The invasive fall armyworm (FAW) is threatening maize production and the livelihoods of millions of smallholder farmers in the newly invaded areas in Africa and Asia. To control this new key pest and to overcome health, environmental, and resistance problems related to the indiscriminate use of insecticides, effective and sustainable alternative pest control approaches are needed. Here, we report on field trials that tested maltodextrin, neem-based products, ash, and soil, as well as the locally produced alata samina soap, in the Upper West and Greater Accra regions, Ghana. Significant reductions of larval numbers and crop damage, together with increased yields, were mostly achieved by applying the insecticide emamectin benzoate, which was considered the positive control in this set of trials. However, high efficiency and cost–benefit ratios were also achieved with two neem-based products. Maltodextrin was only efficient at one of the two sites, with a clear dose-dependent effect, while the higher dosage was nearly as effective as emamectin benzoate. Due to its relatively high product cost, maltodextrin is generally less cost-efficient. Ash and soil, as well as alata samina soap treatments, did not efficiently reduce FAW larval numbers or crop damage at the dosages tested; thus, they also did not significantly increase maize yields. Spodoptera frugiperda (J.E. Smith), is a polyphagous migratory insect pest that is able to cause considerable economic losses in over 80 different crops [The fall armyworm, nt crops . The pesnt crops , and by nt crops ,4. Recennt crops .S. frugiperda threatens the food security of hundreds of million people. Farmers in the invaded area were not prepared for this devastating pest, resulting in heavy losses on one hand, but also a drastic increase of insecticide use on the other [As maize is a staple food in most African countries and also the second most important crop in Asia, the invasion of he other . Farm hohe other . Such ovhe other ). Moreovhe other ). TherefTelenomus remus, is already present in Africa [Aiming to solve these problem more sustainably, the importation of natural enemies from the native area of the pest for release and permanent establishment in invaded areas  may be considered. A candidate for biological control, n Africa , so it rn Africa . CurrentAltogether, a strong need exists to identify alternative solutions for farmers that would be effective, affordable, in line with Integrated Pest Management (IPM), and tailored to suite the local conditions and farming practices in Africa ,13,14. IAzadirachta indica Juss.), of which extracts from pods or leaves are known to possess pesticidal properties [A recent review on the potential of microbial substances, including entomopathogenic fungi, entomopathogenic nematodes, bacteria, and baculoviruses, to control FAW was published by . Despiteoperties ,21,22, aoperties . Soap haoperties . Even thoperties , and genoperties ,27.In general, all of the above alternative solutions barely have a pre-harvest interval, have no relevant residues, and are safe for applicators and consumers. However, rigorous testing of their efficacy in the context of African small holder farmers is mostly lacking. Hence, field trials were conducted in Ghana, with the aim of testing the efficacy of the aforementioned indigenous strategies for the management of FAW in maize, and ultimately with the aim of developing recommendations that can be used at scale.This field experiment was established at two study sites. The first site (site 1) was located at the Council for Scientific and Industrial Research—Savanna Agricultural Research Institute (CSIR-SARI) at Tanina in the Wa West District of the Upper West region, Ghana. The site is located at an altitude of 368 m and belongs to the Guinea Savanna zone. The region has a unimodal rainfall pattern with a peak between May and October, and a mean total annual rainfall of about 1050 mm. During the main 12 weeks of trial implementation, 405 mm of rain were observed in total, with a weekly mean of 33.7 ± 17.5 mm. Planting was done on 18th July 2018 after the first rains provided good conditions. Approximately 470 mm of rain was subsequently observed between mid-July and the end of October, when the trial crop was harvested. Basal fertilizer application of 100 kg/ha NPK (23-10-5) was done two weeks after crop emergence, while top dressing with 50 kg/ha sulphate of ammonia (21% N) was done three weeks after basal application. Weed control was done manually. The soil in the experimental area belongs to the Savannah Ochrosol type, with a relatively thin layer of top soil (about 25 cm deep) consisting of greyish brown loamy sand.®, 537.5SE), with manual weeding afterwards as needed. Two weeks after crop emergence, 100 kg/ha NPK (15-15-15) was applied to maize seedlings, with about 2 g placed near individual plants into small holes. A month after the initial fertilizer application, 50 kg/ha of sulphate of ammonia was applied to the crop.The second site (site 2) was located at the research farm of the Biotechnology and Nuclear Agriculture Research Institute (BNARI) of the Ghana Atomic Energy Commission, located in the Ga East Municipality of the Greater Accra Region of Ghana, at 52 m above sea level, with rainfall following a bimodal pattern. The experiment was carried out during the minor cropping season, which shows rather erratic precipitation. During the main 12 weeks of trial implementation, 1383 mm of rain was observed in total, which is more than the long-term average, with a weekly mean of 115.2 ± 84.3 mm. Planting was done on 6th September. The soils of the study area belong to the Savannah Ochrosols subgroup, which is characterized by very shallow, reddish-brown and brown concretionary soil, which is medium to light textured. For weed control, a pre-emergence herbicide was sprayed the day after sowing  maltodextrin, (2) neem products, (3) ash and soil, as well as (4) alata samina . Unless otherwise specified, the following applies to all four trials, while for treatment details we like to refer to the specific trial description in . For allMonitoring of the complete trial site for FAW was carried out regularly immediately after emergence of the crop. The treatments were imposed when approximately 10% of plants overall were showing signs of infestations with FAW. The first application of treatments was done on 15th August at site 1 and on 19th September, 2018, at site 2. Two more applications were then done at site 1, while only one more application was done at site 2. The treatments were applied using knapsack sprayers, which were always thoroughly cleaned after use. Treatments were done until run-off from the plants started to occur, based on approximately 200 l/ha early in the cropping stage and 300 l/ha after 36 days of crop establishment.During the trial period, data were generally collected directly before treatments were applied and seven days afterwards, resulting in six assessment dates for site 1 and four for site 2. On each assessment date, 20 plants per plot were sampled by walking 2 times diagonally through the plot, assessing 10 plants each. The following data were collected per plot by summing up the figures from the 20 plants: the number of egg masses; the number of larvae (non-destructively); crop damage, for which the Davis scale  was used to assess damage by FAW to maize plants; phytotoxicity, including modifications in color, necrosis, or deformations on sampled plants; and key natural enemies .In addition, during harvest, the percentage of cobs with characteristic signs of FAW damage was assessed based on 20 randomly selected plants per plot (site 1) or 40 randomly chosen cobs (site 2). Finally, the yield was assessed per plot by collecting all healthy grains from the 6 inner rows  and weighing these after the grains had been sun-dried to 12% moisture content.Streptomyces avermitilis. It is not known to cause human health hazards, but is toxic to honeybees and aquatic organisms [In this trial, three maltodextrin treatments , and 0.8%) were established, based on Eradicoat containing maltodextrin (282 g/l), obtained from Certis UK and Ireland. In addition, a negative control (no insecticide) and a positive control  at 0.17% were also implemented. Emamectin benzoate is an insecticide based on emamectin, which is produced from fermentation of the soil actinomycete rganisms . TreatmeIn total, the following six treatments were implemented for this neem trial: Grow-Safe neem oil, applied at 0.17% (low dose); Grow-Safe neem oil, applied at 0.33% ; Ozoneem oil, applied at 0.17% (low dose); Ozoneem oil, applied at 0.33% ; the untreated control; and emamectin benzoate at 0.17% as a positive control. Grow-Safe neem oil is produced by Green-Gro Ltd., Ghana, and was purchased from the manufacturer, while Ozoneem oil, produced by Ozone Biotech, India, was purchased from Karsam Macro Ltd., Ghana. Grow-Safe was mixed with liquid soap (provided by the manufacturer) at a concentration of 0.67 ml/l solution before application, but Ozoneem oil was applied without extra additives because this commercial product already comprises the complete formulation. Treatments were applied at three weeks intervals.Soil material was collected from the experimental fields  and ash was collected from local firewood from a designated team member’s house. In addition to the positive (emamectin benzoate at 0.17%) and negative controls, the following four treatments were applied: (1) Ash applied by hand, 2–3 ml per whorl, equaling about 650 ml of ash per plot. As the crop matured (from 36 days after sowing onwards), the dosage was doubled to 5 ml per whorl. (2) Ash solution applied by knapsack sprayer—650 ml of ash was mixed with 2.25 l of water . As the crop matured (from 36 days after sowing onwards), the dosage was doubled to 1300 ml of ash per plot, mixed with 4.5 l of water per plot. (3) Local soil, sieved with a 2 mm mesh and applied by hand. For this, 2–3 ml per whorl were applied during early crop stages and the amount was doubled as the crop matured. (4) Local soil mixed with ash from local firewood, at a ratio of 50:50 and at 2–3 ml per whorl, which was again doubled as the crop matured. Unlike for the neem and maltodextrin trials, treatments here were applied at biweekly intervals at site 1.The alata samina soap was purchased from vendors in the markets of Wa and Accra. This soap is made from the ash of the barks of plants that are locally harvested, such as plantain, palm tree leaves, and shea tree bark. It was reported to be effective against insect pests by reducing their population densities in eggplant and okra farms in Ghana . Prior tFor each trial, data were analyzed separately by generalized linear models, followed by Least Significant Difference post hoc tests and focusing on between treatment differences for the following factors: egg mass numbers, larval numbers, plant damage, cob damage, and yield. The phytotoxicity