Highly variable and synchronised production of seeds by plant populations, known as masting, is implicated in many important ecological processes, but how it arises remains poorly understood. The lack of experimental studies prevents underlying mechanisms from being explicitly tested, and thereby precludes meaningful predictions on the consequences of changing environments for plant reproductive patterns and global vegetation dynamics. Here we review the most relevant proximate drivers of masting and outline a research agenda that takes the biology of masting from a largely observational field of ecology to one rooted in mechanistic understanding. We divide the experimental framework into three main processes: resource dynamics, pollen limitation and genetic and hormonal regulation, and illustrate how specific predictions about proximate mechanisms can be tested, highlighting the few successful experiments as examples. We envision that the experiments we outline will deliver new insights into how and why masting patterns might respond to a changing environment. We review the most relevant proximate drivers of masting and outline a research agenda that takes the biology of masting from a largely observational field of ecology to one rooted in mechanistic understanding. We divide the experimental framework into three main processes: resource dynamics, pollen limitation, and genetic and hormonal regulation, and illustrate how specific predictions about proximate mechanisms can be tested, highlighting the few successful experiments as examples. Masting, or mast seeding, the highly variable and synchronised seed production by plant populations Kelly , is a wiet al. et al. et al. et al. et al. et al. On a proximate level, masting emerges by combining two processes: annual variability in seed production and synchronisation among individuals , while in fertilized stands where N limitation was removed, seed production was affected mainly by temperature during flower primordia development. Analogous results were obtained by Miyazaki et al.  or in space would test the strength of pollen coupling, which predicts that the positive effect of pollen addition on seed set should be negatively related to the density of flowering plants. The phenological synchrony hypothesis can be examined by combining pollen additions with monitoring of flowering times, the prediction being that the effect of pollen addition should be stronger in individuals whose phenology is less synchronized with other plants in the population.A. scaphoides and found increased seed set in years when a low proportion of the population flowered, but no effect in years when the density of flowering plants was high. This result confirmed the density‐dependence of pollination success in this insect‐pollinated species. Pearse et al. (Quercus lobata), but without explicitly exploring whether pollination success was determined by pollen coupling or phenological synchrony. They found increased seed set in one of two years, suggesting that interannual variability in pollen limitation synchronizes seed set consistent with models of mast seeding. Their study also demonstrated that most female flowers were aborted due to factors other than a lack of pollination, leaving considerable remaining uncertainty about the proximate mechanisms involved in masting in this species.There have been few attempts to manipulate pollen levels experimentally, at least in the wind‐pollinated species that disproportionately exhibit masting. In the case of phenological synchrony, no experimental test has been conducted. Similarly, pollen coupling has been tested only in one system. Crone & Lesica  added poe et al.  also addA complication of pollen addition experiments is that fruit maturation can be limited by a scarcity of both pollen and resources. Thus, when resources are limiting, supplementing pollen will not result in greater flower‐to‐fruit transitions. Future experimental attempts should try to discriminate these two factors by crossing pollen addition experiments with resource monitoring or supplementation.Weather can further complicate experimental tests of pollen limitation by influencing flowering. Manipulating among‐plant variation in microclimatic conditions by applying different levels of shading and/or warming can help determine whether microclimatic heterogeneity or the interactive effects of photoperiod and temperature drive flowering synchrony. For example, warm temperatures under short‐day conditions should desynchronize flowering under the photoperiod sensitivity hypothesis, while daylength should be unimportant under the microclimatic hypothesis. Similar setups can be used to test whether higher air temperature around a plant enhances aerial pollen concentrations. No experimental tests of weather variation on pollen limitation have thus far been conducted.et al. To the extent that masting is driven by resources and pollen, plants must have mechanisms to sense their environment and control investment in reproduction as a function of that environment. These mechanisms map onto genetic and hormonal apparatuses that control seed set and are central to understanding the basis of masting  is a heritable trait, whereby offspring respond similarly to the environment as their parents , which increased flowering in some, but not all, years  to snow tussocks , LEAFY (LFY) and APETALA1 (AP1) for five years in Fagus crenata. FT moves from leaves to shoot meristems where it acts to induce flowering, while LFY and AP1 have been identified as necessary for the determination of the floral meristem identity in A. thaliana (Mandel & Yanofsky Fagus crenata that were associated with a variable flowering and fruiting pattern. Crucially, nitrogen fertilization experiments identified N as a key regulator for the floral transition in this species (Miyazaki et al. Examining the molecular basis of environmental cues, such as weather, and testing whether it is resource‐dependent would be a valuable area of future experimentation. A groundbreaking study employing gene expression profiling techniques was that of Miyazaki et al. , who monet al. et al. Astralagus scaphoides (Crone et al. et al. Despite the crucial role of mast seeding in plant regeneration and many other ecological processes (Ostfeld & Keesing et al. et al. We have summarized potential tests of the mechanisms involved in synchronous and intermittent reproduction Table , therebyAll authors conceived the idea and formulated the basis of the experimental framework. MB and AT led the writing of the manuscript, and all authors provided critical feedback and helped shape the final text.


Kidney stone disease should be viewed as a systemic disorder, associated with or predictive of hypertension, insulin resistance, chronic kidney disease and cardiovascular damage. Dietary and lifestyle changes represent an important strategy for the prevention of kidney stone recurrences and cardiovascular damage. A full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, yet it is rarely performed outside of stone specialist clinics. Many patients have a history of kidney stone disease while lacking a satisfactory metabolic profile. Nonetheless, in a real-world clinical practice a rational management of kidney stone patients is still possible. Different scenarios, with different types of dietary approaches based on diagnosis accuracy level can be envisaged. The aim of this review is to give patient-tailored dietary suggestions whatever the level of clinical and biochemistry evaluation. This can help to deliver a useful recommendation, while avoiding excessive dietary restrictions especially when they are not based on a specific diagnosis, and therefore potentially useless or even harmful. We focused our attention on calcium stones and the different scenarios we may find in the daily clinical practice, including the case of patients who reported renal colic episodes and/or passed stones with no information on stone composition, urinary risk factors or metabolic cardiovascular risk factors; or the case of patients with partial and incomplete information; or the case of patients with full information on stone composition, urinary risk factors and metabolic cardiovascular profile.  Kidney stone disease is quite prevalent in western countries: in the United States, its prevalence in a representative sample of the general population reaches 9%  and simiA history of kidney stones is also associated with a higher prevalence of chronic kidney disease and cardiovascular damage or events when compared with non–stone formers ,6,7,8. IThe association between kidney stones and metabolic syndrome and/or cardiovascular disease should prompt physicians to consider the assessment of the cardiovascular risk factors in any adult with kidney stones. The final goal should be an early prevention of cardiovascular, bone and kidney damage ,11 otherKidney stone disease should be viewed as a systemic disorder ,13, assoDietary and lifestyle changes are a major strategy for the prevention of kidney stone recurrences. It is noteworthy that several risk factors for kidney stone formation as well as for cardiovascular damage are modifiable and related to lifestyle and dietary habits .Dietary intervention  aims to Increasing body mass index (BMI) was associated with increasing urine sodium and decreasing pH in men and increasing urine uric acid, sodium, and decreasing urine citrate in women . SimilarLooking at the existing literature in the field of nutritional management for kidney stone patients, several papers and guidelines propose schematic dietary suggestions related to urine abnormalities while others report the effects of nutrients and food categories on different urinary risk factors ,19,20. TBased on their clinical feature and risk of recurrence, kidney stone patients should undergo basic evaluation , or a full metabolic assessment  . UnfortuSo, based on the observed clinical practice experience, in this paper we try to reproduce what may happen in the clinical practice and suggest a pragmatic dietary approach to kidney stone patients in three possible scenarios .A precise diagnosis of stone composition and of urinary risk factors is the basis for a successful treatment and prevention: this should be done for all the kidney stone patients. Namely, analysis of stone composition preferably