Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles.

Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20-hydroxyecdysone (20E), remains largely unknown. Here we show that Plasmodium falciparum development is intimately but not competitively linked to processes shaping Anopheles gambiae reproduction. We unveil a 20E-mediated positive correlation between egg and oocyst numbers; impairing oogenesis by multiple 20E manipulations decreases parasite intensities. These manipulations, however, accelerate Plasmodium growth rates, allowing sporozoites to become infectious sooner. Parasites exploit mosquito lipids for faster growth, but they do so without further affecting egg development. These results suggest that P. falciparum has adopted a non-competitive evolutionary strategy of resource exploitation to optimize transmission while minimizing fitness costs to its mosquito vector. Our findings have profound implications for currently proposed control strategies aimed at suppressing mosquito populations.

A male steroid controls female sexual behaviour in the malaria mosquito.

Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones1. In the malaria mosquito Anopheles gambiae, the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females2 and to induce mating refractoriness when sexually transferred by males3. Because egg development and mating are essential reproductive traits, understanding how Anopheles females integrate these hormonal signals can spur the design of new malaria control programs. Here we reveal that these reproductive functions are regulated by distinct sex steroids through a sophisticated network of ecdysteroid-activating/inactivating enzymes. We identify a male-specific oxidized ecdysteroid, 3-dehydro-20E (3D20E), which safeguards paternity by turning off female sexual receptivity following its sexual transfer and activation by dephosphorylation. Notably, 3D20E transfer also induces expression of a reproductive gene that preserves egg development during Plasmodium infection, ensuring fitness of infected females. Female-derived 20E does not trigger sexual refractoriness but instead licenses oviposition in mated individuals once a 20E-inhibiting kinase is repressed. Identifying this male-specific insect steroid hormone and its roles in regulating female sexual receptivity, fertility and interactions with Plasmodium parasites suggests the possibility for reducing the reproductive success of malaria-transmitting mosquitoes.

Precise coordination between nutrient transporters ensures fertility in the malaria mosquito Anopheles gambiae.

Females from many mosquito species feed on blood to acquire nutrients for egg development. The oogenetic cycle has been characterized in the arboviral vector Aedes aegypti, where after a bloodmeal, the lipid transporter lipophorin (Lp) shuttles lipids from the midgut and fat body to the ovaries, and a yolk precursor protein, vitellogenin (Vg), is deposited into the oocyte by receptor-mediated endocytosis. Our understanding of how the roles of these two nutrient transporters are mutually coordinated is however limited in this and other mosquito species. Here, we demonstrate that in the malaria mosquito Anopheles gambiae, Lp and Vg are reciprocally regulated in a timely manner to optimize egg development and ensure fertility. Defective lipid transport via Lp knockdown triggers abortive ovarian follicle development, leading to misregulation of Vg and aberrant yolk granules. Conversely, depletion of Vg causes an upregulation of Lp in the fat body in a manner that appears to be at least partially dependent on target of rapamycin (TOR) signaling, resulting in excess lipid accumulation in the developing follicles. Embryos deposited by Vg-depleted mothers are completely inviable, and are arrested early during development, likely due to severely reduced amino acid levels and protein synthesis. Our findings demonstrate that the mutual regulation of these two nutrient transporters is essential to safeguard fertility by ensuring correct nutrient balance in the developing oocyte, and validate Vg and Lp as two potential candidates for mosquito control.

Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies.

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.

Multiple blood feeding in mosquitoes shortens the Plasmodium falciparum incubation period and increases malaria transmission potential.

Many mosquito species, including the major malaria vector Anopheles gambiae, naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time. We measured P. falciparum oocyst size and performed sporozoite time course analyses to determine the parasite's extrinsic incubation period (EIP), i.e. the time required by parasites to reach infectious sporozoite stages, in An. gambiae females blood fed either once or twice. An additional blood feed at 3 days post infection drastically accelerates oocyst growth rates, causing earlier sporozoite accumulation in the salivary glands, thereby shortening the EIP (reduction of 2.3 ± 0.4 days). Moreover, parasite growth is further accelerated in transgenic mosquitoes with reduced reproductive capacity, which mimic genetic modifications currently proposed in population suppression gene drives. We incorporate our shortened EIP values into a measure of transmission potential, the basic reproduction number R0, and find the average R0 is higher (range: 10.1%-12.1% increase) across sub-Saharan Africa than when using traditional EIP measurements. These data suggest that malaria elimination may be substantially more challenging and that younger mosquitoes or those with reduced reproductive ability may provide a larger contribution to infection than currently believed. Our findings have profound implications for current and future mosquito control interventions.

A mating-induced reproductive gene promotes Anopheles tolerance to Plasmodium falciparum infection.