and number of natural enemies were not statistically analyzed because of very low overall numbers . All analyses were performed with SPSS 25.0.Partial budget analysis was used to assess the cost–benefit ratio of all treatments implemented in the study. This was calculated from grain yields (at the market price for maize in either Northern Ghana (GH¢ 1.4/Kg) or Southern Ghana (GH¢ 2/Kg) from early 2019) of individual treatments and the cost of the applied insecticides, biopesticides, or natural products compared to the untreated control. The following costs were calculated for the applied products, based on one treatment and one ha: emamectin benzoate, GH¢ 20; maltodextrin, GH¢ 156 (high dose); Ozoneem, GH¢ 90 (high dose); Grow-Safe, GH¢ 38 (high dose); alata samina , GH¢ 1.33 (high dose). Labor costs for spraying were assumed to be GH¢40/ha in Northern Ghana and GH¢50/ha in Southern Ghana. The same amount was assumed as for the application of sand or ash treatments.The net profit was calculated as the additional yield harvested/ha (in kg) as compared to the untreated control x the market price – total costs of treatments (the sum of product and labor costs). The cost/benefit ratio was then calculated by dividing the net profit by the total costs of respective treatments, indicating how many additional GH¢ one would get per 1 GH¢ invested in plant protection.24,15 = 5.6, p = 0.23). During later assessment dates at site 2 and altogether at site 1, the number of egg masses found was too low  to allow for statistical analysis. Similarly, the number of natural enemies was too low at site 1 to allow for statistical analysis. At site 2, numbers were generally also low , with no significant differences during the first , second , third , and fourth assessment dates .The number of FAW egg masses was assessed throughout the various trials, but was only analyzed statistically for the first assessment date at site 2, where between 5 and 7.5 egg masses per 20 plants were found, with no significant differences across treatments , 12 August , 5 September , 12 September , 26 September , and 3 October , and went down after the first and third application dates at site 1 but not after the second  and 16 October . No significant treatment effects were observed for the first assessment that was done before treatments were applied . or for the assessment on the 9th October, which occurred shortly before the second application date . In general, higher numbers of larvae were observed at site 2 compared to site 1, with regularly more than 1 larvae found per plant.FAW larval numbers were significantly different among treatments on 5 August , 5 September , 12 September , and 3 October   and 16 October , with the positive control showing higher damage levels than the untreated control, but not for 9 October  for the untreated control towards the end of the vegetative growth period ; in the < 0.001) . At site24,15 = 12.9, p = 0.012) . The yield at site 1 was between 1.5 and 2.8 tons/ha, with significant differences between treatments , while the untreated control showing significantly less yield than the positive control and the high concentration maltodextrin treatment (p < 0.05). At site 2, the yield varied between 1.0 and 1.7 tons/ha, without showing significant treatment effects .Cob damage was very highly variable, but significant differences were found for site 1, where cob damage was more than twice as high for the untreated control compared to other treatments (χ= 0.012) . No signThe yield increase at site 1 resulted in positive returns for the maltodextrin treatments, but also due to relatively high product costs, these were lower as compared to the positive control . Less pr25,18 = 5.8, p = 0.32), second , or third assessment dates at site 2 , with insufficient numbers for analysis during later dates, as well as for site 1. Larval numbers at site 1 were not significantly different among treatments during the first assessment date , but were different after first application of various products, for example on the 22nd August , as well as the following dates . Generally, numbers of larvae/20 plants went down over time for all treatments, while the positive control always had the lowest number of larvae and the neem treatments overall showed similar larval numbers compared to the untreated control , second , or third assessments , while significant differences were only found during the last assessment date on 16 October . Here, the positive control showed significantly less larvae as compared to the untreated control and the two neem treatments with the lower concentrations  , with higher values shown for the Ozoneem 0.17% treatment and the untreated control. Significant differences in maize plant damage were also found at the last assessment date , with all treatments showing similar values of 2.5 to 3, except the untreated control. At site 2, virtually no damage was found on plants before treatments were applied, but substantial damage was observed on 25 September, with significant differences observed among treatments . Two more assessments of crop damage revealed no significant differences among treatments on 9 October  and 16 October .Maize damage scores at site 1  were not significantly different during the first assessment data period  . Four we25,18 = 21.2, p = 0.001) with lower damage for the emamectin treatment when compared to the untreated control and the Ozoneem 0.33% treatment , with lower yields for the untreated control compared to all treatments except for Ozoneem 0.33% (p<0.05). No significant differences among treatments were found at site 2, neither for cob damage  nor for the yield .Significant differences in cob damage were found at site 1 , but were different after the first application of the various products , as well as the following dates . Those egg masses found at site 2 were mostly from the positive control. Larval numbers at site 1 were not significantly different among treatments during the first assessment date , but became significantly different at the second date on 25 September , basically due to near-zero values for the insecticide control, with other treatments showing relatively little variation with between 21 and 28 larvae/20 plants. No differences were again found on the third  or the last assessment date on 3 October   B.25,18 = 6.3, p = 0.28) . Significant differences in maize plant damage were, however, found during the last assessment date on 19 September , with the positive control showing significantly less damage compared to all other treatments. At site 2, virtually no damage was found on plants on 19 September before treatments were applied, but substantial damage was observed on 25 September, with significant differences among treatments   or 16 October .Maize damage scores at site 1 were not significantly different during the first assessment date on 15 August before treatments were applied (χ = 0.28) A. Three < 0.001) B. For th25,18 = 28.7, p < 0.001), with higher damage shown for the ash solution treatment and the untreated control when compared to the insecticide control .Significant differences were found for cob damage at site 1 . While no differences could be found between the treatments involving ash and soil and the untreated control, a significantly higher yield was obtained for the positive control based on emamectin benzoate .Significant differences were found for the yield at site 1 only , but were different during the second date  and most of the following dates . Except for the assessment on 5 September , numbers of larvae stayed a relatively high level for all treatments, with only the positive control consistently showing low numbers (p > 0.05).Looking again at site 1 first, the numbers of FAW larvae were not statistically different for the first assessment date  or during the second assessment, after applying initial  or subsequent treatments . This was despite the positive control showing a rather low number of larvae and must be seen in the context of high observed variability , but this changed during the second assessment date  due to low numbers for the positive control (p < 0.05). Significant differences were also found during the third and last assessments after all three application dates , again solely due to low figures for the positive control.Crop damage was not significantly different at site 1 at first  and again on 16 October , which in both cases was driven by the low damage observed in the positive control.At site 2, crop damage was again virtually absent during the first assessment date, but was significantly different on 25 September after treatments had been applied  or grain yield  at site 1 , basically because of the 0.1% soap treatment showing higher values than both the untreated control and the insecticide treatment. Yield at site 2 also differed significantly , with emamectin benzoate showing higher yields compared to all other treatments. The soap treatments did not lead to any yield increases at site 1, and therefore also did not lead to positive cost/benefit values .The recent fall armyworm invasion in Africa and Asia is undoubtedly a major event in terms of pest management and food security in these continents. A number of publications have recently assessed the spread and impact of FAW, as well as farmer practices, in order to fight against the pest ,28. It iIn contrast to the neem-based products, published information on the pesticidal effect of maltodextrin and its use is scarce. However, a recent survey indicated that 4.5% of farmers in Ghana use it against FAW . Even moS. frugiperda for a long time [For the ash- and soil-based treatments, reports indicate that a number of farmers use these methods in Africa ,7,31, asong time .The soap tested here  did not show itself to be effective either, as larval numbers, plant damage, and maize yields were basically unchanged compared with the untreated control. We are not aware of any published study testing alata samina against FAW, but it is reported to have certain fungicidal and insecticidal effects. For instance, Forchibe et al.  found thLooking at the four trials reported on here and our two trial sites, the insecticide emamectin benzoate showed very good performance in six out of the eight cases. In two situations, yield more than doubled as compared to the negative control and the cost–benefit values were highest throughout the trials, with only one of the neem products reaching similar levels. This provides evidence for good activity for at least this tested product and helps explain why most farmers in the recently invaded area use pesticides. Emamectin benzoate is not known to cause human health hazards, however, many African smallholder farmers use other, often cheap chemical pesticides, such as lambda-cyhalothrin and cypermethrin, or even more hazardous ones, such as monocrotophos, dichlorvos, and methomyl , for whiIt is now more accepted that farmers should not panic if FAW