by infrared spectroscopy and metabolic evaluation, including blood biochemistry and a 24-h urine collection for urinary excretion of calcium, oxalate, citrate, sodium, magnesium, and creatinine should be the gold standard for a kidney stone former assessment ,22. AlthUnfortunately, this rarely occurs in the daily clinical practice. Lack of information and feasibility, costs, poor motivation of physician and patients, are only some of the barriers to the implementation of full metabolic screening for kidney stone disease. Wertheim et al.  reportedWhen an accurate diagnosis, including assessment of 24-h urine solute excretions, is not available or possible, physician and dietician must limit the dietary advice to non-specific suggestions, i.e., increase fluid intake and have a healthy diet while avoiding all misconceptions existing amongst the general population, health professionals and physicians about dietary management of stones. For example, reducing calcium in the diet without a diagnosis of diet-dependent hypercalciuria can induce osteopenia and increase oxalate absorption leading to a high (rather than reduced) risk of calcium-oxalate stone formation. Similarly, reduction of dietary oxalate without a diagnosis of enteric hyperoxaluria may reduce the intake of many vegetables leading to lower alkaline load and fiber intake; in turn this has negative effects on stone formation  and on many cardiovascular (CV) risk factors (increasing of blood pressure and serum lipids). Consensus exists that the first line for the non-specific prevention of kidney stones is a high fluid (water) intake, provided the exclusion of urinary tract obstruction. Low hydration is a risk factor for all type of stones, whereas ensuring a urine volume of at least two liters per day reduces the risk of urine oversaturation. To obtain this goal, fluid intake may vary in function of the extrarenal loss of water as that of the sweating, breathing and perspiratio insensibilis etc., so the daily fluid intake may vary from 1.5 to 3 L. The Guideline of the American College of Physicians  as regarWater mineral composition may represent a modifiable factor for preventing stone formation but an adequate volume is the main goal. The exact daily amount of fluids needed by stone formers is not clearly defined. The most proper suggestion for our patients should not be how much fluids to introduce but how much the urine volume should be, and educate them to measure periodically (for example at the change of season). The prescription of drinking in order to form at least 30 mL/kg of body weight of urine per day may be recommended , which mI cannot drink all this water! May I drink something else? The important thing is that it is a fluid, correct?” A recent study investigated the effect of different beverages on the risk of kidney stones. Higher consumption of sugar-sweetened soda, in particular those containing fructose, was associated with a higher incidence of kidney stones [It can happen that people ask: “y stones . Fructosy stones  and to iy stones ,32. A hiShuster et al.  showed tMoreover, mono and disaccharides intake with these beverages also has a negative impact on the glyco-metabolic profile and weight control, thus increasing the risk of metabolic disorders that in turn may predispose one to stone formation. Coffee and tea were associated with a decreased risk of stones in the Channing cohorts  possiblyAlcohol, and beer in particular, seems to have a protective effect probably because it inhibits antidiuretic hormone secretion, decreasing urinary salt oversaturation . DrinkinWhen and how to drink?” The intake should be distributed appropriately throughout the day, in particular in the most critical periods as after a meal, during the night, in the event of sweating  or gastrointestinal losses (diarrhea or vomiting) [“omiting) .Which kind of water?” Rodgers found that mineral water containing calcium and magnesium should be considered as a possible therapeutic or preventive measure in calcium oxalate kidney stone disease [“ disease . Not all fluids have beneficial effect in reducing the risk of kidney stones . For insA limitation is that citrate content in juice and beverages is not available from nutrients composition tables. In any case, as already mentioned, attention should be paid to the consumption of high amount of citrus or non-citrus and sweetened beverages because of the simple sugar fructose content and the extra-energy supply that may predispose to unfavorable outcomes ,40. In the absence of a known CV and/or kidney stone risk profile guidelines for proper nutrition should be suggested. The key aspects are 1. reducing simple sugars intake while preferring complex carbohydrates; 2. reducing saturated fats while preferring vegetable, mono and poly-unsaturated fats; 3. reducing the use of salted and packaged and preserved foods preferring the fresh ones; 4. increasing the consumption of fruit, vegetables and food rich in fiber; 5. reducing animal protein intake while preferring vegetable sources; 6. maintaining or gaining an ideal body weight and having an active lifestyle.DASH  and Mediterranean diets represent healthy dietary patterns applicable to the general population: they have an additional favorable role in the prevention of kidney stones formation as reviewed by Borghi et al. . Taylor (1) Reduce simple sugars intake while preferring complex carbohydrates: An acute load of glucose causes an increase of calcium urinary excretion in normal subjects which is greater in calcium stone formers. Furthermore, diets with different content of carbohydrates at equal supply of other nutrients causes an increase in calcium excretion directly proportional to carbohydrates intake . A good The association between insulin resistance and uric acid stones disease can be explained by a defect in urine acidification, namely to an impaired L-glutamine system and reduction of Na+-K+ transport at the proximal tubule . This ch2 (PGE2), above all, causes hypercalciuria in a number of ways: it increases intestinal calcium absorption; it decreases its reabsorption in the renal tubules; and it increases bone resorption [(2) Reduce saturated fats while preferring vegetable, mono and poly-unsaturated fats. Stone formers have a high prevalence of hypercholesterolemia and the amount of fat introduced is directly proportional to oxalate excretion. Arachinodic acid in particular seems to be implicated in stone formation. Arachidonic acid is the precursor of prostaglandins. Prostaglandin Esorption . Yasui et al., observed a significant decrease in urinary calcium and oxalate and an increase of urinary citrate after the administration of 1200 mg of fish oil per day .However, the effect of omega 3 intake and supplementation on the lithogenic risk for recurrent nephrolithiasis seem all in all limited .(3) Reduce the amount of salt and preserved foods. High salt intake is associated with an increase of urine calcium excretion. It has been estimated that an increase of 100 mmol of sodium chloride  increases urinary calcium of 1mmol in normal subjects and a two-fold increase in hypercalciuric stone formers. These results come both from salt-loading studies and intake studies on the general population. Nouvenne et al. carried out a randomized controlled trial on calcium stone formers for a period of three months and found that a low-salt dietary regimen corrected idiopathic hypercalciuria in 30% of the cases and seemed to have a positive effect also on other urinary stone risk factors . MoreoveThere is a worldwide effort to carry out policies for salt intake reduction in the general population. However, all previous observations suggested a reduction in excessive salt consumption in stone formers too. In Europe and North America over 75% of salt comes from processed foods or foods prepared in restaurants, 10–12% is naturally present in food and the remaining is added in the kitchen or at the table. The amount of salt recommended by the dietary guidelines is 5–6 g per day. This goal can be achieved with a few simple steps such as to reduce or avoid adding salt at the table, to get used to a taste different from that of salt by using spices, avoiding the consumption of foods containing salt as a preservative, pre-cooked meals and packaged foods.(4) Increase the consumption of fruit, vegetables and food rich in fiber.A higher fruit and vegetable intake is associated with lower risk of urinary stones . SimilarSorensen et al.  too founThe mechanism of the protective effect on the stone risk of a diet rich in fruits, vegetables and fibers is multifaceted. A higher intake of fruit and vegetables may result in a higher urinary oxalate excretion and a greater risk for calcium oxalate nephrolithiasis because of their high oxalate content. However, consumption of fruits and vegetables even more strongly increases urinary citrate, an important inhibitor of lithogenesis thus counteracting the dismal effect on oxaluria. Fruits and vegetables, are also an important source of water, magnesium and potassium, and represent an alkali load that further increases the urinary excretion of citrate . The alkFruit and vegetables together with other food groups rich in fibers such as cereals and legumes have a high content of phytate which is thought to have a protective effect against stone formation. Curhan et al. found an association between higher dietary intake of phytate and lower risk of stones in a cohort of women taking part in the Nurses Health Study II . In the gastrointestinal tract phytate forms insoluble complex with calcium favoring oxalate intestinal absorption . Despite(5) Reduce animal protein intake while preferring plant-derived proteins Animal proteins are rich in purines, sulfur amino acids, oxalate precursors. Moreover, food containing animal proteins are also rich in phosphorus. A high animal protein intake causes renal hyperfiltration, increases urinary uric acid, calcium, oxalate, phosphate excretion, reduces urinary pH and citrate excretion: as a consequence, the overall risk of kidney stones formation rises . UricosuA diet based on vegetable proteins have different effects on lithogenesis. In normal subjects a flesh based diet increases the risk for uric acid stones as compared to a vegetable-based protein diet with the same protein and electrolytes content . This is(6) Maintain