Anopheles mosquitoes have transmitted Plasmodium parasites for millions of years, yet it remains unclear whether they suffer fitness costs to infection. Here we report that the fecundity of virgin and mated females of two important vectors-Anopheles gambiae and Anopheles stephensi-is not affected by infection with Plasmodium falciparum, demonstrating that these human malaria parasites do not inflict this reproductive cost on their natural mosquito hosts. Additionally, parasite development is not impacted by mating status. However, in field studies using different P. falciparum isolates in Anopheles coluzzii, we find that Mating-Induced Stimulator of Oogenesis (MISO), a female reproductive gene strongly induced after mating by the sexual transfer of the steroid hormone 20-hydroxyecdysone (20E), protects females from incurring fecundity costs to infection. MISO-silenced females produce fewer eggs as they become increasingly infected with P. falciparum, while parasite development is not impacted by this gene silencing. Interestingly, previous work had shown that sexual transfer of 20E has specifically evolved in Cellia species of the Anopheles genus, driving the co-adaptation of MISO. Our data therefore suggest that evolution of male-female sexual interactions may have promoted Anopheles tolerance to P. falciparum infection in the Cellia subgenus, which comprises the most important malaria vectors.

Replication of Marek's disease vaccines in turkey embryos and their effect on TLR-3 and IFN-γ transcripts.

Understanding the pathogenesis of herpesvirus of turkeys (HVT) in its natural host is necessary before recombinant HVT (rHVT) can be used efficiently in turkey flocks. The objectives of this study were to evaluate when commercial turkey flocks get infected with wild type HVT, to study replication of HVT (conventional and recombinant rHVT-Newcastle disease, rHVT-ND) and other Marek's disease (MD) vaccines (SB-1 and CVI988) in turkey embryonic tissues, and to evaluate the expression of TLR-3 and IFN-γ in the lung and spleen of one-day-old turkeys after in ovo vaccination with MD vaccines. Our results demonstrated that commercial turkeys got exposed to wild type HVT within the first days of life; therefore, there is a potential of interaction between wild type HVT and rHVT when administered at day of age. On the other hand, all evaluated vaccines (especially HVT and rHVT-ND) replicated very well in turkey embryonic tissues. In ovo vaccination with HVT and CVI988 increased transcription of TLR-3 in the spleen of one-day-old turkeys. However, no effect on the transcription of TLR-3 or IFN-γ in the lungs and IFN-γ in the spleen in newly hatched turkeys was detected in the present study. Because of the limitations of evaluated genes, timepoints, and studied tissues, future studies are warranted to better understand the effect of MD vaccines on the turkey embryo immune responses.RESEARCH HIGHLIGHTS Commercial turkey flocks get infected with wild type HVT within the first days of life.HVT and rHVT replicates readily in turkey embryonic tissues.SB-1 and CVI988 also replicate in turkey embryonic tissues, but at lower rates than HVT and rHVT.HVT and CVI988 increase transcription of TLR-3 in the spleen.

Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care.

Purpose To evaluate whether a protocol for early intervention addressing the psychosocial risk factors for delayed return to work in workers with soft tissue injuries would achieve better long-term outcomes than usual (stepped) care. Methods The study used a controlled, non-randomised prospective design to compare two case management approaches. For the intervention condition, workers screened within 1-3 weeks of injury as being at high risk of delayed returned to work by the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) were offered psychological assessment and a comprehensive protocol to address the identified obstacles for return to work. Similarly identified injured workers in the control condition were managed under usual (stepped) care arrangements. Results At 2-year follow-up, the mean lost work days for the Intervention group was less than half that of the usual care group, their claim costs were 30% lower, as was the growth trajectory of their costs after 11 months. Conclusions The findings supported the hypothesis that brief psychological risk factor screening, combined with a protocol for active collaboration between key stakeholders to address identified psychological and workplace factors for delayed return to work, can achieve better return on investment than usual (stepped) care.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: dental anomalies in 8-year olds.

BACKGROUND: Children born with unilateral cleft lip and palate (UCLP) are reported to display several dental anomalies including agenesis, supernumeraries, as well as variations in dental size, shape, and path of eruption. The extensive sample of individuals with UCLP included in the Scandcleft randomized control trials offers the opportunity to study more rare conditions, which is seldom possible with limited samples. OBJECTIVES: The aim was to study dental anomalies at 8 years of age in children born with UCLP included in the Scandcleft randomized control trials. METHODS: Panoramic and intraoral radiographs from 425 individuals (279 males and 146 females) with a mean age of 8.1 years were assessed by four orthodontists regarding dental anomalies. RESULTS: Agenesis was found in 52.5 per cent and supernumerary teeth in 16.9 per cent of the participants. The cleft lateral was missing in 43.8 per cent and was found peg shaped in 44.7 per cent. The distribution of ectopic eruption was 14.6 per cent, mainly affecting maxillary first molars, while transposition was found in 3.4 per cent of the individuals. In addition, infraocclusion of one or several primary molars was registered in 7.2 per cent of the participants. CONCLUSION: We conclude that 8-year-old children born with UCLP display multiple dental anomalies. The Scandcleft sample allowed rarely studied conditions such as infraocclusion of primary molars and transposition to be studied in children born with UCLP. TRIAL REGISTRATION: ISRCTN29932826.

