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To combat declines in biodiversity, conservationists are increasingly looking to restore wildlife populations through the reintroduction of select species, the establishment of protected areas, and the use of human-wildlife conflict mitigation tools. A primary objective of wildlife restoration efforts is to reestablish trophic interactions crucial for the function and structure of ecosystems. However, recovering wildlife populations are often returning to novel ecosystems with altered environments and new species compositions. These novel ecosystems may then complicate the outcomes of wildlife restoration efforts. In Chapter 1, I provide a brief introduction to key themes of wildlife restoration in novel ecosystems. In Chapter 2, I evaluate the outcomes of wildlife translocations around the world. Specifically, I evaluate whether the inclusion of human dimensions in the planning and execution of a translocation improves success. Next, for my final two chapters, I zoom in to Argentine Patagonia to better understand how a novel environment impacts the outcomes of wildlife restoration. In Chapter 3, I assess how roads influence the habitat selection of the most widespread large herbivore in Patagonia, the guanaco. In addition to the creation of novel landscapes, habitat restoration in the region has led to a novel interaction between pumas and penguins. In Chapter 4, I test how this novel interaction between pumas and penguins impacts puma behavior and their population. Then building on these results, for Chapter 5, I examine the impacts of the puma-penguin interaction on guanacos, the primary prey for guanacos throughout Patagonia. Finally in Chapter 6, I close with some concluding remarks about wildlife restoration in novel ecosystems.

With more than 1·2 million people living with HIV in the USA, a complex epidemic across the large and diverse country, and a fragmented health-care system marked by widening health disparities, the US HIV epidemic requires sustained scientific and public health attention. The epidemic has been stubbornly persistent; high incidence densities have been sustained over decades and the epidemic is increasingly concentrated among racial, ethnic, and sexual and gender minority communities. This fact remains true despite extraordinary scientific advances in prevention, treatment, and care-advances that have been led, to a substantial degree, by US-supported science and researchers. In this watershed year of 2021 and in the face of the COVID-19 pandemic, it is clear that the USA will not meet the stated goals of the National HIV/AIDS Strategy, particularly those goals relating to reductions in new infections, decreases in morbidity, and reductions in HIV stigma. The six papers in the Lancet Series on HIV in the USA have each examined the underlying causes of these challenges and laid out paths forward for an invigorated, sustained, and more equitable response to the US HIV epidemic than has been seen to date. The sciences of HIV surveillance, prevention, treatment, and implementation all suggest that the visionary goals of the Ending the HIV Epidemic initiative in the USA might be achievable. However, fundamental barriers and challenges need to be addressed and the research effort sustained if we are to succeed.

Summary Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures.

Summary In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products.

Graphite foils with ultra-high spreading capacity and insulation sheets with ultra-low thermal conductivity were combined in a thermally stressed Google Pixel 3XL to reduce steady-state surface touch (skin) temperatures $(\mathrm{T}_{S})$ by up to $3.2 ^{\circ}\mathrm{C}$ with $\lt 1 ^{\circ}\mathrm{C}$ increase in max junction temperature $(\mathrm{T}_{J})$ as compared to single-component thermal solutions of graphite, insulation, and air. An axisymmetric conduction model was simulated in COMSOL to determine trends in surface temperature reductions of five unique thermal solutions of comparable thickness $(\sim 350 \mu \mathrm{m})$. Four of these solutions were fabricated, tested and validated experimentally in Google Pixel 3XL thermal stress testing. The composite yielding the greatest $\mathrm{T}_{S}$ reduction was utilized to demonstrate an increase in steady-state system performance while maintaining a surface temperature suitable for user safety. The steady-state 3DMark -- Sling Shot Extreme benchmark score increased from 3401 to 3823 resulting in a 12.4% increase in steady-state system performance. The enhanced device performance was linked with material properties by means of steady-state heat flow and thickness testing for through-plane thermal conductivity of insulation, and thermal diffusivity testing for in-plane thermal conductivity of graphite. In-plane conductivity of graphite was validated experimentally in a steadystate heat spreading test where $100 \mu \mathrm{m}$ foils of high-performance graphite measured $\sim30$% higher spreading capacity than $100 \mu \mathrm{m}$ foils of synthetic and natural graphite.

