Visual impairment is a major public health problem. Identifying the main causes of low vision and the major low-vision devices prescribed will help to develop and implement the low-vision rehabilitation service. We find out the causes of low vision and the low-vision devices prescribed in the low-vision clinic of Nepal Eye Hospital. A retrospective cross-sectional review of all patients attending the low-vision clinic from 1 May 2009 to 31 April 2011. Patients having visual acuity less than 3/60 in the better eye with best refractive correction were excluded. Of the 137 patients, the mean age was 32.53 ± 22.90 years; 71.5% were male and 67.88% were under 40. The major causes of low vision were nystagmus (30.70%), high refractive error (22.62%), cataract (15.30%), retinitis pigmentosa (15.30%) and age-related macular degeneration (13.10%); 78.10% patents were wearing glasses while telescopes were prescribed for 29.20% patients. Nystagmus, high refractive error and cataract are the main causes of low vision in Nepal. The majority of the low-vision patients seen in this clinic are of working age. Telescopes are the major low-vision device prescribed. We review approach the cause of low-vision problem in low-vision clinic Nepal Eye Hospital, Nepal. Visual impairment is a major public health problem in developing countries. Someone is described as having low vision if the best-corrected visual acuity is less than 6/18 but equal to or better than 3/60 in the better eye. Moreover, someone with a visual field of less than 10 degrees is also defined as having low vision. People with visual acuity poorer than 3/60 are classified as blind WHO .Functional limitations caused by poor vision occur at visual acuity levels that are much better than the criterion that defines legal blindness  estimated that 161 million and 37 million, respectively, were visually impaired and blind in 2002 worldwide  were also identified. The most frequently prescribed optical devices were also evaluated. This study aims to help the development and implementation of low-vision rehabilitation programmes effectively in this part of world.p < .05)  of the patients were male. The mean age of the male was 34.05 ± 22.85 years while that of female was 28.69 ± 22.89 years. There was significant difference in the numbers of males and females in terms of the age group  .Table 1Most of the low-vision patients seen in this clinic were of working age. This will have consequences for the health and wealth of the public in Nepal. Low vision is known to reduce vision-related quality of life  in the better eye with mode 1.00logMAR; 28% had visual acuity 1.0logMAR and 23% had 0.80logMAR .Figure Almost four-fifths of the low-vision patients seen had some amount of refractive error. Visual acuity can be improved by spectacle correction in many low-vision patients: for example, Sunness and El Annan  have shoThe cause of low vision was iatrogenic in 4 patients, 72 (52.6%) had 1 cause of visual impairment, 35 (25.5%) had 2 causes, 22 (16.1%) had 3 causes and 4 (2.9%) had 4 causes; 30.65% (42) of the participants had nystagmus, 22.62% (31) had high refractive error (≥±5.00D), 18.24% (25) had cataract. Retinitis pigmentosa, amblyopia and age related macular degeneration (ARMD) were found in 15.32%, 15.32% and 13.13%, respectively .Figure The mean age was 41.56 ± 28.79 years (ranging from 5 to 85) in the cataract group, and the mean age of the RP group was 38.9 ± 18.89 years (ranging from 11 to 70). The mean age of the amblyopic patients was 16.81 ± 11.01 years ranging from 4 to 56, and the mean age was 69.83 ± 12.23 years ranging from 42 to 85 in the patient group having ARMD.Most of our patients had multiple causes of low vision. Nystagmus was found in highest number of patients (30.65%). Shah et al.  also fouIn a European population, Buch et al.  found myGlasses were prescribed for 107 (78.10%) patients with dioptric power ranging from +16 to −19.50. Telescopes were prescribed for 40 (29.2%) patients. Mean telescopic magnification was 3.58X . Handheld magnifiers were prescribed for 18 (13.1%) with mean power 3.06X . Closed circuit television and stand magnifier were each prescribed for a single patient. After conventional spectacles, telescopes were the most commonly prescribed optical low-vision device in this study. This is similar to the results of Kansakar et al.  and to rWe report the patients seen and devices prescribed in a low-vision clinic based in a tertiary care centre in Nepal. Most of the low-vision patients seen were of working age, and about two-thirds were under 40. More than two-thirds of the low-vision patients were male, and female low-vision patients were younger than their male counterparts. Careful refraction and adequate optical correction reduce the burden of the visual impairment. Nystagmus, high refractive error, cataract, retinitis pigmentosa, amblyopia and ARMD were the main causes of low vision. Telescopes were the major optical devices prescribed for low-vision patients.