infests their maize. They should, however, closely monitor the field situation to see whether rain events or natural enemies reduce the population levels below the economic threshold level. When action to control FAW would finally be needed, however, is still a rather difficult decision to make . There i2, which will help in reducing damage and yield loss, even in the case of severe FAW attack. It is also widely acknowledged that a number of cultural control methods would be important to reduce FAW incidence and the severity of attack [In addition to careful monitoring of the maize crop, it is also strongly advised to ensure a generally healthy crop by considering soil health, fertilization, and even an appropriate number of plants per mf attack .In the present study, we not only assessed the efficacy of the tested products but also calculated a cost–benefit ratio, which is an indicator of the relative economic performance of the treatments. A ratio of more than 1 indicates the economic viability of the treatment compared with the control treatment. As in some treatments even less maize was harvested than in the untreated control, obviously negative cost–benefit ratios were obtained for those, which for this reason they cannot be recommended to farmers based on the present data. Altogether, the cost–benefit ratios obtained here ranged from the abovementioned slightly negative values up to a maximum value of 11.3, thus a significant return on investment in plant protection is possible. Other studies have found ratios in the same range or even higher, particularly when cash crops are considered (e.g., Amoabeng et al. , who worHere, we only tested a small number of potential products and local methods, of which unfortunately several were shown to not be effective. Nevertheless, we believe that more research would be needed, for example for soil, sand, or soaps. There could be different types of materials, different concentrations, or different ways of applying the product that could potentially have a better effect. Also, interaction of these methods with other factors, of which rain is likely an important one, should be further elucidated. Lastly, there are hundreds of plant species with pesticidal properties that have been reported from Africa through farmer surveys and follow-up research, many of which have been confirmed to be active against a range of arthropod pests . Thus, tIn response to the need to achieve sustainable control of FAW, field trials were conducted on maltodextrin, neem-based products, ash, and soil, as well as the locally produced alata samina soap in Ghana. The insecticide emamectin benzoate, which was considered the positive control in this set of trials, overall showed good results in terms of damage reduction, yield increase, and cost–benefit values. If a chemical insecticide were to be chosen, emamectin benzoate might be more preferable than some of the “older” broad-spectrum ones. Nearly as efficient were the neem-based products Ozoneem and Grow-Safe. Neem-based products can, therefore, be recommended as an important component for any integrated pest management scheme to fight FAW. The high dose treatments of the two neem-based products did not have any better effects than the lower dosages, so the reduced dose may be recommended, which also has benefits in terms of optimizing the cost–benefit ratio. The starch-based maltodextrin was only efficient at one of the two test sites, with a clear dose-dependent effect. The relatively high product costs, however, resulted in overall reduced cost–benefit values. Ash and soil applied to the whorl, as well as alata samina soap treatments, did not efficiently reduce FAW larval numbers or crop damage, and thus did not significantly increase maize yields. We still propose further studies with these latter substances, for example with different types of soil, different application methods, or combining them with other insecticidal substances. Since they have very low costs associated with them, any positive effect would immediately increase the farmers’ income.


Netball is estimated to be played by more than 20 million people worldwide, but there is evidence of high injury incidence. A thorough understanding of the types and rates of netball injuries is essential for effective injury management and prevention strategies to be developed and implemented. This systematic review summarises the published findings with respect to injury types, participant characteristics and any identified risk factors for netball injuries.A librarian-assisted computer search of seven scientific databases was conducted for studies reporting on netball injuries. Inclusion criteria were studies published in English, in peer-reviewed journals, which reported data on injuries and variables (e.g. age and competition level) that have been proposed as possibly associated with netball injury risk.Forty-six studies  from 45 articles were included after screening. The majority of studies (74%) were conducted in Australia or New Zealand. There was little consistency in the definition of ‘injury’. Elite or sub-elite level players were included in 69% of studies where the level of competition was reported. The duration of injury surveillance was generally related to the format of competition from which data were collected. Self-report questionnaires were used in 48% of studies and only 26% of studies used qualified health professionals to collect data courtside. Injuries to the ankle and knee were the most common (in 19 studies) although the incidence varied considerably across the studies (ankle 13–84% and knee 8–50% of injuries). Prevention of ankle and knee injuries should be a priority. Children sustained more upper limb injuries (e.g. fractures) compared with adults who sustained more lower limb injuries (e.g. ankle and knee sprains/strains). A large number of potential risk factors for injury in netball have been investigated in small numbers of studies. The main circumstances of injury are landings, collisions and falls.Further studies should be directed towards recreational netball, reporting on injury incidence in players by age and utilising high-quality, standardised methods and criteria. Specific injury diagnosis and a better understanding of the circumstances and mechanisms of injury would provide more meaningful data for developing prevention strategies.The online version contains supplementary material available at 10.1186/s40798-020-00290-7. Injury rates increase with increasing age, and the most common sites of injury change from the upper limb  in those < 16 years to the lower limb (particularly ankle and knee sprains and strains) in adults.Existing evidence suggests that injury rates appear higher in elite players (19.35/1000 PH) than recreational players (11.3–14/1000 PH) and in matches than in training.Common circumstances of injury are jump-landing, trips/slips/falls and contact with another player or the ball.More centralised national databases incorporating quality injury diagnosis across all competition levels would improve our understanding of injuries in netball.The International Netball Federation (INF) has estimated that more than 20 million people play netball in more than 70 countries . NetballWhile netball is a sport with one of the highest participation rates, there is also evidence of high injury rates, with comparisons being made to other team sports including all football codes, basketball, field hockey and cricket –9. InjurThe conduct and reporting of this review adheres to PRISMA guidelines .Studies were included if they reported data on netball injuries sustained by netball players of any age, sex or competition level, were full-text peer-reviewed articles and published in English. Included study designs were observational and experimental. Case studies, reviews and conference abstracts were excluded. Included studies reported data on netball injuries in general and/or in relation to variables such as age, competition level or any other factors associated with netball injury or injury risk. Studies were included regardless of injury definition; i.e. any injury definition was acceptable provided the injury was related to netball matches or training.A biomedical librarian assisted with the development of the search strategy for a systematic search of the electronic databases Cinahl, Medline, Embase, Cochrane, Informit Health, Scopus and SPORTDiscus from 1985 to 20th January 2020 (completed on 20th January 2020). The search was limited to 1985 as the paper by Hopper  is regarAfter removal of duplicates, two reviewers independently screened titles and abstracts. If there was uncertainty regarding inclusion of identified articles, the full text was obtained and screened. Discrepancies were first independently re-assessed by each reviewer, then resolved following independent assessment by a third reviewer. Agreement between reviewers was calculated using Cohen’s Kappa . The quaData from the included studies were extracted by one reviewer and verified by a second in a database template. Data included quality assessment information, country of origin, participant characteristics , data collection period and methods, injury definition, player exposure, injury rate or proportion, injury site, type and severity and key study findings. Results of studies were summarised qualitatively for comparison. Quantitative assessment was limited to tallying the number of studies reporting a particular issue.κ = 0.59, 95% CI: 0.51–0.68) and very good , respectively. The main reasons for exclusion were that no injury data were reported or publication was not peer-reviewed. Only two articles [The search identified 434 articles after duplicates were removed. After screening, 45 articles were included in the review Fig. . The intarticles , 16 werearticles  reportedarticles  and Coetarticles  used datarticles  and Hopparticles  also usearticles   in Australia, 8 (17%) in New Zealand, 5 (11%) in South Africa, 3 (6.5%) in the UK, 2 (4.3%) in Malaysia and 1 (2.2%) each in Singapore and Jamaica.n = 14, 30%), prospective studies at tournaments , retrospective studies  and studies accessing database sources, including hospital and insurance company records . One article [The studies are presented in Table ords n = , 37%. Onn = 7) of studies having< 100 participants. Injury numbers ranged from 11 to 608, with 43% (n = 6) reporting < 25 injuries. In prospective studies over the course of a tournament, participant numbers ranged from 192 to 1280, and injury numbers from 52 to 205. In the retrospective studies, participant numbers ranged from 16 to 1084; 88% (n = 7) of studies had < 254 participants. Injury numbers ranged from 16 to 504 with most studies reporting < 100 injuries. Injury numbers in the hospital, clinic and insurance records studies ranged from 3 to 5,263 with nine of the studies reporting > 1000 injuries.Among prospective studies during competition seasons, participant numbers ranged from 17 to 11,228, with 50%  studies , 42, 44,n = 9) investigated injuries in the previous two weeks [n = 1) [n = 6) [n = 2) [n = 8) [Of the prospective studies, six 30%) were conducted over less than one week (tournaments) , 36, 37.