or gain an ideal body weight and have an active lifestyle.Both obesity and high energy intake increase the risk of stone formation and incident stones . InconsiIt is noteworthy that kidney stone disease is associated with CV morbidities . Whateve(a) Patients who reported renal colic episodes and/or passed stones with no information on stone composition and/or on urinary risk factors and/or on metabolic cardiovascular risk factors.This is the case when no information about the stone composition and the urinary risk factors is available. In this case, one can only promote a healthy diet and high fluid intake, and regular physical activity .Box 1Practical suggestionsHealthy dietPhysical activityFluid therapyBriefly, reduction of the intake of simple sugars and animal fats while preferring complex carbohydrates and vegetable fats, limitation of salt intake and conserved foods, preferring vegetables-derived proteins instead of animal proteins, increasing the intake of fruits, vegetables and foods rich in fibers. These tips are the main rules for a healthy diet and have been shown to exert a favorable effect on the lithogenic and CV risk. Physical activity is part of a healthy lifestyle; it helps to maintain or gain an ideal body weight. Good hydration is another mandatory recommendation. It is important to explain to the patient that the goal of good hydration is a urinary volume of 2 or more liters per day to avoid super-saturation. Even if specific information is not available a patient-centered approach is preferable; this means to start from patient’s habits and needs and suggest gradual changes to favor adherence to prescriptions. A Decalogue summarizes the proposed non-specific pragmatic approach to kidney stone patients . (b) Patients who formed/passed stones with only incomplete information on stone composition  or on urinary risk factors or on metabolic cardiovascular risk factors.This is the case when we have only partial information, more often including the presence or not of calcium at plain Rx film, or the measurement of 24-h urine calcium or uric acid. Recommendations described in point (a) at the aim of changing patient lifestyle in order to ameliorate dietary habits, increase regular physical activity, achieve better weight control and reduce cardiovascular risk factors should be applied. On top of this, further specific instructions can be added according to available data, generally 24-h urinary calcium and/or uric acid data .Box 2Healthy diet associated to physical activityFluid therapyPractical suggestionslow salt (5–6 g/day) and normal protein (0.8 g/kg body weight) intake, with the preference of proteins from plant origin, namely legumes and cereals. These suggestions are included in the healthy diet recommendationsEnsure an adequate calcium intake (1000–1200 mg/day)Plus, in the case of HypercalciuriaReduce foods with high purine content Limit fats intake Limit fructose intake, especially processed foods Avoid alcohol intakeNormal protein intake, with the preference of protein from plant origin, namely legumes and cerealsHyperuricosuriaIf hypercalciuria is observed, dietary indications include reduction of salt intake and normalization of protein intake. In hypercalciuric stone formers with a normo-calcic diet (about 1g/day), decreasing salt intake reduced calcium excretion . Thus, aIf hyperuricosuria is detected, reduction in purine-rich foods and in animal protein intake lowers uric acid excretion. Greater effects were found if the reduction in purine intake was associated with a healthy diet . Foods rThe suggestion of a healthy diet is also useful because it entails the reduction of animal fat intake and potentially decreases ketogenesis. The hydroxybutyric and acetoacetic acids in particular compete with uric acid at tubular level, and being stronger acids than uric acid, are more easily eliminated by the kidney causing an increase of uric acid serum levels but a lowering urine pH which can favor the precipitation of the uric acid in the urine .A high fructose intake promotes uric acid synthesis. Cell fructose uptake uses ATP very rapidly. Fructose induces nucleotide turnover: an excessive intake of this monosaccharide decreases intracellular phosphate and stimulates uric acid generation. Since fruit is rich in fructose, in case of hyperuricosuria it is proper to suggest avoiding an excess of fruit intake (no more than 2–3 servings per day). Special attention must be paid to processed foods with fructose such as beverages, home-made fruit juice and baby food and to the use of fructose as sweetener. Industrial fruit juice generally has a lower content of fruit (<60%) and fructose (obviously if it is not added as sweetener).+ to NADH subtracting it from glyceradeide-3-phosphate dehydrogenase, thus slowing down glycolysis. The alternative way for energy production is fatty acids oxidation which, in these conditions, leads to ketone bodies production with the previously described consequences.Reducing alcohol consumption may also have positive effects. The ethyl alcohol is oxidized to acetaldehyde in the liver with reduction of NADTo avoid uric acid crystal formation in urine it is important to obtain an alkalizing environment. This can be obtained with the dietary tips previously described: reduction of animal protein preferring protein from plant origin ; increase in vegetables food (but not overdoing with fruits to limit fructose intake). (c) Patients who formed/ passed calcium stones and with full information about stone composition, urinary risk factors and metabolic cardiovascular profile.In the case when a full metabolic assessment is available, we can give targeted information to the patient. It is important to remember that the following instructions must be considered in addition to a healthy diet and a proper fluid therapy .Box 3Practical suggestionsHealthy diet associated to physical activityFluid therapyIf hypercalciuria is diet-dependent a low calcium intake (400 mg/day) is recommendedIf hypercalciuria is not diet dependent, a calcium intake restriction is not recommended and an adequate calcium intake (1000–1200 mg/day) should be ensuredlow salt (5–6 g/day) and normal protein (0.8 g/kg body weight) intake, with the preference for proteins of plant origin, namely legumes plus cereals. These suggestions are included in the healthy diet recommendationsPlus, in the case of HypercalciuriaAvoid foods with a high content of oxalate Do not avoid fruit and vegetablesEnsure an adequate calcium intake (1000–1200 mg/day)Avoid excessive intake (>500 g/day) of ascorbic acid (Vitamin C), vitamin C supplements in particularHyperoxaluriaIn addition to proper fluids therapy and healthy dietIncreased fruit and vegetablesModerate intake of citrus based beverage paying attention to simple sugar and energy intakeHypocitraturiaIn this case, dietary calcium restriction is only appropriate in the case of diet-dependent hypercalciuria. A low calcium diet (440 mg/24-h) in calcium stone formers decreased calciuria but increased the urine oversaturation of calcium-oxalate in hypercalciuric patients . In hypeOther recommendations to reduce hypercalciuria have already been described. Oxalate is the final product of glyoxylate oxidation, an intermediate of glycine metabolism and is abundantly present in vegetables. In normal conditions the amount of oxalate from endogenous metabolism and from the diet is low and daily oxaluria ranges from 15 to 30 mg. Approximately 50% comes from the diet. Its solubility depends on urinary pH and the presence of calcium ions and it is generally completely dissociated in the urine. Increased excretion of urinary calcium can cause calcium-oxalate crystals formation. The intestinal absorption of oxalate depends on the availability of free calcium in the intestinal lumen. If this is reduced  oxalate can be easily absorbed . On the An important suggestion to give to stone patients is that oxalate rich food assumption should go together with calcium containing foods. In particular, they should be warned that some energetic nutritional supplements taken during or after physical performances are very rich in oxalate  and poor in calcium. These power bars can induce the over-excretion of oxalate when urine volume is low because of the exercise induced sweating, thus favoring calcium-oxalate crystallization.Ascorbic acid degradation results in oxalate formation. The breakdown of 60 mg of ascorbic acid to oxalate potentially results in the formation of up to 30 mg oxalate per day. Taylor et al.  has founTaylor et al.  and ThomThe hypothesis was advanced that it is possible to modulate gut oxalate degradation by the intestinal microbiota. However, in a study using supplementations of the probiotic lactobacillus no reduction in oxalate urinary excretion was observed . FurtherHypocitraturia is a common metabolic alteration in kidney-stone formers. Renal excretion of citrate is strictly linked to acid-base status. The acid-base balance is regulated by the net endogenous acid production in relation to acidifying and alkalizing foods and by organic acids metabolism. Fruits and vegetables are the main source of dietary alkalinizing compounds while foods rich in animal proteins such as meat, poultry, fish, eggs, have an acidifying effects due to the presence of sulfuric amino-acids. Hypocitraturic patients generally have a low intake of vegetables. A high intake of fruit and vegetables , increased citrate excretion and reduced urinary saturation for calcium oxalate and calcium phosphate ,78. As rA full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, but it is quite rarely performed outside of specialized stone clinics. Many patients who have a history of kidney stone disease do not undergo a complete metabolic profiling. However, in this real-world clinical practice, it is still possible to rationally manage kidney stone patients. Different scenarios, with different types of dietary approaches, on the basis of the diagnosis accuracy level can be envisaged . In this review we gave dietary suggestions tailored to individual patients whatever his/her level of clinical and biochemistry evaluation. This approach can help to deliver useful recommendations, avoiding excessive dietary restrictions that may not be based on a diagnostic assessment, and which therefore may be potentially useless or even harmful.