Predicting Return to Work in a Heterogeneous Sample of Recently Injured Workers Using the Brief ÖMPSQ-SF.

Purpose (1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification. Methods Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5-15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2-7 weeks. Results The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2-7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79). Conclusion The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type.

Correction to: Implementation of Early Intervention Protocol in Australia for 'High Risk' Injured Workers is Associated with Fewer Lost Work Days Over 2 Years Than Usual (Stepped) Care.

The original version of this article unfortunately contained a spelling error in one of the co-authors's names. The family name of the co-author was incorrectly displayed as "James McCauley" instead of "James McAuley. The original article has been corrected.

Valuing the Benefits of Rock Climbing and the Welfare Gains from Decreasing Injury Risk.

Rock climbing is an increasingly popular recreation activity worldwide, nevertheless there are only few studies that estimate the demand for it. In this article the Kuhn-Tucker approach is used to estimate the demand for rock climbing in Sicily, the recreation value of different climbing sites, and the welfare impact of reducing injury risk. In modeling the demand for climbing we account for the heterogeneity of preferences. We find that decreasing the level of injury risk generates remarkable welfare gains to climbers. This is the first study we know of that provides a welfare measure of risk reduction in rock climbing and one of a very few studies in environmental economics that uses a revealed preference approach to estimate a welfare measure associated with a reduction in risk.

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae.

Anopheles gambiae mosquitoes are major African vectors of malaria, a disease that kills more than 600,000 people every year. Given the spread of insecticide resistance in natural mosquito populations, alternative vector control strategies aimed at reducing the reproductive success of mosquitoes are being promoted. Unlike many other insects, An. gambiae females mate a single time in their lives and must use sperm stored in the sperm storage organ, the spermatheca, to fertilize a lifetime's supply of eggs. Maintenance of sperm viability during storage is therefore crucial to the reproductive capacity of these mosquitoes. However, to date, no information is available on the factors and mechanisms ensuring sperm functionality in the spermatheca. Here we identify cellular components and molecular mechanisms used by An. gambiae females to maximize their fertility. Pathways of energy metabolism, cellular transport, and oxidative stress are strongly regulated by mating in the spermatheca. We identify the mating-induced heme peroxidase (HPX) 15 as an important factor in long-term fertility, and demonstrate that its function is required during multiple gonotrophic cycles. We find that HPX15 induction is regulated by sexually transferred 20-hydroxy-ecdysone (20E), a steroid hormone that is produced by the male accessory glands and transferred during copulation, and that expression of this peroxidase is mediated via the 20E nuclear receptor. To our knowledge, our findings provide the first evidence of the mechanisms regulating fertility in Anopheles, and identify HPX15 as a target for vector control.

Implementation of the Participatory Approach for Supervisors to Increase Self-Efficacy in Addressing Risk of Sick Leave of Employees: Results of a Cluster-Randomized Controlled Trial.

Purpose To study the effectiveness of a multifaceted strategy to implement the participatory approach (PA) for supervisors to increase their self-efficacy in addressing risk of sick leave of employees. Methods Supervisors from three organizations were invited to participate. Randomization was performed at department level. Supervisors (n = 61) in the intervention departments received the implementation strategy consisting of a working group meeting, supervisor training in PA application, and optional supervisor coaching. Supervisors in the control departments (n = 55) received written information on PA. The primary outcome was supervisors' self-efficacy to apply the PA, measured at baseline and 6 months' follow-up. The number of employees with whom supervisors discussed work functioning problems or (risk of) sick leave was also assessed. Effects were tested using multilevel analyses. Results The strategy did not increase self-efficacy to apply the PA. Subgroup analyses showed that self-efficacy increased for supervisors who at baseline reported to have discussed (risk of) sick leave with less than three employees during the last 6 months (B = 1.42, 95 % CI 0.34-2.50). Furthermore, the implementation strategy increased the number of employees with whom supervisors discussed work functioning problems or risk of sick leave (B = 1.26, 95 % CI 0.04-2.48). Conclusion Although the implementation strategy cannot be recommended for all supervisors, for supervisors who less frequently discuss (risk of) sick leave with employees the implementation strategy might be helpful. Trial registration NTR3733.

Employees' Perceptions of Social Norms as a Result of Implementing the Participatory Approach at Supervisor Level: Results of a Randomized Controlled Trial.