% were cowo weeks , previouwo weeks , previouwo weeks , during wo weeks  or all pwo weeks , 40, 42 wo weeks . The hos [n = 1) , 1 year  [n = 6) , 51, 54, [n = 2) , 9 or 4  [n = 8) , 53, 55.In the prospective studies, physiotherapists diagnosed and recorded injuries in 10 (50%) studies , 33, 37,In the prospective studies, 11 55%) studies , 36, 37 % studiesTable Only one prospective study  did not Match and training exposure were reported in eight (57%) of the season competition prospective studies –33, 35. n = 6) [n = 4) [n = 5) [n = 3) [A variety of methods were used to report injury rates and incidence. Of the prospective studies, 11 55%) reported injury incidence per 1000 player hours (PH) , 32–37. n = 6) , 50, 51, [n = 4) , 24, 49  [n = 5) , 54, 55,% reporte [n = 3) , 52, 53.Hopper et al.  reportedn = 19, range 13.3 to 84.3% [n = 19, range 8.3 to 50.0% [n = 8, ranged from 36.4 to 85.3% [n = 11, ranged from 3.8 to 54.4% [Forty-three studies 96%) provided some data on injury site in terms of body area. There were various methods of categorising body areas among the studies, some more specific , others more generalised (e.g. lower limb injury) Table . Fifteento 84.3% –43, 48; to 50.0% , 40–42. % provideto 85.3% , 52, 54,Thirty studies (65.2%) provided indications of the tissue damaged. Seven studies reported data on injury recurrence, with reports of 26.2–36.5% , 23, 36 Ligament sprains  , 42, 54 Sixteen studies (34.8%) used descriptive categories, for example, mild, minor, moderate, severe, new, recurrent and overuse. Many authors stated that most netball injuries are minor, but the rates and definitions of minor, moderate and severe injuries varied among studies. Ferreira et al.  reportedMcKay et al.  found thSixteen studies (34.8%) reported factors associated with the circumstances of injury (COI). Hopper  found thst quarter whereas more recurrent injuries occurred in the 2nd quarter. Langeveld et al. [n = 6 and 4, respectively). Hume [Ten 21.7%) studies reported on some aspect of timing of netball injuries. Five studies (10.9%) included data on the time and/or the quarter in the game in which injuries occurred , 23, 28.d et al.  reportedd et al.  investig.7% studiFour studies (8.7%) reported on playing surface in relation to injury frequency. Studies reported a lower injury incidence on synthetic surfaces compared with concrete , bitumenFifteen studies 32.6%) included data relating injury incidence to age. Most studies reported a higher injury incidence with increasing age 2.6% incl, 54, 55,A higher injury incidence was reported in elite or higher grade players compared with lower grade players , 29, 41.Seven studies reported on the specific position or a group of positions (attacking or defending) being played at the time of injury , 42, 44.A number of factors were reported as increasing risk of injury. Attenborough et al.  reportedHopper and colleagues investigated a number of podiatric variables , 40, as th in presentations after rugby union, rugby league and soccer in New Zealand. Hassan et al. [A number of studies compared netball injury presentations to those of other sports. McKay et al.  reportedn et al.  found nen et al.  found nen et al.  found nen et al.  found nen et al.  comparedOnly two studies , 35 repoThis systematic review presents the first summary of the published literature on netball injuries. Forty-six studies published in 45 papers met the inclusion criteria. Twenty studies were prospective, nine were retrospective, and 17 were analyses of hospital/clinic records or insurance claims. Not surprisingly, all the studies were from British Commonwealth countries with most conducted in Australia, New Zealand or South Africa. Injury rates over a netball season of 11.3–14/1000PH were reported in recreational players whereas in elite players 19.35/1000PH was reported . InjurieA number of points are clear from the studies included in this review. Firstly, 87% of the studies were conducted in Australia, New Zealand or South Africa, with very little representation from the other 73 countries who have netball organisations. Australia and New Zealand have, in recent times, been the two dominant nations in international netball competitions. This success may reflect the high proportion of these nations’ young and recreational populations participating in netball. High participation incurs an associated injury impact and cost, and therefore, possible available funding from governments to research injury incidence, type and risk factors in netball.Second, most studies included players across a wide age range with little reporting of the results by age. Children < 16 years) were included in 92% of the database studies, 63% of the retrospective studies, but only 39% of the prospective studies. It is generally acknowledged that hospital and insurance data do not provide a complete picture of the volume or type of injuries that occur in a sport but do identify those that are the most serious  years we reportedThird, competition level was reported to influence injury rates, which has also been described in other sports , 58. StuA number of potential risk factors for injury in netball, in addition to age and competition level, have been investigated, mostly in only one or two studies. Those reporting increased risk of injury included poor balance , 44 and The method of injury data collection used in the studies varied, with many studies using unqualified personnel, for example students or team managers, and this reporting was particularly influenced by the level of competition of the players. In the season-competition prospective studies, those conducted on recreational players only obtained their data by self-report , 22, 32.Injury rates were reported using a number of different metrics and some studies focused on particular types of injury only; consequently, consolidating the findings on injury rates is limited. Some of that inconsistency may be related to the fact that 13 of the articles included in this review were published before 2000 , 40, 53,Future studies should aim to use standardised methods, such as those outlined by Fuller et al.  in theirAlthough the proportion of injuries to each body region varied among studies, most netball injuries in those over 15 years were to the lower limb, particularly the ankle and knee. Ankle injuries were far more frequent than knee injuries with the exception of Maulder et al. . There wIt was not possible to determine the extent to which there are multiple injuries associated with a single injury incident. For example, it is possible that slips, trips, falls or collisions could result in injuries to both upper and lower limbs and possibly the head. It is not clear in the prospective and retrospective studies whether all injuries are recorded or only the most severe or memorable injuries. Similarly, in hospital records and insurance claims, it is likely only the most severe injury is recorded.There has been limited standardisation of reporting of COI. In the Coetzee et al.  study, 6Currently, most recreational netball competitions are played outdoors on concrete/asphalt ‘all weather’ courts, and so players are exposed to a variety of weather conditions that may influence the type and incidence of injuries . Elite cTraining data should be reported in future studies to clarify which practices associated with training are associated with injury risk. This should include the type, duration, intensity and frequency of training activities, as well as any injuries that may occur during training. These studies may then be able to identify training practices associated with high injury risk, or the effect of changed training loads on the incidence of injury during games, enabling coaches and trainers to modify training practices and reduce injury risk.The main strengths of this review are the comprehensiveness of the search, the good agreement between reviewers for inclusion of studies, the stratification of the studies into categories and the rigour of data extraction. The main limitations are those that relate to the quality and extent of reporting in the included studies, particularly differences in injury definitions, limited or lack of clarity regarding the use of health professionals to collect data or verify injury diagnosis in recreational players, reliance on self-report data in many studies, and limited reporting of injuries by age or sex.Recommendations for research and practice are 1) for data on recreational players to incorporate a diagnosis by a qualified health professional; 2) for netball injury data to be collected by people trained in injury reporting and ideally stored in a centralised national database; 3) to report data by age group, especially among those < 18 years of age, such as (a) < 10 years, (b) ≥ 10 ≤ 15 years and (c) > 15 ≤ 17 years; 4) to provide data on male players separately if included; 5) to provide more detail on the types of head injuries sustained by netball players, including the extent and severity of concussion injuries; 6) to provide greater documentation of injuries relative to training and/or match load; and 7) to provide stronger evidence of risk factors, particularly in relation to circumstances and mechanisms for netball injuries that can be targeted by prevention strategies and provide teachable suggestions for coaches. This would improve the data available to netball clubs, organisations and sports medicine personnel working with netball communities, and enable them to provide appropriate resources and equipment to manage injuries and reduce injury risk in this large, varied population of netball players.This review found that most netball injuries are to the lower limb, particularly the ankle, and that injuries to the upper limb have a higher rate in those < 16 years old. Severe injuries are fractures in younger players and ACL and Achilles injuries in adults. Injury rates appear higher in elite players than recreational players. Factors often associated with injury include circumstances such as landings, slips/trips/falls, collisions/player contact and being hit by the ball. Further studies should be directed towards recreational netball, reporting on injury incidence in the under 15-year population and utilising high-quality, standardised methods and criteria. Specific injury diagnosis and a better understanding of the link with circumstances of injury would provide more meaningful data for developing prevention strategies. Further classification of data into acute/recurrent/chronic and timing of injuries may provide links to elements in training and games which increase or decrease injury risk. Studies identifying successful injury prevention strategies are also needed.Additional file 1.