Understanding diversity in flower-visitor assemblages helps us improve pollination of crops and support better biodiversity conservation outcomes. Much recent research has focused on drivers of crop-visitor diversity operating over spatial scales from fields to landscapes, such as pesticide and habitat management, while drivers operating over larger scales of continents and biogeographic realms are virtually unknown. Flower and visitor traits influence attraction of pollinators to flowers, and evolve in the context of associations that can be ancient or recent. Plants that have been adopted into agriculture have been moved widely around the world and thereby exposed to new flower visitors. Remarkably little is known of the consequence of these historical patterns for present-day crop-visiting bee diversity. We analyse data from 317 studies of 27 crops worldwide and find that crops are visited by fewer bee genera outside their region of origin and outside their family's region of origin. Thus, recent human history and the deeper evolutionary history of crops and bees appear to be important determinants of flower-visitor diversity at large scales that constrain the levels of visitor diversity that can be influenced by field- and landscape-scale interventions. Baker ,8 inferr success .While pollinator-dependent crops yield valuable harvests even when cultivated away from their region of origin, some lines of evidence indicate that flower-visitor diversity influences agricultural outcomes nevertheless. Global reviews suggest that pollen limitation of fruit set is surprisingly frequent in crops , and thaFurther to consequences for crop production, it is important to understand drivers of crop-visiting bee diversity in terms of the biodiversity conservation value of agricultural landscapes. Exotic plants have been shown to attract fewer pollinator taxa compared to native plants in one north American study . If thisWhile the field-scale drivers of crop-visitor diversity, such as pesticide and habitat management, are reasonably well understood ,18, driv(a)Geographical variation in crop-visitor diversity might arise from the biogeographic history of each crop species and the opportunities for plant and bee adaptation this entails. A parallel can be found in the enemy release hypothesis, which states that exotic species escape specialist enemies that have adapted to them in their native range . Consist(b)Peponapis  and Diadasia  that readily visit introduced Old World crops as long as they come from their preferred host families [The deeper biogeographic histories of crop lineages might give rise to another level of geographical variation in crop-visitor diversity, in which the presence of confamilial species influences pollinator availability. This idea is similar to the observation that specialist natural enemies native to the invaded range can be pre-adapted to exotic plants through adaptation to the native relatives of these plants in the invaded range . Similarfamilies ,27. The families  presumab(c)If crops are visited by more bee taxa in their and their family's realm of origin (predictions 1 and 2), one might expect the suite of native crops grown in a region to collectively support more bee taxa than are supported by the suite of exotic crops . This may not be the case, however, if the crops native to a particular region are dominated by species that support fewer bees in general , despite supporting more bees in their native compared to introduced ranges. Since we argue that crops will typically exhibit generalized pollination systems, we predict that suites of native crops will support more bee taxa than suites of exotic crops grown in each region.2.(a)To test these predictions, we analysed observations of flower-visiting bees for 27 crop species in six families  . Each plHaving selected a candidate list of plant families, we conducted a literature review of bee visitation to the crop species in each family using Web of Science, CAB Abstracts and Google Scholar (first 100 hits only) with the following search terms: (genus AND species AND visit*) OR (genus AND species AND pollinat*), where genus and species included all synonyms for each crop. These searches returned over 10 000 articles, so a hierarchy of filters was applied to focus on the most relevant studies. The first filter was applied to titles of papers to remove obviously irrelevant material (e.g. studies comparing effectiveness of different crop varieties as pollinizers). A second filter applied to title and abstract for relevance (e.g. any mention of flower visitors or pollinators). A third filter was applied to ensure appropriate taxonomic resolution of flower-visiting bees, selecting those studies that identified all bees visiting crops to at least genus level. Where these data were not included in the published article but it seemed likely the data had been collected, we contacted authors and requested these data. Two studies on small, isolated islands were excluded due to possible island biogeography effects.https://www.itis.gov) and recent literature (any taxonomic revisions obtained from the first 10 hits on Google Scholar using the following search terms: genus AND taxonom*) when ITIS record reviews were greater than 5 years old.We chose bee genus, rather than species, to reduce the risk of error in species identification and because genus reflects a deeper level of trait diversity among bees. Between-study differences in the number of bee genera reported could result from the fact that different studies were conducted in different decades encompassing different understandings of bee taxonomy, so genus names were compared to the online Integrated Taxonomic Information System number and identity of bee genera observed visiting each crop,(2)biogeographic realm and latitude of location(s) where crop visitors were observed (centroid of locations when there were multiple within a study),(3)number of locations where crop visitors were observed.The following data were then extracted from each study:We recorded the numbers of locations observed in each study because the number of bee taxa recorded visiting any crop is likely to increase with the number of locations surveyed, particularly where surveys occur across gradients of land cover. We noted the latitude of the location (or the centroid where there were multiple locations) to account for underlying latitudinal gradients in species richness . We used(b)The biogeographic histories of crop species and plant families were determined on the basis of a literature search using Google Scholar with the following search terms: (genus AND species AND orig*) OR (genus AND species AND domesticat*), and (family AND orig*) or (family AND evolution). We attempted to attribute a single origin to each crop and family according to the most recent published studies, though some crops and families were given multiple origins in cases where origins are currently controversial or there were multiple, independent domestications in different biogeographic realms . The descriptions are the most current found for family and crop origin based on best available data. Box 1. Cucurbitaceae crops are used to illustrate the history of plant movement in three time periods: pre-human (greater than 10 000 years before present (ybp), red arrows), human-mediated pre-Columbian  and human-mediated post-Columbian . Note that for the earliest dates, the position of continents were different. The Cucurbitaceae family originated 70 million ybp in the area we now call Indomalaya, spread first to the Afrotropics and Neotropics and then to Palaearctic Europe and the Nearctic [Nearctic .Cucumis melo and C. sativus first appeared in the Palaearctic 5000 ybp and 2000 ybp, respectively [Citrullus lanatas originated in sub-Saharan Africa around 3 million ybp [Cucurbita pepo was domesticated twice independently, once along the Neotropic–Nearctic border around 10 000 ybp, and again further north in the Nearctic around 5000 ybp [Cucurbita moschata was domesticated in the northern Neotropics around 10 000 ybp and C. maxima in the southern Neotropics sometime after [Cucurbita remains have not typically been identified to species. All species attained global distributions following the arrival of Europeans in the Americas around 500 ybp.Cultivated ectively , althougectively . Citrulllion ybp , and waslion ybp . It sprelion ybp . Cucurbi5000 ybp . Cucurbime after ,40. Therme after , though (c)To provide insight into between-realm differences in overall richness of genera and differences in the amount of data available in our dataset, we provide accumulation curves for the number of bee genera observed in each realm  using thOur first two predictions—that crops will be visited by more bee taxa in their realm of origin and family origin—were tested using regression models with each crop in each study treated as an observation. We modelled the number of bee genera visiting the crop as a function of the terms described in electronic supplementary material, table S1, with crop origin and family origin representing our first two hypotheses, and all other terms used to account for additional sources of variation in bee genus richness.We used mixed-effects models with crop species as a random effect to account for possible intrinsic differences between crops with more or less generalized pollination systems. Poisson models were over-dispersed, so negative binomial models were used, with a quadratic rather than linear mean–variance relationship specified as it provided a better fit to the data. Generalized variance inflation factors were calculated for the global model  and were all less than 1.9, suggesting that multicollinearity was not at a level that would complicate interpretation.We used an information theoretic approach to model selection. We first used AICc to compare the global model with linear and quadratic functions of latitude as there is some evidence of a hump-shaped relationship between bee richness and latitude , but we Thirty studies described visitors to more than one of the focal crops, which introduces some risk of non-independence. However, when we performed the analysis after removing studies with multiple crops, the model selection outcomes were unchanged, and parameter estimates and confidence intervals changed only slightly, so we present the analysis of data from all studies.Our third prediction—that suites of crops native to a region collectively support more bee taxa compared to exotic crops—was evaluated by comparing bee genus accumulation curves for native crops and exotic crops within each biogeographic realm. The identity of each bee genus recorded visiting each crop across all studies within each biogeographic realm was used to produce crop species–bee genus interaction networks (i.e. presence/absence of each crop species–bee genus interaction) for each biogeographic realm. These networks were then used to produce for each realm two accumulation curves  for the number of bee genera observed in the network as crop species were added, one curve with ‘native’ crops as samples and one with ‘exotic’ crops as samples. We defined ‘native’ crops as those originating in or belonging to families originating in the focal realm, and ‘exotic’ crops being those originating in and belonging to families originating in other realms. Accumulation curves were used to determine whether the number of bee genera entering each network increased more rapidly with the addition of native compared to exotic crops to the network, such that agricultural regions with a greater diversity of native compared to exotic crops would be expected to support more bee genera. The sample-based rarefaction method ‘exact’ in R package ‘vegan’  was used3.(a)Our literature search produced a database of 317 articles  describing bee genera visiting 27 crop species across 1520 locations in five biogeographic realms figures . The numApis, Ceratina, Eucera and Xylocopa from the Apidae family, Halictus and Lasioglossum , Colletes (Colletidae) and Megachile (Megachilidae) . Most of these genera were detected visiting crops from most families in all realms , whereas Eucera and Colletes were detected visiting crops from only one or two families in most realms (data not shown). Eighty-seven bee genera were observed visiting crops in only one realm , and most of these were detecting visiting crops from only one or two families (data not shown).Forty-five bee genera were detected visiting crops in all biogeographic realms, including Genus accumulation curves for each biogeographic realm revealed between-realm differences in overall richness of bee genera, and differences in the amount of data available . Bee gen(b)R2 for generalized linear models), which equalled 49%.Our first two predictions were supported by results of regression analyses, with geographical variation in crop-visitor diversity explained by the biogeographic histories at the level of crop and also crop family. The top-ranked regression models explaining variation in the number of crop-visiting bee genera contained crop origin and family origin, as well as biogeographic realm, latitude and number of locations . The top three models encompassed greater than 95% of the Akaike weight and all contained crop origin, biogeographic realm and number of locations, though only two contained family origin and latitude, indicating these two variables were less important . According to the best model, which was substantially better than all other models (ΔAIC > 2), 95% confidence intervals excluded one for all parameter estimates . There iIn agreement with our first prediction, crops were visited by more bee genera in their biogeographic realm of origin compared to other realms. The average number of bee genera visiting crops across all studies of a single location in their regions of origin was 4.5. Crops grown outside their realm of origin attracted 1.3, or approximately 27%, fewer genera on average . The secn = 9) and Old World (n = 11). This shows that effects are reciprocal.To demonstrate that the effect of crop origin is reciprocal, i.e. that the same patterns apply for introductions from New to Old World and Old to New world, we produced electronic supplementary material, figure S3 using the best regression model (above) but with crop species treated as a fixed effect, and an interaction between crop and crop origin. Twenty of the 27 crops (74%) showed some indication of greater crop-visitor diversity when grown in the region of origin, with similar numbers of these crops originating in the New World , increased with the number of sites, and was higher in the Nearctic and Neotropic compared to all other realms .