Purpose A multifaceted implementation strategy was targeted at supervisors to encourage them to apply a participatory approach (PA) in dealing with employees' work functioning problems due to health concerns. This paper assesses the effect on employees' perceived social norms regarding the use of the PA to deal with work functioning problems. Methods Three organizations participated in a cluster randomized controlled trial, with randomization at the department level. Supervisors in the PA intervention departments received the implementation strategy consisting of a working group meeting, supervisor training, and optional coaching. Supervisors in the control departments received written information about the PA only. In two of the organizations, employees were invited to complete surveys at baseline and at 6-month follow-up. The primary outcome was perceived social norms regarding the use of the PA to deal with work functioning problems. Secondary measures included attitudes and self-efficacy, and intention regarding joint problem solving, and sick leave data. Effects were analyzed using multilevel analyses to account for nesting of cases. Results At baseline, 273 employees participated in the survey, with follow-up analyses of 174 employees. There were no statistically significant group effects on employee outcome measures. The intervention group showed a larger reduction in mean sick days (from 4.6 to 2.4 days) versus the control group (from 3.8 to 3.6 days), but this difference did not reach statistical significance (p > .05). Conclusion The multifaceted strategy to implement the participatory approach for supervisors did not show effects on outcomes at the employee level. To gain significant effects at the employee level, may require that an implementation strategy not only targets management and supervisors, but also employees themselves. TRIAL REGISTRATION: NTR3733.

Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes.

AIMS: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. METHODS: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. RESULTS: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. CONCLUSIONS: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.

An historical perspective on health-risk awareness and unhealthy behaviour: cigarette smoking in the United States 1949-1981.

OBJECTIVE: This paper investigates the change through time in the perception of smoking-related health harm and smoking behaviour from 1949 to 1981. BACKGROUND AND CONTEXT: A variety of common behaviours can be linked to chronic disease risk-smoking, over-eating, and excessive sitting, to name a few. Changing behaviours to reduce exposure to such risks can be an effort that spans generations and decades. SETTING AND PARTICIPANTS: Respondents to Gallup Poll surveys in the United States from 1949, 1954, 1957, 1971, 1972, 1977 and 1981. METHODS: Graphical analysis and probit regression are used to investigate trends through time and statistical associations of smoking with the perception of smoking-related health risks and other socio-demographic variables. INTERVENTION AND MAIN VARIABLE STUDIED: Perceived smoking health risk. MAIN OUTCOME MEASURE: Smoking participation. RESULTS AND CONCLUSION: Our findings include the proportions of individuals who were self-reported smokers fell between 1949 and 1981, from 0.48 to 0.34. Among smokers, the proportion who believed smoking was harmful increased from 0.52 in 1949 to 0.81 in 1981. By 1981, the proportion of non-smokers who believed smoking was harmful was 0.98. A negative association between belief in smoking harm and the decision to smoke was shown in regression analysis. This association became more pronounced over the three decades under study.

CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males.

Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.

Development of circulating isolates of Plasmodium falciparum is accelerated in Anopheles vectors with reduced reproductive output.

Anopheles gambiae and its sibling species Anopheles coluzzii are the most efficient vectors of the malaria parasite Plasmodium falciparum. When females of these species feed on an infected human host, oogenesis and parasite development proceed concurrently, but interactions between these processes are not fully understood. Using multiple natural P. falciparum isolates from Burkina Faso, we show that in both vectors, impairing steroid hormone signaling to disrupt oogenesis leads to accelerated oocyst growth and in a manner that appears to depend on both parasite and mosquito genotype. Consistently, we find that egg numbers are negatively linked to oocyst size, a metric for the rate of oocyst development. Oocyst growth rates are also strongly accelerated in females that are in a pre-gravid state, i.e. that fail to develop eggs after an initial blood meal. Overall, these findings advance our understanding of mosquito-parasite interactions that influence P. falciparum development in malaria-endemic regions.

Ecosystems, ecological restoration, and economics: does habitat or resource equivalency analysis mean other economic valuation methods are not needed?

Coastal and other area resources such as tidal wetlands, seagrasses, coral reefs, wetlands, and other ecosystems are often harmed by environmental damage that might be inflicted by human actions, or could occur from natural hazards such as hurricanes. Society may wish to restore resources to offset the harm, or receive compensation if this is not possible, but faces difficult choices among potential compensation projects. The optimal amount of restoration efforts can be determined by non-market valuation methods, service-to-service, or resource-to-resource approaches such as habitat equivalency analysis (HEA). HEA scales injured resources and lost services on a one-to-one trade-off basis. Here, we present the main differences between the HEA approach and other non-market valuation approaches. Particular focus is on the role of the social discount rate, which appears in the HEA equation and underlies calculations of the present value of future damages. We argue that while HEA involves elements of economic analysis, the assumption of a one-to-one trade-off between lost and restored services sometimes does not hold, and then other non-market economic valuation approaches may help in restoration scaling or in damage determination.