Background and purpose — In the Netherlands about 40% of hip fractures are treated with a hemiarthroplasty (HA) or a total hip arthroplasty (THA). Although these procedures are claimed to have fewer complications than osteosynthesis , complications still occur. Analyses of data from national registries with adequate completeness of revision surgery are important to establish guidelines to diminish the risk for revision. We identified risk factors for revision.Patients and methods — All patients older than 50 years of age with a hip fracture treated with arthroplasty by orthopedic surgeons and registered in the  Dutch arthroplasty register (LROI) were included in the study. In this register, patient characteristics and surgical details were prospectively collected. Revision surgery and reasons for revision were evaluated. A proportional hazard ratio model for revision was created using competing risk analysis (with death as competing risk).Results — 1-year revision rate of HA was (cumulative incidence function [CIF] 1.6% (95% CI 1.4–1.8) and THA 2.4% (CI 2.0–2.7). Dislocation was the most common reason for revision in both groups . Male sex, age under 80 years, posterolateral approach, and uncemented stem fixation were risk factors for revision in both THA and HA. THA patients with ASA classification III/IV were revised more often, whereas revision in the HA cohort was performed more often in ASA I/II patients.Interpretation — After arthroplasty of hip fractures, both a posterolateral approach and an uncemented hip stem have higher risks for revision surgery compared with an anterolateral approach and an cemented stem. Arthroplasty surgery for acute hip fractures is performed in large numbers worldwide. In the Netherlands about 21,000 hip fractures occur annually  and surgical details  are prospectively registered  of 98%, and 88% for revision arthroplasty  there is a chance of potential under- or overestimation of incidence of reoperations using a Kaplan–Meier analysis  , ASA classification (I/II vs. III/IV), smoking status (yes/no), normal weight (BMI 18.5–25) was compared with overweight (BMI 25–30), type of approach , and type of stem fixation (cemented vs. uncemented). A hybrid THA was classified according to whether the stem was cemented or not, in order to be able to compare with HA. Finally, HA type of head (unipolar vs. bipolar head) was added to the analysis.The Cox model in a multivariable approach with more covariables produces hazard ratios (HR) with 95% confidence intervals (CI). The estimated coefficients of the variables were tested if they were constant with time and if time interactions were statistically significant. The variables were entered as time-varying covariables in the model when the proportional hazards assumption was violated. Separate proportional hazard models with hazard ratios (HR) are presented for HA and THA.Ethical approval was not required for this study. The Department of Orthopaedic Surgery and the Orthopaedic Research Foundation in Reinier de Graaf Hospital receive grants from Zimmer Biomet. The company (Zimmer Biomet) was not involved in this study. No conflicts of interest to declare.30,830 acute hip fractures treated with a HA or a THA were registered in the LROI database between 2007 and 2017. In 22,675 fractures a HA was performed and in 8,155 a THA. 79% received a unipolar HA, 20% a bipolar HA, and 1% a monoblock HA .Supplementary data). Revision rate was higher in THA (p < 0.001).1-year revision rate in HA was (CIF [95% CI]) 1.6% (1.4–1.8) and 5-year 2.5% (2.3–2.8). 1-year revision rate in THA was 2.4% (2.0–2.7) and 5-year 4.3% (3.8–4.8) . Dislocation, periprosthetic fracture, and infection were the most common reasons for revision. In 228 THA patients 1 reason for revision was given, in 70 patients multiple reasons (156 reasons in 70 patients). Dislocation was the most common reason for revision (41%) .Supplementary data). A proportional hazard ratio model using all significant factors showed that male sex, age below 80 years, ASA I/II, a posterolateral approach, and uncemented fixation are risk factors for revision  .In both THA and HA a fracture as a reason for revision was more common in an uncemented prosthesis  , ASA III/IV patients (35% vs. 24%), and a posterolateral approach (37% vs. 19%). A fracture was more common in older HA patients (18% vs. 9%). Infection was more common amongst male patients (23% vs. 12%) and a cemented prosthesis (21% vs. 9%).In THA dislocation as a reason for revision was more common in a cemented prosthesis (51% vs. 36%). A fracture as a reason for revision was more common in the male sex (THA 18% vs. 8%). Revision rate of THA was higher compared with the revision rate of HA. The 5-year revision rate of an HA was 2.5% and 4.3% in THA, which is in contrast to the results from randomized trials, which showed no difference