(c)Our third prediction found mixed support from genus accumulation curves. Since regression modelling found positive, additive effects of crop origin and family origin on crop-visiting bee genera, we compared bee genus accumulation curves for both native  and exotic crops. In the predominantly tropical realms , bee genera accumulated in networks more rapidly for native compared to exotic crops . In othe4.Recently observed declines of insect pollinators ,46 have Our findings suggest that present-day global variation in crop-visitor diversity arises from the particular biogeographic history of each crop. Crop species tended to attract more bee genera in their realm of origin, where there has been more time for adaptation to occur. Most crop introductions to biogeographic realms outside regions of origin have occurred in the last 500 years, during exchanges of organisms between the New and Old World realms following the arrival of Europeans in the Americas. While some phytophagous insects have adapted to plants introduced during this time , our resWe also found that crops attracted more bee genera in the realm of their family's origin. This suggests some level of pre-adaptation to exotic relatives of native mutualistic partners, which is consistent with observations of highly specialized bees visiting exotic plants belonging to their native host families . HoweverKnowledge of crop biogeographic history can be used to refine biodiversity conservation strategies in agricultural landscapes. Current practices that are effective in promoting bee diversity in production landscapes are the retention or restoration of non-farm vegetation, reduced pesticide use and increased on-farm floral diversity through wildflower plantings or crop polycultures ,17. Our By contrast, native crops did not collectively support more bee genera compared to exotic crops in the predominantly temperate Nearctic and Palaearctic realms. The native crops of temperate realms might exhibit floral traits tending to support fewer of the bee taxa favoured by agricultural landscapes. All Rosaceae crops are native to the temperate realms and are grown in seasonally cool environments at higher latitudes or altitudes where they typically flower for a short period of time in early spring. While many crops native to the predominantly tropical realms can be grown in the same seasonally cool environments, they typically flower later in spring or summer –52. In tDiadasia and Panurginae genera Acamptopeum, Calliopsis, Callonychiumt, Anthrenoides, Pseudopanurgus, Psaenythia and Perdita; electronic supplementary material, tables S5 and S6). By contrast, stem-nesting  is most frequent in Megachilidae and Xylocopinae which are least diverse in the New World. Further research is required to test the ‘agricultural tolerance’ hypothesis as our literature-based analysis was unable to distinguish biological from non-biological explanations of biogeographic realm effects.More bee genera were recorded visiting crops in the New World (Nearctic and Neotropic) rather than Old World realms, but there are multiple possible contributors to this apparent diversity pattern. There could be a spurious influence from geographical differences in taxonomic practice. This pattern could also be influenced by between-realm differences in cropping systems, since New World realms are dominated by large-scale monocultures whereas most of Asia and Africa is dominated by smallholder farming , though The global-scale drivers revealed in this study indicate that human impacts on crop-visitor diversity have been occurring over thousands of years of inter-continental trade and migration, intensifying after the establishment of trade networks between New and Old World realms, and well before the advent of pesticides and agricultural intensification. Our findings of lower crop-visitor diversity when grown outside crop or family origins parallel observations of plant–enemy interactions ,25. The


In low-resource settings where disease burdens remain high and many health facilities lack essentials such as drugs or commodities, functional equipment, and trained personnel, poor quality of care often results and the impact can be profound. In this paper, we systematically quantify the potential gain of addressing quality of care globally using country-level data about antenatal, childbirth, and postnatal care interventions.n = 17) and sample medians applied as a proxy in countries without linked data. Lastly, these 2016 starting baseline levels were raised to reach targets in 2020 as endline based upon country-specific utilization  from the latest DHS or MICS population-based reports. Our findings indicate that if high-quality health systems could effectively deliver this subset of evidence-based interventions to mothers and their newborns who are already seeking care, there would be an estimated 28% decrease in maternal deaths, 28% decrease in neonatal deaths, and 22% fewer stillbirths compared to a scenario without any change or improvement in quality of care. Totals of 86,000  maternal and 0.67 million  neonatal lives could be saved, and 0.52 million  stillbirths could be prevented across the 81 countries in the calendar year 2020 when adequate quality care is provided at current levels of utilization. Limitations include the paucity of data to individually assess quality of care for each intervention in all LMICs and the necessary assumption that quality of care being provided among the subset of countries with linked datasets is comparable or representative of LMICs overall.In this study, we created deterministic models to project health outcomes if quality of care was addressed in a representative sample of 81 low- and middle-income countries (LMICs). First, available data from health facility surveys  conducted 2007–2016 were linked to household surveys  to estimate baseline coverage for a core subset of 19 maternal and newborn health interventions. Next, models were constructed with the Lives Saved Tool (LiST) using country-specific baseline levels in countries with a linked dataset (Our findings suggest that efforts to close the quality gap would still produce substantial benefits at current levels of access or utilization. With estimated mortality rate declines of 21%–32% on average, gains from this first step would be significant if quality was improved for selected antenatal, intrapartum, and postnatal interventions to benefit pregnant women and newborns seeking care. Interventions provided at or around the time of childbirth are most critical and accounted for 64% of the impact overall estimated in this quality improvement analysis. Victoria Chou and colleagues estimate the implications of poor-quality care for maternal and child health outcomes in low- and middle-income countries. In low- and middle-income countries, health systems struggle to provide high-quality medical care to pregnant women and their newborns in need.Delivery of key health interventions is critical to save lives and prevent morbidity and mortality in high-burden settings.The impact of extant or poor quality of care at a population level is poorly understood, and quantifying the benefits of improving quality among those already seeking or accessing care would be a critical first step for prioritization.To examine the global impact of improvement in the quality of care, we used a linking approach, which combines health facility and population-level survey data to estimate baseline for a subset of important evidence-based interventions.Intervention coverage trends were modeled in 81 countries by setting current levels of reported utilization as the final country-specific targets for 2020.If those seeking medical attention arrived at facilities reimagined with adequate resources and receive high-quality care, our systematic tally indicates that almost one quarter of the maternal deaths, neonatal deaths, and stillbirths would be preventable during the period 2016–2020 if the gaps in quality of care were eliminated.Countries and current health systems are far from ensuring that skilled providers with adequate supplies are providing timely and appropriate healthcare to existing populations in need. Our analysis of potential gains quantifies the consequences of these missed opportunities, ranging from the prenatal to postnatal periods.Bolstering the quality of care is an essential checkpoint because efforts to increase utilization will rely on the same health systems where vulnerable populations are presently accessing care.With greater attention focused on tracking country-level progress, more data will hopefully become available to effectively monitor changes in coverage for key maternal and neonatal interventions. As these parameters or inputs are better defined, modeling can contribute to the body of knowledge by offering an informed approach to examine quality of care gaps so that better strategies can be developed to improve health among mothers and their children seeking care in this context. Achieving targets for the Sustainable Development Goals (SDGs) for 2030 will require not only rapid accelerated change but also robust linkages established across many sectors. The central importance of a high-quality, well-functioning, and resilient healthcare system to deliver proven interventions was championed over a decade ago by the World Health Organization (WHO) , and theHealth systems strengthening and the focus on an integrated approach coincides with increasing awareness that quality of care is a complex, multifactorial, but critical driver that can catalyze progress or mire potential success . The LanWHO’s vision for pregnant women and newborns centers on provision of established life-saving interventions through high-quality and timely care to effectively reduce leading causes of mortality and morbidity worldwide . QualityTo this end, mathematical models have served as a valuable platform, because outcomes can be mapped into the future and measurable gains can be quantified for evaluation or strategic planning purposes . ProjectThe aim of this study is to estimate the global impact of poor quality of care in countries where disease burdens remain high and elevated morbidity and mortality persist. To achieve this aim, we conducted a multicountry analysis with a novel application combining elements from health facility assessments with utilization data to first examine intervention coverage. This insight is then used to estimate impact  if points of contact made with the existing healthcare system during pregnancy and labor were no longer serving as empty placeholders. Our modeling approach explores the global consequences if the quality gap could be closed so that “effective coverage,” or the “fraction of potential health gain that is actually delivered to the population through the health system” , could bThe LiST, a linear and deterministic model , was useCountry-specific models for a sample of 81 low- and middle-income countries (LMICs) representing the majority of the global burden being tracked by Countdown to 2030 were created see , with mon = 17) are shown in Using a linking approach, nationally representative data for the study period from 2007 to 2015 were collated from health facility assessments  and then combined with data from household surveys . Linked surveys were separated by an interval of ±2 years or less, and countries with linked datasets available (n = 19). This subset of 19 life-saving maternal and neonatal health interventions was selected because the availability of key components  was assessed during SPA or SARA data collection and indicators could be constructed for readiness as a proxy for the quality of care. These interventions were drawn from the complete listing of 60+ interventions available in the module , and ownership of insecticide-treated bednets. Our analysis focused on modeling “what if” well-functioning health systems could ensure high-quality care to merely provide a subset of 19 evidence-based maternal and neonatal interventions to those who are currently accessing or utilizing the existing service platforms. Present levels of utilization were found to be low overall, with an average of 60%  of women reportedly attending four or more antenatal visits and 66%  of deliveries occurring in a health facility, based upon national reports. Despite incorporating these low levels of utilization as the modest targets for 2020, we estimated a substantial reduction in the aggregate global sum of