In this study, we found that changes of the retina and optic nerve head in primary pulmonary hypertension can be detected by optical coherence tomography angiography. Main parameters may provide useful evidence for the early detection of ocular impairments in patients with primary pulmonary hypertension. To investigate the microvascular and neural changes in primary pulmonary hypertension (PPH) patients compared with healthy controls.Forty-four eyes of 22 PPH patients were included in this observational clinical cohort study, and 44 eyes of 22 healthy participants were enrolled as controls. Optical coherence tomography angiography images were obtained from each participant using the RTVue XR Avanti device with AngioVue software 2.0.Regarding the total macular-associated vessel density, including that of the superficial and deep retina, the optic disk–associated capillary density, including that of the whole image, capillary density inside the disk, and the peripapillary region, was significantly lower in the PPH group than in the control group. There was a similar trend in the retinal nerve fiber layer thickness and the ganglion cell complex thickness, whereas the focal loss volume and the global loss volume were greater in the PPH group than the control group.Changes in the capillary density and thickness of the retina and the optic nerve head in PPH patients can be detected by optical coherence tomography angiography. Parameters including the macular-associated vessel density, optic disk–associated capillary density, retinal nerve fiber layer, ganglion cell complex, focal loss volume, and global loss volume may provide useful evidence for the early detection of microvascular and neural impairments in patients with PPH. Pulmonary hypertension can be classified into different subtypes according to the clinical symptoms, pathological findings, hemodynamic characteristics, and treatment. It may be idiopathic or secondary to other clinical diseases.2 The increase pressure in pulmonary artery leads to an increase in the superior vena cava venous pressure, which elevates the ocular venous pressure, resulting in ocular venous dilation and choroidal congestion; in turn, this leads to stasis of the ocular capillary network, ultimately resulting in serious ocular complications secondary to PPH, including ocular signs, such as proptosis,3 chemosis, dilated and tortuous episcleral vessels,4 and fundus abnormalities, such as hemorrhage, macular edema, central serous chorioretinopathy-like (CSC-like) changes,5 and secondary glaucoma.7 When PPH patients are referred to the clinic, most ocular abnormalities are asymptomatic or nonspecific.8 Traditional ophthalmic examinations, such as determination of the best-corrected visual acuity or intraocular pressure (IOP) and dilated fundus examination, do not have enough power to detect minor changes in the fundus. Fluorescein fundus angiography is one of the most useful examinations for diagnosing and assessing the severity of fundus diseases. However, it is an invasive technique and may not only cause severe anaphylaxis, even in some healthy individuals,9 but also does not allow the quantification of vessels. Optical coherence tomography angiography (OCTA), a noninvasive cross-sectional imaging technique, is frequently applied.10 High-resolution images can be captured and subtle capillary alterations can be distinguished on OCTA, making quantification feasible.12 In addition, some subtle changes in the preclinical stage can be detected, and the lesions can be located. However, there have been no reports of ocular abnormality analysis in PPH by OCTA.Ocular abnormalities are considered to be strongly associated primary PH (PPH), a subtype that accounts for approximately 10% of PH.The purpose of this hospital-based study was to report the signs of ocular abnormalities in PPH patients and changes in the capillary density (CD) of the retina and optic nerve head (ONH), the retinal nerve fiber layer (RNFL) thickness, and the ganglion cell complex (GCC) thickness between PPH patients and control subjects on OCTA.This observational clinical cohort study was approved by the research ethics committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University and adhered to the tenets of the Declaration of Helsinki. Forty-four eyes of 22 PPH subjects were included. After a dilated fundus examination by a very experienced ophthalmologist (the examiner and the subjects were double blinded), 4 PPH patients with fundus changes were included in Group 1 and 18 PPH patients without fundus changes were included in Group 2. Another 44 eyes of 22 healthy participants were included in Group 3 as controls. All subjects enrolled were patients at the Sun Yat-Sen Memorial Hospital from July 2017 to January 2019. The whole process was performed in the hospital, and informed consent was obtained from all study participants. The inclusion criteria included a diagnosis of PPH confirmed by a qualified cardiologist from the Sun Yat-Sen Memorial Hospital. All of the subjects enrolled had never used drugs that might induce PH or other known medicines that might influence ocular function. One subject with severe PPH had been treated with sildenafil to control the disease for more than 10 years.Baseline ophthalmologic examinations could play a significant role in excluding primary ocular region illness. Ophthalmologic examinations, including determination of the best-corrected visual acuity or IOP and slit-lamp and dilated fundus examinations, were performed on the eyes. Color fundus photographs were obtained (7F-ETDRS) , the central corneal thickness, corneal curvature, anterior chamber depth, and axial length were measured using an IOL Master 700R system ; the visual field was evaluated with a Humphrey Field Analyzer , and OCTA was conducted . Basic characteristics, including sex, age, medical history, PPH duration, mean pulmonary artery pressure, and treatment, were collected. The exclusion criteria were as follows: (1) primary ocular disease and (2) known systemic or other predictable factors that might result in ocular complications, such as diabetes, hypertension, and autoimmune disease. The healthy controls underwent the same ophthalmic examination process.µm-wide region and 600-μm-wide region of the macula were scanned. The inner retinal and outer retinal vascular structures were observed in the screening; parameters in the same layer shared the same vascular plexus, and they had interactions with each other. HD Angio Disc 4.5-mm mode was used to capture a 4.5 mm × 4.5 mm area surrounding the optic disk. The area was divided into different sections, and the radial peripapillary capillary (RPC) density in these sections and the peripapillary thickness were automatically calculated by the software AngioVue 2.0. Furthermore, ONH mode was used to assess the images of the macula and the optic nerve fiber. Ganglion cell complex mode was used to measure the thickness of the RNFL, ganglion cell layer, and inner plexiform layer, and all OCTA examinations were performed by two very experienced ophthalmic examiners. The two examiners were doubled blinded to the subjects. Optical coherence tomography angiography images with a scan quality of <6 were excluded.Optical coherence tomography angiography images were obtained using the RTVue XR Avanti OCTA device  with its prototype AngioVue software 2.0. The device operates at a speed of 70,000 A scans per second, a wavelength of 840 nm, and a frequency bandwidth of 45 nm. The split-spectrum amplitude-decorrelation angiography algorithm allows the OCTA device to detect erythrocyte movement noninvasively in real time. Centered on the fovea, both the 300-Forty-four eyes of 22 subjects and 44 eyes of 22 healthy controls were enrolled in this study. There was no statistical significance in age or sex between the PPH and control subjects. Regarding the baseline ophthalmologic examination, there were statistically significant differences in the best-corrected visual acuity and IOP between Group 1 and Groups 2 and 3 . The characteristics of the participants, including the mean age, sex, corneal thickness, anterior chamber depth, and axial length, were not significantly different among the three groups. There was a significant increase in the mean pulmonary artery pressure in Group 1 compared with Group 2, but there was no significant difference in the PPH duration between the two cohorts. The characteristics of the participants are presented in Table 13 Anterior segment manifestations, such as chemosis and dilated and tortuous conjunctival and episcleral veins, are common, and they can be observed not only in PPH patients with fundus changes but also occasionally in PPH patients without fundus changes. Other signs, such as corneal edema, could be assessed in Group 1.14 Moreover, fundus abnormalities, including tortuous retinal vessels, retinal hemorrhage, macular edema, and CSC-like changes, were observed during the dilated fundus examination in Group 1 subjects.15 In our cases, the main ocular manifestations are shown in Table The ocular symptoms reported by the PPH patients with fundus changes were nonspecific and included blurred vision, metamorphopsia as a result of macular involvement, severe eye pain resulting from high IOP, and red eyes because of vascular changes.The parameters compared among Groups 1, 2, and 3 included the foveal avascular zone, macular-associated vessel density (VD), optic disk–associated CD, GCC thickness, RNFL thickness, focal loss volume (FLV), global loss volume (GLV), subfoveal choroidal thickness, and choriocapillary flow area. Statistical analysis of the OCTA data was performed using SPSS 25.0 . The numerical variables were compared among the three groups by one-way analysis of variance, and Least Significant Difference post hoc analysis was performed to evaluate the significant differences.P = 0.003; deep total VD: 45.1400 ± 3.638% vs. 50.184 ± 3.980%; P = 0.003; CD inside the disk (ring diameter = 4.5 mm): 54.170 ± 11.736 vs. 61.984 ± 3.546%; P = 0.000; peripapillary CD (ring diameter = 4.5 mm) 47.055 ± 6.087 vs. 58.813 ± 2.338%; P = 0.000; whole RPC density: 45.788 ± 5.451 vs. 55.952 ± 2.656; P = 0.000). However, there was no significant difference in the foveal avascular zone or foveal VD  between the two cohorts . The perifoveal VD in the