 for materials, 9 for education, 2 for global health, and 1 for health policy.
The National STB Research Consensus Conference identified and prioritized a national research agenda to support laypersons in reducing preventable deaths due to life-threatening hemorrhage. Investigators and funding agencies can use this agenda to guide their future work and funding priorities.
Predicting ecological effects of contaminants remains challenging because of the sheer number of chemicals and their ambiguous role in biodiversity-ecosystem function relationships. We evaluate ...responses of experimental pond ecosystems to standardized concentrations of 12 pesticides, nested in four pesticide classes and two pesticide types. We show consistent effects of herbicides and insecticides on ecosystem function, and slightly less consistent effects on community composition. Effects of pesticides on ecosystem function are mediated by alterations in the abundance and community composition of functional groups. Through bottom-up effects, herbicides reduce respiration and primary productivity by decreasing the abundance of phytoplankton. The effects of insecticides on respiration and primary productivity of phytoplankton are driven by top-down effects on zooplankton composition and abundance, but not richness. By demonstrating consistent effects of pesticides on communities and ecosystem functions and linking pesticide-induced changes in functional groups of organisms to ecosystem functions, the study suggests that ecological risk assessment of registered chemicals could be simplified to synthetic chemical classes or types and groups of organisms with similar functions and chemical toxicities.
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