maternal deaths (28% decrease), neonatal deaths (28% decrease), and stillbirths (22% decrease) in the final year compared to a scenario without any change or improvement in the quality of care. In our representative sample of 81 high-burden countries, a total of 86,000  maternal, 0.67 million  neonatal lives could be saved and 0.52 million  stillbirths could be prevented in 2020 if populations in LMIC settings maintained the current levels of health system use but the standard for quality of clinical care was raised .Ensuring a minimum threshold of quality for this set of MNCH interventions would also produce declines in estimated mortality rates. On average, maternal mortality ratio (MMR) would drop 32%, neonatal mortality rate would decrease 31%, and the stillbirth rate would drop 21% according to the modeled projections for these 81 countries . For matOf the life-saving interventions that were examined, improvements to close the quality gap for key interventions provided at or around the critical time of childbirth would produce the greatest benefit. Interventions during this period accounted for 64% of the impact overall , which exceeded benefits quantified for the antenatal or postnatal periods.In this study, we created linear and deterministic models to examine the global impact of low-quality or inadequate care in a representative sample of 81 LMICs with recent national-level data. We quantified potential declines in mortality and found that gains would be sizeable if baseline levels of a focused package of life-saving interventions were set to reach higher levels, with effective coverage equivalent to currently reported utilization. Our analysis used a novel linking approach to combine health facility datasets, which provide an assessment of readiness, with household surveys, which report on patterns of utilization around the same time period. This ecological approach is advantageous to estimate baseline coverage for important interventions that cannot be tracked through the standard approach, which relies on participant self-reports in household surveys. This set of country-specific models, which represents a large majority of the global burden, found that scale-up of high-quality care for selected MNCH interventions would be invaluable.n = 81) where most of the maternal and neonatal deaths and stillbirths are occurring. Using a mathematical model, our quantification of the benefits of eliminating poor-quality care is based upon recent country-level data collected with health facility and household surveys. The estimates of health impact presented here focused exclusively on mothers, newborns, and stillbirths as the direct beneficiaries of the life-saving interventions we modeled, and we did not account for any of the broader impact if adverse consequences known to be associated with these fatalities [The strengths of our study are based upon the analysis of a large, population-based, representative sample of countries Click here for additional data file.S1 TableLiST, Lives Saved Tool.(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S1 TextLiST, Lives Saved Tool.(PDF)Click here for additional data file.


A plethora of tools and methods are being used to evaluate alcohol’s effects on cognitive functioning. Neuropsychological tests focus on identifying the brain regions affected by alcohol, whereas neurocognitive approaches attempt to distinguish impaired cognitive processes. These approaches are supplemented by neurophysiological and neuroimaging tools. Studies using all these instruments have characterized alcohol’s effects on cognitive functioning after both acute and chronic alcohol consumption. However, there are limitations to the generalizability of these findings because the subjects in the vast majority of studies do not adequately represent all subgroups of the general population. Chronic alcohol abuse frequently is accompanied by significant impairment in mental abilities , and eveTo illustrate how cognitive functions and cognitive impairment can be assessed, this article reviews some of the methods used to evaluate alcohol’s impact on cognitive performance. These methods include neuropsychological and neurocognitive tests as well as neuroimaging techniques. Although most of these techniques primarily are used to analyze cognitive impairment resulting from chronic alcohol abuse or dependence, the results of studies assessing the cognitive consequences of acute alcohol consumption also are mentioned. The article concludes with a discussion of factors that may limit the general applicability of current research findings, specifically age and gender biases in the choice of study subjects.Much of the work regarding the effects of chronic alcohol consumption on mental processes has focused on identifying specific neuropsychological domains—and the brain regions associated with them—that are affected by alcohol. These empirically determined functional domains describe areas of cognitive or psychological functioning, such as abstract thinking and problem-solving or perceptual-motor skills.In early studies of alcohol’s effects, cognitive test batteries generally evaluated overall intelligence and neuropsychological functioning. Researchers since have refined these tests to assess more specific aspects of intelligence or neuropsychological functioning. An exhaustive review of all the instruments currently in use is beyond the scope of this article. Instead, a selection of these tools is presented in Many of the tests described in In recent years, a new approach adopted from the field of neurocognitive science has been applied to studies of chronic alcohol effects. This approach focuses on the specific processes underlying cognitive functioning . Although the specific performance requirements are similar for both the neurocognitive and the traditional neuropsychological tests, the variables being measured and analyzed are different.For example, in both approaches, subjects may be asked to memorize a story, associate pairs of items, or identify a target. The neuropsychological approach might focus on determining whether skills associated with right hemisphere function  or with left hemisphere function  are impaired after chronic alcohol abuse. In contrast, the neurocognitive approach might assess alcohol’s differential effects on processes such as the perception, encoding , or retrieval of information.specific processes.Because of their different focuses, the two approaches also differ in their clinical significance. For example, the neuropsychological approach can locate an impaired brain region  based on the functional impairment observed. Similarly, neuropsychological tests can identify brain regions and their associated functional domains that have been spared from damage. The neurocognitive approach, on the other hand, by identifying underlying cognitive processes or mechanisms, may help develop treatment strategies attempting to rehabilitate these The increasing interaction of basic neuropsychological research and process-oriented neurocognitive research represents a new phase in the study of alcohol-related cognitive impairment. Some studies incorporate both neuropsychological and neurocognitive techniques. Although this combined approach requires a higher time commitment both for participants and for researchers, it creates an extensive knowledge base regarding brain/behavior relations that may help improve the understanding and treatment of alcohol-induced cognitive dysfunction.The findings regarding cognitive deficits following chronic alcohol abuse vary considerably. However, most neuropsychological studies indicate that detoxified alcoholics frequently demonstrate long-lasting deficits in four domains: abstract thinking and problem-solving skills, verbal skills and/or memory, perceptual-motor skills , and visuospatial skills . A disc.The neuropsychological domains appear to be differentially sensitive to the effects of chronic alcohol consumption. Whereas abstract thinking, perceptual-motor skills, and visuospatial skills almost always are affected by chronic alcohol abuse, alcohol-related deficits in verbal skills appear less frequently . The reaIn addition to performance-based neuropsychological and neurocognitive tests, neuroimaging techniques also are used to assess alcohol-related cognitive impairment. These techniques include electroencephalography (EEG), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT) and computerized tomography (CT).  of the ERP occurring approximately 300 milliseconds after the presentation of a relevant, but rare, stimulus. In a prototypical experiment called the odd-ball paradigm, subjects must attend to a specific infrequent stimulus  while ignoring another more frequently occurring stimulus. For example, subjects observing a series of red and green dots appearing in rapid succession on a computer screen, with the green dots outnumbering the red ones, are asked to count the “rare” red dots. The occurrence of the rare yet relevant red dots among the irrelevant green dots elicits a P300 ERP response.The P300 has been associated with target identification and the memory updating system  . CurrentAlthough the types of tasks used to assess acute alcohol effects often are similar to tasks used to assess chronic alcohol effects, the primary focus of the two types of studies has been different. Specifically, contrary to the studies of long-term alcohol effects on cognition, studies of acute effects have tended to focus on tasks that assess performance of functions relevant to driving and other practical skills. Thus, many of these studies have used an information-processing approach with particular interest in changes in reaction time and response accuracy under various conditions of alcohol exposure.There have been literally thousands of studies conducted on the effects of acute alcohol administration. Several reviews, such as the ones described below, attempt to integrate this vast literature. In addition to summarizing the general findings, these reviews illustrate the broad range of variables and techniques used to assess alcohol’s effects on cognitive functioning.More recently, People experience alcohol’s subjective intoxicating effects at lower BAC’s than alcohol-induced performance impairment.Whereas a linear relationship exists between BAC and performance impairment over a wide range of BAC’s , there appears to be a threshold BAC below which people do not experience subjective intoxication.The effects of alcohol are greater on tasks or processes demanding attention or effort  than on tasks or processes making few attentional demands .Seventy to 80 percent of the studies found that BAC’s at or below 0.04 percent had significant effects on intoxication ratings and on the performance of controlled tasks.Characteristics of the study subjects, such as expectancyRather than consider alcohol’s effects only on specific behavioral tasks, some researchers have suggested that acute alcohol administration has a global effect on cognitive functioning. For example, Although alcohol-related myopia is unlikely to account for alcohol’s effects on behavior in all contexts, other studies support this interpretation. For example, Although numerous studies have analyzed alcohol’s effects on cognitive functioning and performance, their findings may not apply to all members of the population to the same extent. For example, the vast majority of studies include only young, healthy men and thus may not reflect alcohol’s effects on older people or women. This bias in the selection of study subjects may be the result of concerns about undetected pregnancy in women or the lack of appropriate control subjects among older people.Few studies have analyzed gender differences in the consequences of acute alcohol effects on cognitive functioning. Existing data indicate similar patterns of cognitive dysfunction in male and female alcoholics . This is remarkable because female alcoholics consistently report fewer years of drinking and/or a lesser quantity per drinking occasion than male alcoholics (for reviews, see Numerous diagnostic instruments are available to assess alcohol-related changes in cognitive functioning and to detect subtle and specific impairment. Based on the performance of specific tasks, neuropsychological and neurocognitive tests can help identify both the brain structures and the cognitive processes affected by alcohol consumption. These findings may contribute to the development of treatment approaches appropriate for patients with different kinds of cognitive impairment. Furthermore, by revealing information about cognitive impairment, these findings indirectly may stimulate new approaches to the study of the brains of healthy persons. However, to maximize the benefits from these tools, researchers must carefully select the test best suited to answer their specific research question and document how cognitive functioning has been assessed.The testing instruments have been used in many studies and have provided insight into the consequences of chronic and acute alcohol consumption. However, there are limitations to this work. Foremost is the fact that most of the studies have used primarily healthy young men as subjects. Relatively few studies specifically have assessed the neuropsychological, neurocognitive, and neurophysiological consequences of alcohol consumption in other population subgroups. Preliminary findings in older people and women underscore the necessity of expanding this line of research to understand fully alcohol’s effects on cognitive functioning.