superficial retina and the parafoveal and perifoveal VD in the deep retina were lower in Group 2 than Group 3 . There was a similar in the RPC and optic disk–associated CD when comparing Groups 2 and 3 . Additionally, the GCC thickness was reduced in Group 1 . Furthermore, the FLV and GLV were increased in Group 1 compared to the other two groups . Moreover, the differences in the macular-associated VD, optic nerve–associated CD, RNFL thickness, GCC thickness, FLV, and GLV between Groups 1 and 2 were statistically significant. Details are shown in Tables The RNFL thickness was significantly reduced in Group 1 compared with Groups 2 and 3  was observed in the PPH patients compared with the control subjects. The parafoveal VD and the perifoveal VD  were obviously decreased in Groups 1 and 2 compared with Group 3. The macular-associated VD seemed to be influenced in PPH secondary to the increasing PH. Furthermore, there was a significant difference between Groups 1 and 2. It needs to be emphasized that changes in the macular-associated VD occurred in the preclinical stage before ocular symptoms and signs occur in PPH. Group 1 showed a decrease in the foveal VD in both the superficial and deep layers; unexpectedly, there was a mildly increasing trend in the foveal VD of Group 2  compared with Group 3. In the early stage of the disease, PPH involves peripheral vascular resistance, and the resistance and vascular remodeling in the periphery may cause compensatory changes in other vascular beds, including the vessels in macula,21 In PPH, increased ocular venous pressure secondary to increased pulmonary arterial pressure results in elevated episcleral venous pressure, which blocks the aqueous humor outflow pathway and eventually induces secondary glaucoma.In our study, the optic disk–associated CD, including the whole RPC density, the CD inside the disk, and the peripapillary CD, was significantly reduced in the PPH group compared with the control group. Furthermore, a significantly decreasing trend in the optic disk–associated CD was also observed in Groups 1 and 2. Therefore, the chronic retinal hypoxia caused by the stasis resulting from the increased pressure in the choroidal circulation that is induced by increasing pulmonary arterial hypertension may not only contribute to vascular dropout and remodeling in the macular area but also affect the capillaries in the disk. Similarly, neural impairment was noted , CSC associated with sildenafil was observed. However, some results in our study are somewhat unexpected considering such preconceptions because the choriocapillary flow was not significantly different between the groups. The higher content of melanocyte pigment in the choroid and its location below the retinal pigment epithelium may influence the measurement outcomes of OCTA. Therefore, future studies are needed to clarify the possible mechanism underlying this finding.In our study, a significantly greater subfoveal choroidal thickness was observed in the PPH subjects. Increased ocular venous pressure is associated with elevated systemic venous pressure, which affects ocular hemodynamics and causes blood stasis, resulting in thickening of the choroid, and an increased choroidal thickness is a risk factor for CSC. Primary pulmonary hypertension patients have an increased choroidal thickness, and the incidence of CSC among these patients is not unusual.In conclusion, preclinical ocular changes in PPH can be detected by OCTA. Parameters such as the macular-associated VD, optic disk–associated CD, RNFL thickness, and GCC thickness may be useful for the early detection of microvascular and neural impairments in PPH patients with or without fundus changes. Moreover, the deep VD, including the parafoveal and perifoveal VD, and the RNFL and GCC thickness, may be sensitive predictors of ocular impairment in PPH patients without fundus abnormities. This is also the first report to quantify and evaluate vascular dropout and neural impairment in PPH patients.


Increasing use of personal listening devices has been accompanied by increase in the prevalence of hearing loss (HL) among youth in Korea, as in other countries. Auditory processing disorder (APD) is one of the main factors affecting academic achievement at school. This study aimed to investigate the prevalence of HL in students attending general middle- and high schools and compare the findings with the APD survey results. From June 1 to December 31, 2016, Korean adolescents  in the first years of middle- and high school underwent audiometric testing and otologic examination and completed questionnaires on APD. The survey was sponsored by the Korean Society of Otolaryngology-Head and Neck Surgery and the Korean Otology Society. The prevalence of speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) in the poorer ear was 11.6% and 10.3%, respectively, among Korean adolescents. We analysed data from the Scale of Auditory Behaviors, Fisher’s Auditory Problems Checklist, and KNISE-Auditory Behavioral Checklist and compared these with the results of hearing tests. We observed positive correlations among the APD questionnaire results and mean hearing levels. This study suggested that hearing loss, especially bilateral high-frequency hearing loss, may affect central auditory processing. Two nationwide studies have been conducted on adolescents in South Korea: Hong et al. reported unilateral and bilateral HFHLs > 20 dB in 5.0% and 1.9%, respectively, of 1,658 adolescents aged 13–18 years in South Korea2 and Rhee et al. reported that approximately 17% of Korean adolescents exhibited at least slight HL3.With the increasing use of personal listening devices, the prevalence of hearing loss (HL) among the current generation of adolescents has been predictably higher than that among the past generations of adolescents. A study from the USA reported that the prevalence of HL among US adolescents increased from 14.9% in 1988–1994 to 19.5% in 2005–2006. In addition, chronic noise exposure from using mobile devices may increase high-frequency hearing loss (HFHL)4. Because of masking effects from background noise or a hearing problem, the acoustic speech signal is easily degraded, making it difficult to understand. To overcome this difficulty and facilitate speech perception, one strategically adopts some auditory and language-based compensatory mechanisms5. Such language-based mechanisms include semantic and lexical expectations about words presented in context to facilitate speech perception in a noisy environment7. However, unlike adults who have normal language fluency, children in the process of learning a language lack the capacity to “fill in the blanks” for inaudible sounds. Moreover, it is often challenging for children to understand speech under various listening conditions, such as a noisy or a reverberant environment8.Understanding external auditory speech normally and naturally requires at least two stages: auditory processing of the signal and language-based processing of that information9, and approximately 2–5% of school-aged children are reported to be affected by hearing problems10. In addition, a 2017 New Zealand study of youth offenders aged 14–17 years reported that 27% suffered from APD and 64% showed language impairment compared to 18% and 10% of adolescents with normal hearing, respectively11. Children diagnosed with APD have listening difficulties, and many of those who present at audiology or other paediatric clinics have ‘normal’ audiograms. Most of these children have other complications such as speech/language or attention impairments and various learning disorders12.Auditory processing disorders (APDs) are defined as speech perception deficits that exist despite normal peripheral hearing14. Therefore, it must be diagnosed as early as possible. Several test batteries are available to diagnose APDs in patients with normal hearing16. However, several studies have shown that in patients with cochlear HL of up to approximately 45–50 dB, speech perception is mainly influenced by audibility18. In patients with more severe HL, poor discrimination of suprathreshold stimuli plays an important role in addition to the loss of audibility.Although the central hearing difficulty seems to be a single problem, it may be a cause of language disorder, reading disorder, learning disorder, attention deficit hyperactivity disorder, and other problems19. Therefore, having normal pure tone average does not mean that speech perception is normal.However, APD was found in children with normal pure tone average or mild high-frequency hearing lossThe purpose of this study was to analyse the relationship between different degree of HL and results of screening surveys of the central auditory processing ability of middle- and high-school students in South Korea.20.We performed a cross-sectional, complex sampling survey of first-year middle- and high-school students, except those attending special schools for disabled children. The sampling frame was the 2015 Yearbook of Educational Statistics prepared by the Korean Educational Statistics Services22. Details of the study design and research methods are presented in another study2.We sought to enrol 3,013 students from 124 middle schools and 124 high schools based on the prevalence of HL in Korean adolescents, the estimated association between noise and HL, and an expected 80% response rateThe survey was performed from June 1 to December 31, 2016. After providing written information about the study to students and parents, we selected and evaluated only those children who themselves and whose parents provided written informed consent. This study was approved by the Institutional Review Board of Seoul National University Hospital (No. 1604-086-755). All methods/experiments were performed in accordance with relevant guidelines and regulations (Declaration of Helsinki).2. Briefly, four experienced audiologists measured the hearing thresholds of adolescents using an AD229b diagnostic audiometer  in a soundproof booth inside a mobile vehicle. Prior to audiometry, otological examinations were performed to rule out factors affecting hearing, such as external ear anomalies, ear wax, retraction of the tympanic membrane, cholesteatoma, and middle ear effusion.The methods of audiological evaluation are superbly detailed in the previous studyThe