between HA and THA  and THA (41%). Acetabular erosion  is a theoretical indication to perform a revision in a painful HA , probably as a result of trying to create a press-fit situation in the weaker (osteoporotic) bone . Previously the Scandinavian, British, and Australian registers have published their results . Follow-up of hip fracture patients is limited because of the high mortality rate . There are a limited number of patient characteristics registered in our national registry. Alcohol use, for instance, was not registered although it influences revision rate (Johnston and Parker In summary, revision rates in both HA and THA after an acute hip fracture are considerable. Avoidance of both an uncemented stem and a posterolateral approach may reduce the revision rate.supplementary data in the online version of this article, http://dx.doi.org/ 10.1080/17453674.2018.1499069Design of study: SM, NM, RN, AV. SM and WT did the statistical analysis. SM, NM, RN, and AV wrote the manuscript. All authors read and approved the final manuscript.Acta thanks Torben B Hansen and other anonymous reviewers for help with peer review of this study.


In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown.Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods.Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4%  of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307–1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896–944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 ) or between 31 and 365 days . Children who died had a greater incidence of malaria, 2280 [95%CI 1946–2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124–1158] per 1000 patient years in those surviving.In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.Children under-5 years old with  Plasmodium falciparum malaria are well recognized, and there is now good evidence of early morbidity and mortality associated with Plasmodium vivax infection in some endemic regions , p < 0.001). Haemoglobin concentration was recorded during the hospital presentation in 8687 (55.3%) of children and the mean haemoglobin was 8.12 g/dl [SD = 2.4]. Severe anaemia was present in 30.8% (2674/8687) of cases (Hb < 7 g/dl).At the initial presentation, 25.2% (1148/4561) of infants and 21.3%  of young children required hospitalization for treatment of their malaria. Children presenting with The first episode of malaria could be matched with pharmacy records in 92.1%  of cases. Prior to March 2006, 69.2% (2341/3385) received oral treatment with quinine or chloroquine and 23.2% (784/3385) were treated with intravenous quinine with or without an oral regimen. Following the change in policy in March 2006, 96.6%  received oral treatment with an artemisinin-based combination therapy (ACT) and 19.3%  were treated with intravenous artesunate with or without an oral regimen. In total 52.6%  of children were also prescribed primaquine (PQ), of whom 23.5% (1810) were prescribed a single dose of PQ and 70.3% (5405) were prescribed 14 day regimens; for 478 (6.2%) children, the dose of PQ could not be defined.P. vivax, but this fell to 50.4%  in young children; p < 0.0001. The incidence of malaria within 1 year was 1334 [95%CI 1307–1361] per 1000 person-years (py) in patients initially presenting with P. vivax compared to 920 [896–944] per 1000 py for those initially presenting with P. falciparum, Rate ratio 1.45 [95%CI 1.40–1.50], p < 0.001; Table Within 12 months of their first presentation 7620 (48.4%) of children had at least one re-presentation with malaria ; Fig. p < 0.001  = 1.41 [95% CI: 1.34–1.47], P. vivax were at greater risk of recurrent malaria compared to those initially infected with P. falciparum (HR = 1.48 [95%CI: 1.41–1.55]), p < 0.001); Figs. p < 0.001), admission to hospital , severe anaemia  and malnutrition . In multivariable analysis, age, ethnicity, outpatient status, species of initial infection absence of malnutrition and absence of severe anaemia remained significant risk factors for representation with malaria; Table Children initially infected with Of the 15,716 children presenting to the hospital, 266 children died within 12 months with a cumulative risk of 1.7% (95%CI: 1.5–1.9). Of these 266 deaths, 94 (35.3%) occurred within the first 7 days of the initial presentation, 35 (13.2%) between days 8 to 30, and 137 (51.5%) between days 31 and 365  and those presenting with P. falciparum infection  compared P. vivax infection .The risk of early mortality was non-significantly higher in infants (1.0% [95%CI: 0.8–1.3]) compared to young children , children initially requiring hospitalization  and those presenting with severe anaemia ; Table p = 0.003). In multivariable analysis, ethnicity, inpatient status, malnutrition and presenting with severe anaemia remained significant risk factors for early mortality; Table P. falciparum and 