Clinicians routinely report not practising evidence-based treatments with eating disorders. There has been limited research investigating the impact of adaptable clinician characteristics such as self-efficacy and therapeutic optimism in this area. This study evaluated if there is a relationship between clinician therapeutic optimism, self-efficacy and the provision of evidence-based practice in the treatment of bulimia nervosa and binge eating disorder.A survey developed for this study was administered to 100 psychologists who were recruited online via a range of organisations affiliated with psychology and/or eating disorders. The survey measured demographic factors, eating disorder treatment knowledge, treatment fidelity, the use of individual treatment components and a range of clinician characteristics including self-efficacy and therapeutic optimism.Results demonstrated that clinician self-efficacy was positively associated with and predicted treatment fidelity. Therapeutic optimism had significant low correlations with treatment fidelity but did not predict treatment fidelity.These findings would suggest that strengthening clinician self-efficacy is useful in improving evidence-based practice in the treatment of binge eating disorder and bulimia nervosa and may also have implications in the training of clinicians. The study also demonstrated that the use of a range of knowledge translation strategies are valuable in enhancing clinician adherence to evidence-based practice. Further research with direct measures of treatment fidelity is needed to clarify these findings.The online version of this article (10.1186/s40337-018-0208-0) contains supplementary material, which is available to authorized users. The best current treatment for bulimia nervosa and binge eating disorder in adults is cognitive behavioural therapy. Despite this, research has shown that many clinicians do not deliver this treatment as intended. There are a range of factors that may impact on why this occurs. In this study, we looked at various clinician characteristics that may impact on the quality of treatment being provided to individuals. It was shown that a clinician’s level of self-efficacy in delivering cognitive behavioural therapy impacted on their ability to implement treatment as planned. This has significant implications in the training of clinicians delivering treatment for adults with eating disorders.Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [real world settings for a variety of eating disorders, including BED and BN [Bulimia Nervosa (BN) and Binge Eating Disorder (BED) are the two major eating disorders found in those that are not underweight, and defined in the fifth edition of the  (DSM-5)  by frequ (DSM-5) , 3. A ra (DSM-5) –6. This  (DSM-5)  guidelin (DSM-5) . EffectiD and BN –11. TherDespite this well-established evidence-base for the efficacy of CBT for BN and BED, a wealth of literature suggests that many psychologists are not delivering treatments as intended (treatment fidelity) and deviating from the protocol over time (therapist drift) –15. ClinWaller, Stringer and Meyer  identifiThis has also been supported by other studies which collected data directly from clients recalling their experiences of treatment for an eating disorder , 21, 22.An alternate explanation could be that clinicians do have the knowledge, but clinician characteristics impact on their delivery of EBP and cause therapist drift . Some clHowever they do not represent good targets for intervention due to their stability and there are other, potentially more modifiable characteristics such as clinician anxiety levels, which also seem to impact on a clinician’s ability to deliver evidence-based exposure-based techniques in the treatment of a range of anxiety and eating disorders , 30. DeaAs the clinician is the primary agent in delivering EBP, exploring specific characteristics that may impact on their ability to change and adapt is useful. The consideration and integration of clinical research, the application of knowledge, and the delivery of EBP may be considered forms of clinician behaviour. If these clinician behaviours are open to change, we can utilise a framework to support clinicians towards behaviours that will improve client outcomes. One of many frameworks within behaviour change theory, such as social cognitive theory (SCT)  may infoTherapeutic optimism can be described as a characteristic of the clinician that focuses on outcomes of others in our care , and resThese findings warrant further investigation into the clinician characteristics of self-efficacy and therapeutic optimism. Results could be used to guide education, training and support needs for psychologists, specifically to enhance their adherence to EBP and further improve outcomes for clients and reduce the burden on the healthcare system.The aim of the current study was to examine the relationship between treatment fidelity in CBT for eating disorders and the clinician characteristics of self-efficacy and optimism in a sample of psychologists. Specifically, it was hypothesised that both clinician self-efficacy and therapeutic optimism would be positively associated with treatment fidelity.The participants were 100 psychologists who all identified as either a provisional (intern), registered or clinical psychologists. For participants to be included in the study, they had to be a provisional, general or clinical psychologist identifying as practicing CBT and to have had a case load that comprises of a minimum of one eating disorder client over the past 12 months. Three psychologists who completed the survey did not meet these criteria and were excluded. The survey was activated by 160 participants of whom: two had not seen an eating disordered client in the past 12 months; one did not utilise CBT; one was a psychiatrist; 17 did not respond to any of the questions; and 39 did not complete the full survey. This resulted in 100 individuals who completed the full survey.Green  providesAn online survey was designed to retrospectively assess clinicians’ self-reported adherence to EBP CBT in treating individuals with eating disorders and obtain additional information regarding a range of clinician characteristics. Participants were psychologists sourced through advertisements, via email, social media and web pages, with a range of organisations including the Butterfly Foundation, Australian Association of Cognitive Behavioural Therapy, Australian and New Zealand Association of Eating Disorders, National Eating Disorder Collaboration, Centre for Eating and Dieting Disorder and eating disorder interest groups. The survey was available for completion from February to July 2017.Data were gathered via an online survey using Qualtrics. The survey was structured to avoid priming participants, including randomised presentation of questions and they were unable to return to questions to amend answers. The survey consisted of five parts which included demographic and professional information; questions on knowledge translations strategies; self-reported knowledge of CBT for eating disorders; self-reported treatment fidelity for CBT for eating disorders; and clinician self-reported self-efficacy and optimism regarding the delivery of CBT for eating disorders.Participant demographic variables were collected including age, gender, ethnic background and location. Information related to their professional status was obtained including professional title, options included provisional (intern or higher degree student), registered or clinical psychologist. Other data included provisional pathway to registration, clinical endorsement and location of professional training. Further information was gathered related to their practice in the eating disorder arena such as percentage of current case load of eating disorder clients. Information regarding the clinician’s use of knowledge translation strategies was collected, including attendance at eating disorder-specific training, utilisation of eating disorder-specific supervision and use of a training manual.Clinician Knowledge of CBT-based treatment for eating disorders was measured by requesting participants to review one of two modified vignettes that had been used in earlier research [research , 47. Theresearch  diagnosiresearch . The cliTreatment fidelity was the dependent variable and measured by clinican self-rated use of CBT in a clinical setting for BED and BN. The participant was requested to state with what percentage of their clients would they use a range of techniques. The clients were to have presented in the last 12 months and have similar presentation to the one viewed in the vignette (BN or BED). The techniques were as per those utilised for the measure of clinician knowledge, which included eating disorder-specific, generic CBT, or non-endorsed techniques. The treatment fidelity score was derived by taking a mean of the percentage clinicians use the six eating disorder techniques. The overall score ranges between 0 and 100 with high scores reflecting high levels of treatment fidelity and low scores indicating low levels of treatment fidelity.Clinician Self-Efficacy in treating eating disorders was assessed using a modified version of the 10-item Personal Efficacy Beliefs Scale, which was first validated for job-related applications in a work setting [ setting . The modClinician Therapeutic Optimism in treating eating disorders was assessed using a modified version of the 10-items Therapeutic Optimism Scale [sm Scale . The modBivariate relationships between variables were explored using Pearson and point-biserial correlations. To test the hypothesis that self-efficacy and therapeutic optimism may account for a significant proportion of the variance in clinician treatment fidelity beyond that already accounted for by clinician eating disorder knowledge, a hierarchical multiple regression analysis (MRA) was employed. Treatment fidelity was entered as the dependent variable. To control for the level of knowledge this variable was entered at step 1, followed by the individual predictor variables of self-efficacy and therapeutic optimism at step 2. Only variables that significantly correlated with treatment fidelity were included as predictors in the model. The data were screened for normality and checked for assumption violation. Despite knowledge and treatment fidelity scores being slightly positively skewed when entered into the regression, the residuals were normally distributed and there was no other evidence of multivariate non-normality, non-linearity or heteroscedasticity.The demographic factors of the final sample are shown in Table The sample consisted largely of females in their mid-30s and included an equal proportion of non-higher degree pathway clinicians  and masters/doctorate degree pathway clinicians , with fewer trainee psychologists. There were eight trainee psychologists, seven completing the higher degree clinical masters and one the non-higher degree pathway. As