tested frequencies were 0.5, 1, 2, 3, 4, 6, and 8 kHz. We started at 30 dB, adjusting with a 10 dB decrease or a 5 dB increase according to the participant’s response, until we decided that his or her frequency-specific hearing threshold was reached. If the hearing threshold was over 25 dB at any frequency, we measured the bone conduction threshold to determine whether conductive hearing loss was present.1. Speech-frequency hearing loss (SFHL) was the average of the HLs at 0.5, 1, and 2 kHz, while HFHL was the average of the HLs at 3, 4, 6, and 8 kHz.We defined HL as a hearing threshold ≥15 dB. The severity of HL was based on the poorer threshold for unilateral HL and better threshold for bilateral HL, as described previouslyThe students were asked to complete separate questionnaires to evaluate their everyday difficulties in areas such as listening, learning, and communication.24. The KNISE-ABC has 36 items rated on a 5-point scale and includes seven test areas, namely, listening, listening in background noise, communication, learning, auditory memory, auditory attention, and related behaviour.The KNISE-Auditory Behavioural Checklist (KNISE-ABC) is used for screening children with APDs and other related disorders to provide information necessary for establishing and implementing management and educational plans25. The questionnaire is easily administered because it has a small number  of questions and answer options that are easily understood. This questionnaire was developed to assess everyday behaviours associated with audition, listening and academic skills, attention, memory, and organisation.The Scale of Auditory Behaviours (SAB) questionnaire, chosen for this study, has a version that may be used by parents or professionals26 and comprises a list of 25 items rated on a 2-point scale. To collect information about the perceived auditory processing problems, this checklist includes questions on acuity, attention, attention span, figure ground, discrimination, short-term memory, long-term memory, sequential memory, comprehension, speech and language problems, auditory-visual integration, motivation, and performance.Fisher’s Auditory Problems Checklist (FAPC) was developed by Fisher Lp-value <0.05.All data in the study are summarised as means and standard deviations for continuous variables and as frequencies and percentages for categorical variables. Comparisons of general characteristics between HL and no HL were conducted using the chi-squared test or Fisher’s exact test. Prevalence rates of SFHL and HFHL were estimated with 95% confidence intervals. To evaluate the association between the degree of HL and mean scores of KNISE-ABC, SAB, and FAPC, we adopted Wilcoxon’s rank sum test. All statistical analyses were performed using SAS , and statistical significance was defined as a two-sided In total, 3,013 students from 109 middle- and high schools agreed to complete the questionnaires. Of these, 134 (4.4%) were excluded because of incomplete audiometric data. Additionally, 88 students were excluded because of incomplete survey tests. Finally, a total of 2,791 (90.0%) students participated in this study .Demographic characteristics of these 2,791 students are summarised in Table The prevalence of any-HL  was 12.8%. In addition, the prevalence of any-HFHL and any-SFHL was 7.9% and 8.3%, respectively; that of unilateral HL, HFHL, and SFHL was 8.7%, 5.8%, and 5.9%, respectively; and that of bilateral HL, HFHL, and SFHL was 4.1%, 2.1%, and 2.4%, respectively. Detailed data are presented in Table . FAPC analysis also revealed no significant difference was observed between students with and without hearing loss in the any hearing loss and unilateral hearing loss groups. However, students with bilateral hearing loss, irrespective of whether they had high-frequency hearing loss or speech-frequency hearing loss, showed significantly worse performance scores than those without hearing loss. Moreover, students with bilateral high-frequency hearing loss showed relatively larger differences than those with other bilateral hearing loss .The KNISE-ABC analysis revealed no significant differences between students with and without hearing loss in the any-HL and unilateral HL groups. However, students with bilateral HL, irrespective of whether they had HFHL or SFHL, showed significantly worse performance scores than those without HL. Moreover, students with bilateral HFHL showed relatively larger differences than those with other bilateral HL Fig. . The SABFig. . FAPC anoss Fig. .Figure 2In this study, the prevalence of SFHL and HFHL in the poorer ear was 11.6% and 10.3%, respectively, among Korean adolescents. There were no significant differences between the no-HL and any-HL groups in sex ratio, grade level of middle- vs. high school, household income, and family history, meaning that environmental factors such as noise exposure might be more influential on their hearing. In addition, when the three degrees of HL  and mean scores from KNISE-ABC, SAB, and FAPC were compared, Korean adolescents with bilateral HL showed significantly worse scores on all three screening tests for APD.27. One or more deficiencies in this ability are referred to as central APD or APD.Auditory behaviour is defined as behavioural characteristics associated with hearing that appear in relation to the process or outcome of receiving and perceiving auditory information in the peripheral and central auditory systems. Children’s hearing behaviour may vary according to the mechanism and function of the central nervous system (CNS). The ability to perceive and manipulate auditory information in the CNS can be used for sound localisation and lateralisation, auditory discrimination, determining the temporal aspects of audition , assessing auditory performance with competing sound signals and acoustic signals, and assessing auditory performance with degraded acoustic signals27. Children with hearing impairment may have problems with overall auditory behavioural characteristics and may exhibit sluggishness or difficulty in certain areas only.Auditory behavioural characteristics resulting from these central hearing processing problems can be caused by or related to difficulties in higher language, learning, and cognitive function. In addition, they may be associated with language disorders, reading disabilities, learning disabilities, and attention deficit hyperactivity disorder17, whereas a less clear distinction can be made using low-pass filtered speech17, binaural interaction, and localisation/lateralisation27. The usefulness of the dichotic test of binaural integration in children was also doubted28. Previous studies have reported these relationships between APD and hearing impairment. Miltenberger et al.29 reported that auditory processing tests must always be related to the basic audiological assessment. They insisted that if the test results do not correspond with expectations based on the peripheral audiological assessment, the presence of APDs is likely, in addition to peripheral auditory disorders. Moreover, in the case of symmetrical hearing thresholds, auditory processing test results should be symmetrical. If the hearing thresholds are asymmetrical and performance in the better ear is poorer than that in the other ear, then an APD could be present21. The problem in APD is a decrease of speech performance in children with normal or mild hearing loss or functional hearing loss31.However, distinguishing between APD and peripheral HL is sometimes difficult; moreover, both problems may sometimes coexist. Peripheral HL does not have uniform effects on the results of APD tests. Studies have shown that cochlear lesions can be clearly distinguished from cerebral lesions using the dichotic-digit test, dichotic sentence identification test, and frequency-pattern test32 or because the loss of the cortical auditory function and high frequency hearing loss occurred simultaneously for some reason. The latter case may be considered as having the same mechanism as loss of speech in noise processing and temporal processing from age-related hearing loss, leading to an increase in APD33. This idea requires further research.In this study, adolescents with bilateral mild hearing loss showed a higher risk of APD. This may be because hearing loss is causally related to functional loss of central auditory processing35, while Neijenhuis et al.16 reported that hearing-impaired patients did not show normal scores on these two tests. As with the results of Neijenhuis et al., in addition to the fact that peripheral sensorineural deafness affects the central hearing process, our results for bilateral HL are the most meaningful. We suggest that adolescents with bilateral sensorineural HL are more likely to have learning difficulties than those with normal or unilateral HL; therefore, more active hearing rehabilitation should be considered for such adolescents.In this study, we adopted three different survey tools—the KNISE-ABC, SAB, and FAPC—for evaluating the ability of central auditory processing among Korean adolescents. All three test results showed that students with bilateral HL, irrespective of whether they had HFHL or SFHL, had significantly worse performance scores than those without HL. Some authors have concluded that HL has only a slight influence on the dichotic-digit and pattern-recognition testsA limitation of this study is that the survey tests conducted to measure the capacity of the central auditory system were originally developed for evaluating children in the elementary school age group. The results of this study showed that only bilateral HL is related to disabilities in central auditory processing and learning; however, in reality, unilateral or various hearing impairments, such as SFHL or HFHL, may be related to learning disabilities in middle- and high-school students. These findings suggest the need for developing a survey to test central auditory processing in students of middle and high school age.Our findings suggest that hearing loss, especially bilateral high-frequency hearing loss, may affect central auditory processing. We should consider providing hearing aid, assistive listening devices, or enforcing educational programs to prevent further noise-induced hearing loss to improve the academic achievement of youth with bilateral hearing loss.