15.5% (15/97) in those infected with P. vivax; p = 0.437. In the 2664 (17.0%) children initially requiring admission to hospital and intravenous treatment with either quinine or artesunate, 3.4% (28/835) of those with P. vivax died within 30 days compared to 1.7% (24/1375) of those presenting with P. falciparum .Early mortality was significantly more likely in undernourished children (HR = 19.65 [95%CI: 12.86–30.04]); P. vivax, 0.8% [95%CI 0.6–1.0] in those initially presenting with P. falciparum and 1.0% [95%CI 0.6–1.6] in those with mixed infections; p = 0.34. The risk of late mortality was greater in infants than older children , children requiring admission to hospital compared to those initially managed as an outpatient , children who were undernourished  and those who were severely anaemic . Among undernourished children with malaria, the risk of late mortality was 1.2% (1/82) in those initially infected with P. falciparum and 3.9% (3/77) in those with P. vivax. In total 8% (1264/15716) of children had a recurrent episode of malaria within 30 days, of which 36.3% (459/1264) were attributable to P. falciparum, 51.1% (646/1264) due to P. vivax and 12.7% (161/1264) due to mixed infections. Children with any early recurrence of malaria had an increased risk of late mortality , which was significant following a P. vivax recurrence  but not following P. falciparum recurrence ; Fig. In total 137 (0.9%) children died between 31 and 365 days of their initial presentation. The risk of late mortality was 1.0% [95%CI 0.8–1.3] in children initially presenting with p < 0.001) and malnutrition . Whereas in the 3417 children initially admitted for the management of their malaria, independent predictors of late mortality were being an infant  and having another episode of malaria within 30 days .In the 12,065 children initially managed as outpatients, the only independent predictors of late mortality were being an infant  were malnourished, with pneumonia reported in 28.7% (37/129) and diarrhea in 19.4% (25/129). Of those 112 children with documented haemoglobin concentrations, 55 (49.1%) were severely anaemic. Of the 137 children surviving their initial episode of malaria but subsequently dying between 31 days and 1 year, 37 (27.0%) had recurrent malaria at the time of death, 47 (34.3%) were malnourished, 42 (30.7%) had pneumonia and 40 (29.2%) had diarrhea. Of the 113 children with documented haemoglobin concentrations, 47 (41.6%) were severely anaemic at the time of death. There was no significant difference in the risk of these co-morbidities between those presenting with P. vivax malaria has been documented in a range of endemic settings [P. vivax on health and survival were assessed in infants and young children in Papua Indonesia, an area co-endemic for P. vivax and P. falciparum.The acute morbidity and mortality of settings , 8, 22, P. falciparum infection were 2.3-fold more likely to be admitted to hospital for inpatient care. The 30-day risk of mortality was higher for children with P. falciparum than those with P. vivax (1.0% vs 0.7%), although this did not reach statistical significance. Conversely, the delayed risk of dying (day 31 to 365) was higher in children initially presenting with P. vivax (1.0% vs 0.8%), and by 12 months the cumulative risk of mortality was almost identical between the two species; Fig. At the acute presentation, children with P. vivax were almost 2-fold more likely to die during their hospital admission compared to those with P. falciparum and this difference remained after controlling for confounding factors. Intravenous artesunate is hypothesized to reduce the mortality of P. falciparum infection by its rapid reduction in the parasite biomass and prevention of microvascular sequestration and end organ dysfunction [We were unable to identify children fulfilling World Health Organization criteria for severe malaria since the necessary clinical and laboratory criteria were not recorded in our surveillance data (with the exception of haemoglobin). However pharmacy data were documented and allowed us to identify those who were treated with intravenous antimalarial drugs (quinine or artesunate). Intravenous artesunate was introduced for severe malaria due to any species in March 2006, and clinicians have a low threshold for prescribing this in those with clinical concern. Interestingly in patients receiving intravenous therapy, those with function . Severe function  and its function , 8. In tP. vivax to form dormant liver stages, results in the parasite relapsing weeks to months following the primary infection and this was reflected by those presenting with P. vivax being at significantly greater risk of any recurrence and multiple recurrences compared to those presenting with P. falciparum.In the current study, almost half of the children treated for malaria re-presented