no relationship was found between years of training and treatment fidelity, these eight psychologists were assigned to either clinical or general psychologist groups accordingly. There was a range of experience from those who worked solely with eating disorder clients to those that had minimal exposure to this group. Most psychologists had trained and resided in Australia.Table There were a range of generic CBT techniques that were used the majority of the time such as looking at links between thoughts, feelings and behaviors, homework tasks, CBT formulation diagrams and thought challenging. Likewise, core components of eating disorder-specific techniques were stated to be used with a large proportion of individuals such as psychoeducation regarding eating disorders and how they develop and the introduction of regular eating. Nevertheless, some evidence-based techniques were less regularly utilised than would be expected, such as exposure to feared situations/foods and weekly weighing. There were also a number of unsupported CBT techniques that were employed at least half of the time, which included relaxation techniques, motivational interviewing and mindfulness.Analysis examining the relationship between professional variables and treatment fidelity are reported in Table The correlations between clinician treatment fidelity, clinician knowledge, self-efficacy and optimism are presented in Table As predicted, treatment fidelity scores were positively correlated with clinician knowledge (high), self-efficacy (moderate) and therapeutic optimism (low). Results of the MRA are shown in Table Self-efficacy was positively associated with treatment fidelity. Contrary to expectations, therapeutic optimism had significant low correlations with treatment fidelity but in the MRA model with knowledge and self-efficacy, it did not predict treatment fidelity.Eighty-seven respondents indicated using one of the three knowledge translation strategies listed, and all three were significantly associated with treatment fidelity Table . FurtherClinician report of how they accessed eating disorder training highlights a large proportion of them accessing training online (30%) or with facilitators from overseas (45%). 37% of clinicians participated in training delivered by Australian facilitators and only 5% had been provided with training in eating disorders as part of their postgraduate university training. Note that several clinicians utilised more than one training method.This study explored the relationship between clinician characteristics of self-efficacy and therapeutic optimism and how they impact on the delivery of EBP in eating disorders. As anticipated our results suggest that increased clinician self-efficacy is associated with higher levels of adherence to EBP. Furthermore, after controlling for clinician knowledge, self-efficacy remained a significant predictor of treatment fidelity.The hypotheses that therapeutic optimism would be associated with treatment fidelity was not confirmed. One possible explanation for this is that a moderate correlation was identified between the two variables self-efficacy and therapeutic optimism. When entered into a MRA, there was a significant amount of shared, rather than unique, variance and self-efficacy had a greater exclusive influence on treatment fidelity than therapeutic optimism. It may be that therapeutic optimism alone will not produce high levels of treatment fidelity if the core competencies (knowledge) and/or self-efficacy are lacking. Thus, the measure of therapeutic optimism is primarily related to the clinician’s hopes for positive treatment outcomes rather than with their own sense of proficiency of the treatment protocol. It is possible that once a clinician reaches a level of self-efficacy, their degree of therapeutic optimism moderates the relationship between self-efficacy and treatment fidelity. The current findings are partially consistent with the view of Bandura , in thatOne important finding relates to the training of clinicians in the area of eating disorders. Strengthening clinician self-efficacy appears to contribute to improving evidence-based practise in the treatment of BED and BN. By identifying a clinician’s level of self-efficacy via the use of a specific tools, such as the PEBS-ED utilised in this study, supervisors could tailor their support to develop a personalised training plan promoting the effective delivery of EBTs by their supervisees. For example, the support provided to those with high levels of self-efficacy may be limited to guidance around managing challenging clients or atypical presentations. Conversely, those with low self-efficacy may require considerable support, intensive training, access to a formal protocol, as well as regular supervision which may involve observation, role playing and co-therapy, in order to increase their sense of self-efficacy especially in delivering specific strategies they may question or feel anxious administering.Consistent with previous findings , 13 coreThe research differs considerably to these clinician beliefs, suggesting that clinicians can effectively deliver a highly manualised treatment protocol to those with severe mental illness and comorbidity, without compromise to the structured sessions or impact on the therapeutic relationship , 51. TheStrategies for improving clinician delivery of EBP include formal training of clinicians in treatment protocols, clinical supervision and the use of treatment manuals . ManualsEating disorder-specific training for BN and BED was utilised by 64% of clinicians. Interestingly 30% of those had accessed online training; 45% attended training with international professionals; 37% with Australian clinicians, with only 5% reported completing eating disorder training as part of their postgraduate study. An important issue emerging from these findings is the apparent lack of training opportunities in CBT for eating disorders in Australia during postgraduate study, and post registration as a psychologist. This is consistent with prior findings that despite there being a significant demand for training in psychological treatment practices, access to specialist training and supervision can be challenging and expensive .Manuals and short training courses are helpful but fall short of the treatments used in randomised controlled trials, where regular and intensive supervision supplements training. This emphasises the importance of not only didactic training and guidance through a formal protocol and manual, but also regular supervision by a qualified clinician specialising in eating disorders who can assist to translate this knowledge into the delivery of EBP. Surprisingly, data revealed that only 57% of clinicians were accessing supervision to support their work with eating disordered clients. This is concerning especially given that standards for maintaining registration as a psychologist in Australia require a minimum number of supervision hours per year. Outcomes from this study demonstrate that all three of these strategies; clinical supervision, use of a manual and training, are helpful in improving treatment fidelity in CBT for eating disorders. There were no particular combinations or individual strategies that were superior, but results showed that the more strategies utilised, the higher the clinician adherence to treatment fidelity. Supervision may be the one strategy with an individual, interactive framework that can assist in determining clinician self-efficacy, setting suitable personalised goals and identifying strategies to improve clinician deficits in delivering EBP.It is suggested that the optimal environment to utilise a range of knowledge translation strategies is University training at postgraduate level, where theoretical models and formulation are incorporated into the delivery of treatment within internal or external clinical placements. We know that the scientist practitioner model is utilised in the majority of training institutions for clinical psychology in Australia . It woulThere are some limitations to the current study which should be considered. One main limitation is that the study assessed self-report of treatment delivered retrospectively over the past 12 months, with a varying number of eating disorder clients; an indirect measure of treatment fidelity. It would be important for future studies to focus on obtaining direct measures of treatment fidelity to reduce bias and subjectivity of answers.Secondly, whilst the scales used to evaluate self-efficacy and therapeutic optimism were based on other scales validated in studies of other healthcare providers, they have not been used in previous research. Further validation of these scales with a psychologist population would be an important focus for future research.An extension of the literature on self-efficacy may include examining its relationship with treatment fidelity with other therapies in a range of mental health conditions where there is evidence of therapist drift, to determine if the findings of this study apply and extend to other areas of clinical work in psychology. A diverse range of healthcare clinicians deliver CBT for eating disorders including occupational therapists, psychiatrists, mental health nurses and social workers. It would be pertinent to explore outcomes for a range of professions and how they relate to the different professional training frameworks. Future research extending our understanding of other clinician characteristics amenable to change and that impact on delivery of EBTs, would be useful and could be targeted as part of supervision or personal development.As findings show that clinicians are not utilising exposure-based techniques in CBT-based therapies across a range of disorders, future dismantling studies would be valuable in determining which specific components of CBT for eating disorders are most effective and the essential components of treatment. A recent systematic review and meta-analysis  has showIt would be important to survey Australian institutions to determine what elements of eating disorder training, are incorporated into training programs. The postgraduate years would certainly be an optimum time to expose early career clinicians to the area of eating disorders where they have access to a range of knowledge translation strategies as part of a structured evidence-based program, giving rise to a greater number of quality treatment options in the community.Improving clinician self-efficacy appears useful in improving evidence-based practice in the treatment of BED and BN. These findings may have implications and be an important consideration in the training of clinicians. Knowledge translation strategies such as supervision, training and the use of manuals are valuable in enhancing clinician adherence to evidence-based practice. Further research with direct measures of treatment fidelity is needed to clarify these findings.Additional file 1:Questionnaires: PEBS-ED and TOS-ED. (PDF 89 kb)