Inter-individual differences in cortisol production and metabolism emerge with age and may be explained by genetic factors.To estimate the relative contributions of genetic and environmental factors to inter-individual differences in cortisol production and metabolism throughout adolescence.Prospective follow-up study of twins.Nationwide register.N = 109 pairs) born between 1995 amd 1996, recruited from the Netherlands Twin Register. Cortisol metabolites were determined in 213, 169, and 160 urine samples at the ages of 9, 12, and 17, respectively.218 mono- and dizygotic twins  and shared and unshared environmental influences to inter-individual differences in cortisol production and activities of 5α-reductase, 5β-reductase, and 11β-hydroxysteroid dehydrogenases and cytochrome P450 3A4.For cortisol production rate at the ages of 9, 12, and 17, broad-sense heritability was estimated as 42%, 30%, and 0%, respectively, and the remainder of the variance was explained by unshared environmental factors. For cortisol metabolism indices, the following heritability was observed: for the A-ring reductases (5α-and 5β-reductases), broad-sense heritability increased with age (to >50%), while for the other indices , the contribution of genetic factors was highest  at age 12.The contribution of genetic factors to inter-individual differences in cortisol production decreased between 12 and 17y, indicative of a predominant role of individual circumstances. For cortisol metabolism, distinct patterns of genetic and environmental influences were observed, with heritability that either increased with age or peaked at age 12y. Cortisol, the main product of the hypothalamus–pituitary–adrenal (HPA) axis, is a crucial steroid hormone in the physiological stress response following homeostasis disturbance . DysreguThere is a paucity of data on the magnitude of the contribution of genetic factors to variance in HPA axis activity. Several studies in monozygotic (MZ) and dizygotic (DZ) twins addressed the relative contributions of genetic and environmental factors on serum and salivary cortisol levels. However, the magnitude of the heritability estimates varies . A meta-Earlier studies have focused on cortisol levels in serum or salivary. These cortisol levels represent the net effect of cortisol production and metabolism. The contributions of genetic and environmental factors to individual differences in cortisol production or metabolism, as determined by cortisol metabolite excretion in urine, have yet to be studied. Day-to-day excretion of cortisol in the urine is moderately stable . CortisoWe conducted a prospective follow-up study in MZ and DZ twin pairs. Participants in this study were recruited from the NTR , 32 and Information on demographics, gestational age, birth weight, and other prenatal and perinatal variables was collected by questionnaire at the time of NTR registration . Twins wBrainScale is a collaborative project between the NTR at the Vrije Universiteit Amsterdam and University Medical Center Utrecht. The project was approved by the Central Committee on Research Involving Human Subjects of The Netherlands (CCMO), and studies were performed in accordance with the Declaration of Helsinki. Parents signed informed consent forms for the children and for themselves. Children signed their own informed consent forms at the third measurement. Parents were compensated for travel expenses, and children received a present or gift voucher at the end of the testing day. In addition, a summary of cognition scores and a printed image of their T1 brain magnetic scan imaging scan, when available, were provided afterward.The current study was approved by the medical ethics committee of the Amsterdam UMC, location VUmc.At the ages of 9, 12, and 17 years, participants visited the study site for different tests. In the week prior to the study visit, urine samples were collected upon awakening in specially provided tubes. Participants or their parents were requested to store the tubes in their refrigerator and to bring them to the study visit. Samples were subsequently stored at –20° and –80° Celsius and thawed only once just before analysis. Urine samples were available from 47 MZ  and 62 DZ twin pairs .Participants were instructed to bring any packages of recently used medication to the study visits, revealing that there was hardly any recent use of medication in our sample.Analysis of cortisol metabolites was conducted at the Edinburgh Clinical Research Facility Mass Spectrometry Core Laboratory. Glucocorticoid metabolites were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS) . SamplesOutliers, defined as any value greater than 3 standard deviations above the phenotypic mean, were excluded from statistical analysis (on average 6 per index). Twin pairs with highly discordant outcomes, as assessed by visual inspection of scatterplots, were also removed , given their impact on the MZ and DZ correlations. We corrected for batch effects by fitting a random effects model to the twin data, which included batch as a random effect . As the MZ) is smaller than 2 times the DZ correlation . With 2 groups of relatives , it is not possible to estimate 4 variance components; that is, a model including nonadditive genetic factors in addition to common environment is not identified. A choice needs to be made to evaluate an ACE or ADE model. If (rMZ>2*rDZ), an ADE model is chosen. Unshared environmental factors incorporates aspects of the environment that are child-specific and results in differences between twin pairs . Unshared environmental factors also includes measurement error. Path diagrams of the ACE and ADE models are shown in The classical twin design exploits the fact that MZ twins share 100% of their alleles identically by descent , and DZ twins, on average, share 50% of their alleles IBD . This diWe used OpenMx to fit the ACE or ADE model to the batch corrected twin data . The genA total of 218 twins who were born in the Netherlands were enrolled in this study, including 94 MZ and 124 DZ twins. The MZ pairs included 23 MZM twin pairs and 24 MZF twin pairs. The DZ twins included 22 DZM twin pairs, 21 DZF twin pairs, and 19 DOS twin pairs. In total, 213, 167, and 162 samples were analyzed at 9, 12 and 17 years of age, respectively.n = 109) of all participants was male. Mean (±SD) gestational age was 36.8 weeks (±1.72), and mean (±SD) birthweight was 2602 gram (±475). Participants were tested at 9.1 (±0.1), 12.2 (±0.3), and 17.2 (±0.2) years of age. Mean standard deviation score (Z score) (±SD) body mass index (weight[kg]/height[m]2) was 0.14 (± 0.93), 0.45 (± 1.00), and 0.26 (± 1.57) at the ages 9, 12, and 17 years, respectively (Fifty percent (ectively .The twin correlations and variances for each index are presented in The relative contributions of genetic (additive and nonadditive), shared environmental, and unshared environmental factors, along with 95% confidence intervals, are displayed in In this longitudinal study of twin pairs followed between the ages of 9 and 17 years, we demonstrated the relative contributions of genetic and environmental factors to the indices of cortisol production and metabolism throughout adolescence. The most important finding from our study is that the environment plays a key role in the production of cortisol, evidenced by the predominant and increasing contribution with age of unshared environmental factors. In addition, we found distinct patterns of genetic and environmental contribution to the different cortisol-metabolizing pathways.A previous meta-analysis of twin studies estimated heritability of basal cortisol, representing the net effect of cortisol production and elimination, at 62% . DespiteIn our study, cortisol production was mainly determined by unshared environmental factors already at age 9, and the contribution of unshared environmental factors was found to increase with age. This lends support to previous observations suggesting that the settings of the HPA axis are mainly determined by individual circumstances . There iIn animal experiments, the influences of early life experiences can be observed by randomly allocating offspring into groups with different amounts of exposure to the factor of interest, whereas in humans determining the long-term impact of life experiences on HPA axis activity is more challenging. Previous research in humans linked early-life experiences like battering, neglect, emotional maltreatment, perinatal malnutrition, low birthweight, and prematurity with future HPA axis activity , 55–58. In our study, cortisol metabolism was, in contrast to cortisol production, considerably influenced by genetic constitution, and our findings suggest distinct patterns of genetic and environmental contribution to the different metabolic pathways. The activities of the A-ring reductases are, unlike cortisol production, less influenced by unshared environmental factors, especially later in life. Variation in A-ring reductases activity was for 0% to 23%, 0% to 51% and 51% to 66% explained by (nonadditive and additive) genetic factors at 9, 12, and 17 years of age, respectively, indicating a predominant role of genetic constitution in the regulation of A-ring reductases with age. The influences of genetic constitution on the activities of 11β-HSD isozymes and CYP3A4 increased from 9 to 12 years and then decreased from 12 to 17 years of age. An explanation for the varying influences found for these enzymes may lie in a complex interplay between cortisol metabolizing enzymes and the hormonal regulators of puberty and the pubertal growth spurt, in particular growth hormone and insulin-like growth factor 1. A previous twin study has shown that the pubertal growth spurt, peaking between 12 and 14 years, is strictly genetically regulated . In addiOur study has several strengths and limitations. The major strength of our study was the long-term follow-up. Furthermore, participants were recruited from a nationwide twin registry, and the numbers lost to follow-up were acceptably low. Consequently, selection bias is unlikely to explain our results. Another strength of our study was the use of GC-MS/MS analysis, providing highly reliable measurements. Thus, the findings as presented are unlikely to be explained by measurement error. However, our study also has its limitations. Participants were requested to collect early-morning urine samples. Preferably, a 24-hour urine sample would have been analyzed, since cortisol is secreted in a circadian rhythm. Next, sampling started no earlier than at age 9, so that there remains a lack of knowledge on the genetic and environmental etiology in early childhood. Moreover, differences between boys and girls were observed, necessitating further research. Additionally, due to limited sample size, resulting in large confidence intervals and some remarkable twin correlations , our results have to be interpreted cautiously. Finally, the collected samples were not randomly distributed across the different analytical batches, which may have led to systematic error. More specifically, samples from twin pairs were allocated in the same batches, which might overestimate the contribution of shared environmental factors. Therefore, random correction for batch effect was carried out.Our current findings, along with previous observations, emphasize the significant role of individual circumstances on the settings of the HPA axis. Notably, the contribution of unshared environmental factors on cortisol production was considerable and was found to increase with age, implicating a predominant role of individual circumstances with aging. In contrast to cortisol production, cortisol metabolism was considerably influenced by genetic constitution, and heritability of A-ring reductases was found to increase with age, resulting in a peak of the genetic contribution at the age of 17. For 11β-HSD isozymes and CYP 3A4, this peak was found at the age of 12.