In response to World Health Organization (WHO) guidance recommending oral pre-exposure prophylaxis (PrEP) for all individuals at substantial risk for HIV infection, significant investments are being made to expand access to oral PrEP globally, particularly in sub-Saharan Africa. Some have interpreted early monitoring reports from new programs delivering oral PrEP to adolescent girls and young women (AGYW) as suggestive of low uptake. However, a lack of common definitions complicates interpretation of oral PrEP uptake and coverage measures, because various indicators with different meanings and uses are used interchangeably. Furthermore, operationalising these measures in real-world settings is challenged by the difficulties in defining the denominator for measuring uptake and coverage among AGYW, due to the lack of data and experience required to identify the subset of AGYW at substantial risk of HIV infection. This paper proposes an intervention-centric cascade as a framework for developing a common lexicon of metrics for uptake and coverage of oral PrEP among AGYW. In codifying these indicators, approaches to clearly define metrics for uptake and coverage are outlined, and the discussion on ‘low’ uptake is reframed to focus on achieving the highest possible proportion of AGYW using oral PrEP when they need and want it Recommendations are also provided for making increased investments in implementation research to better quantify the sub-group of AGYW in potential need of oral PrEP.and for improving monitoring systems to more efficiently address bottlenecks in the service delivery of oral PrEP to AGYW so that implementation can be taken to scale.

The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, "From Research to Impact," acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21-25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website. Supported by Gilead who provided funding. Gilead has had no input into the content of the materials used at this meeting/conference. No other pharmaceutical company has had input into the content of the materials used at this conference. HIVR4P 2018 was made possible in part by 1 R13 AI136762-01 from the National Institute of Allergy and Infectious Diseases (NIAID). The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. Sí

Summary Although effective programmes are available and several countries have seen substantial declines in new HIV infections, progress in the reduction of adult HIV incidence has been slower than expected worldwide and many countries have not had large decreases in new infections in adults despite large reductions in paediatric infections. Reasons for slow progress include inadequate commitment, investment, focus, scale, and quality of implementation of prevention and treatment interventions. The UNAIDS–Lancet Commission on Defeating AIDS—Advancing Global Health reported that the provision of large-scale, effective HIV prevention programmes has failed and called on stakeholders to "get serious about HIV prevention". An ambitious worldwide target has been set by UNAIDS to reduce new infections below 500 000 by 2020—a 75% reduction from 2010. Models show that such a reduction requires a combination of primary prevention interventions and preventative effects of treatment. Achievement of the target will require more effective delivery of HIV prevention for sufficient coverage in populations at greatest risk of infection ensuring that interventions that have proved effective are made available, barriers to their uptake are overcome, demand is created, and use is consistent and occurs at the right scale with high coverage. This paper discusses how programmatic targets for prevention in a worldwide plan could be used to re-energise the HIV prevention approach. A management framework is proposed outlining global, regional, national, and subnational actions and is summarised in a call for action on HIV prevention for 2020.

© 2017 Barbara L. Shacklett t al. HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17-21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme "Partnering for Prevention" represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org.

Parental care (e.g. provisioning nestlings) is widely assumed to be costly, and life-history theory predicts a trade-off between reproduction and future fecundity and/or survival. However, experimental studies manipulating workload during parental care and demonstrating fitness effects are either rare or have mixed results. Here, we took a two-step approach to this problem in European starlings (Sturnus vulgaris): 1) using a 4-year dataset to ask if changes in parental investment in handicapped (wing-clipped) parents, and the fitness consequences of these decisions, vary among years (i.e. with ecological context), and 2) using an automated radio telemetry system to determine if females alter their activity to compensate for an increase in workload. We found marked individual and annual variation in response to the handicapping treatment. In addition, clipped individuals dramatically reduced their activity, while sustaining current breeding productivity, suggesting that clipped individuals reduce self-maintenance to favour their current reproductive bout.

The successful demonstration that antiretroviral (ARV) drugs can be used in diverse ways to reduce HIV acquisition or transmission risks – either taken as pre-exposure prophylaxis (PrEP) by those who are uninfected or as early treatment for prevention (T4P) by those living with HIV – expands the armamentarium of existing HIV prevention tools. These findings have implications for the design of future HIV prevention research trials. With the advent of multiple effective HIV prevention tools, discussions about the ethics and the feasibility of future HIV prevention trial designs have intensified. This article outlines arguments concerning the inclusion of newly established ARV-based HIV prevention interventions as standard of prevention in HIV prevention trials from multiple perspectives. Ultimately, there is a clear need to incorporate stakeholders in a robust discussion to determine the appropriate trial design for each study population.

This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process. (c) 2007 Lippincott Williams & Wilkins.

Introduction After the initial approval of the use of tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) by the US Food and Drug Administration in 2012 for anti-HIV pre-exposure prophylaxis (PrEP), uptake was initially limited, but more recent community surveys and expert opinion suggest wider acceptance in some key populations. Discussion Demonstration projects are underway to determine the best practices in the United States to identify at-risk individuals in primary care and sexually transmitted disease clinics who could benefit from PrEP. Studies of PrEP in combination with behavioural interventions are being evaluated. Studies to evaluate the use of PrEP by HIV-uninfected women in HIV-discordant couples interested in safe conception are also getting underway. The optimal deployment of PrEP as part of a comprehensive national HIV/AIDS strategy in the United States has been limited by lack of knowledge among some at-risk people and by some medical providers indicating that they do not feel sufficiently knowledgeable and comfortable in prescribing PrEP. Studies are underway to determine how to assist busy clinicians to determine which of their patients could benefit from PrEP. Although most federal health insurance programmes will cover most of the costs associated with PrEP, underinsured patients in states that have not enacted health reform face additional challenges in paying for PrEP medication and appropriate clinical monitoring. Conclusions PrEP implementation in the United States is a work in progress, with increasing awareness and uptake among some individuals in key populations.

Activist groups have been successful in promoting research and better treatment for people with HIV infection, but they can also stop trials if their views are not considered Methods to prevent HIV infection are one of the most urgent global public health needs.1 One novel method in clinical trials is pre-exposure prophylaxis with the antiretroviral drug tenofovir. The trials have, however, been criticised by activist groups, citing human rights, ethical concerns, and a lack of community involvement.2 This opposition and media coverage has stopped two trials in Cambodia and Cameroon and threatens the stability of planned and recruiting trials among intravenous drug users in Thailand and other developing nations. The issues raised by activists, academics, and the research community highlight the poor communication between these stakeholders and the need for mutual understanding of values. The differences threaten to undermine the progress of prevention trials and ultimately affect the most important stakeholders, those who are at risk.3 This protest at the 2004 International AIDS Society Conference helped stop the Cambodian tenofovir trialCredit: STR/AFP/GETTY IMAGES ### Cambodia The first randomised trial planned to assess the safety and efficacy of prophylactic tenofovir was in Phnom Penh, Cambodia. The study, funded by the US National Institutes of Health and the Bill and Melinda Gates Foundation, planned to recruit 960 sex workers and was led by researchers from the United States and Australia.3 In July 2004, activists mounted the first large demonstration against the trial at the Gilead booth at the International AIDS Society conference in Bangkok, a protest that captured the world's media attention.4 This protest, as well as local remonstration to the Ministry of Health in Cambodia, resulted in the Cambodian prime minister closing the trial before recruitment. The government has provided no official reasons for its decision. The primary …

Although the female condom has been introduced into over 90 countries since 1997, it has only been accepted in sexual and reproductive health programmes as a mainstream method in a few. This paper describes introductory strategies developed by Ministries of Health and non-governmental organisations in Brazil, Ghana, Zimbabwe and South Africa, supported by UNAIDS, and the manufacturers of the female condom, which have significantly expanded the number of female condoms being used. These projects have several key similarities: a focus on training for providers and peer educators, face-to-face communication with potential users to equip them with information and skills, an identified target audience, a consistent supply, a long assessment period to gauge actual use beyond the initial novelty phase, and a mix of public and private sector distribution. Female condom programmes require the sanction, leadership and funding of governments and donors. However, the non-governmental and private sectors have also played a major role in programme implementation. To ensure successful introduction of the female condom, it is crucial to involve a range of decision-makers, programme managers, service providers, community leaders and women's and youth groups. The rising cost of inaction and unprotected sex in the spread of HIV and AIDS force us to recognise the high cost of not providing female condoms alongside male condoms in family planning and AIDS prevention programmes.

Introduction : The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. Methods and Results : The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation – reaching 18 million people with antiviral therapy by mid-year 2016. Yet incident HIV infections in adults remain stubbornly stable and are increasing in some regions and among adolescents and adults in some key populations, challenging current science, policy and programming. There have been important advances in both preventive vaccines and in cure research, but both areas require ongoing investment and innovation. Clinical research has flourished with new agents, regimens, delivery modes and diagnostics but has been challenged by aging and increasingly complex patient populations, long-term adherence challenges, co-infections and co-morbidities, and unresolved issues in TB management and epidemic control. It is an extraordinary period of innovation in prevention, yet the promise of new tools and combination approaches have yet to deliver epidemic HIV control. Conclusions : Proven interventions, most notably pre-exposure prophylaxis, PrEP, have been limited in rollout and impact. Treatment as prevention has the promise to improve clinical outcomes but remains uncertain as a prevention tool to reduce population-level HIV incidence. The improvement of legal, policy and human rights environments for those most at risk for HIV acquisition and most at risk for lack of access to essential services; sexual and gender minorities, sex workers of all genders, people who inject drugs, and prisoners and detainees remain among the greatest unmet needs in HIV/AIDS. Failure to do better for these individuals and communities could undermine the HIV response. Keywords HIV; treatment; prevention; vaccines; human rights; implementation science (Published: 30 June 2017) Beyrer C et al. Journal of the International AIDS Society 2017, 20 :21781 http://www.jiasociety.org/index.php/jias/article/view/21781 | http://dx.doi.org/10.7448/IAS.20.1.21781

Background The Investment Framework Enhanced (IFE) proposed in 2013 by the Joint United Nations Programme on HIV/AIDS (UNAIDS) explored how maximizing existing interventions and adding emerging prevention options, including a vaccine, could further reduce new HIV infections and AIDS-related deaths in low- and middle-income countries (LMICs). This article describes additional modeling which looks more closely at the potential health impact and cost-effectiveness of AIDS vaccination in LMICs as part of UNAIDS IFE. Methods An epidemiological model was used to explore the potential impact of AIDS vaccination in LMICs in combination with other interventions through 2070. Assumptions were based on perspectives from research, vaccination and public health experts, as well as observations from other HIV/AIDS interventions and vaccination programs. Sensitivity analyses varied vaccine efficacy, duration of protection, coverage, and cost. Results If UNAIDS IFE goals were fully achieved, new annual HIV infections in LMICs would decline from 2.0 million in 2014 to 550,000 in 2070. A 70% efficacious vaccine introduced in 2027 with three doses, strong uptake and five years of protection would reduce annual new infections by 44% over the first decade, by 65% the first 25 years and by 78% to 122,000 in 2070. Vaccine impact would be much greater if the assumptions in UNAIDS IFE were not fully achieved. An AIDS vaccine would be cost-effective within a wide range of scenarios. Interpretation Even a modestly effective vaccine could contribute strongly to a sustainable response to HIV/AIDS and be cost-effective, even with optimistic assumptions about other interventions. Higher efficacy would provide even greater impact and cost-effectiveness, and would support broader access. Vaccine efficacy and cost per regimen are critical in achieving cost-effectiveness, with cost per regimen being particularly critical in low-income countries and at lower efficacy levels.