within 12 months with a further episode of malaria, some children experiencing up to 11 recurrences. The overall incidence of malaria after an initial episode was 1146 per 1000 py. The ability of Early parasite recurrence following discharge increased the risk of late mortality by almost 2-fold, and this effect was apparent throughout the 12 months of follow-up Fig. , suggestP. vivax infections have been shown to be at higher risk of malnutrition compared to those with P. falciparum infections [Pro-inflammatory cytokines associated with acute parasitaemia can induce anorexia and increase catabolism, and this is likely to contribute to malnutrition which has been associated with recurrent malaria –26. In tfections .P. vivax results in repeated episodes of haemolysis and dyserythropoeisis [The chronic and relapsing nature of opoeisis , 28. Wheopoeisis , 29. In P. vivax malaria was conservatively estimated at 1%, three fold higher than expected. Our study suggests that recurrent episodes of malaria may have contributed both directly and indirectly to this high mortality rate. At the time of death, only 42% of children were associated with another episode of malaria, whereas, 28% were malnourished, 45.3% had severe anaemia and 55% presented with infective comorbidities such as pneumonia or diarrhea. Whilst we are unable to discern the proportion of deaths directly attributable to recurrent episodes of malaria, our findings suggest that the management of acute malaria must include both acute treatment of peripheral parasitaemia, malnutrition and severe anaemia, as well as interventions to prevent subsequent malaria recurrence, such as insecticide treated bednets, prophylaxis or radical cure. The latter requires administration of a combination of a blood schizontocidal drug with a hypnozoitocidal agent. The only currently available drug that targets the dormant liver stage is primaquine, an 8-aminoquinoline compound, which can cause severe heamolysis in G6PD deficient individuals. Concerns over its potential toxicity have limited its use in young children. The World Health Organization recommends that in areas where G6PD testing is unavailable, the use of primaquine should be based on careful assessment of risk and benefit of the treatment [The under-five mortality rate in at the RSMM hospital, during the study period, was 61 per 1000 live births, with 72% of deaths occurring within the first 7 days of life (unpublished data). Hence in babies surviving the neonatal period, the overall risk of dying was approximately 0.3% per year. In the current analysis the corresponding risk of mortality in young children presenting with reatment . Our finThis study has several important limitations. Firstly, the medical records collected included limited clinical data and relied upon the diagnosis made by the attending physician, coded according to the International Classifications of the Disease 10 (ICD-10). The diagnosis of severe malaria was not captured, however, patients with severe malaria would be more likely to be admitted and be treated with intravenous antimalarials. We assumed that all deaths from severe malaria would have occurred within 31 days. In a previous study at the same location, we showed the important contribution of sepsis and co-morbidities to malaria attributable mortality . Since oP. falciparum versus those presenting with P. vivax. Previous community surveys have shown that patients with malaria due to either P. falciparum or P. vivax have a similar tendency to seek medical attention at the same location and in this region, a high proportion of deaths in young children occur at RSMM hospital [This study was limited to patients attending RSMM for healthcare who were mainly from one of the 7 Papuan ethnic groups, are entitled to free health services. Since we did not gather data from patients who represented at other healthcare facilities, a proportion of patients who died in the community or visited other health facilities for malaria treatment would have been missed. The primary aim of this analysis was to determine the comparative risks of recurrent malaria and death between patients initially presenting with hospital , 13. We P. vivax) in Timika.Lastly, our estimates of the comparative crude incidence of malaria in those who died versus those who survived are almost certainly biased by the development of immunity and also by differences in age. Children who die are most likely to do so before the development of effective immunity and therefore will have a greater chance of clinical malaria episodes leading up to death than those who survived. Those who died were on average younger than those who survived and it is well recognized that very young children have the highest incidence of malaria (particularly due to P. vivax and/or P. falciparum have a significant risk of representation with malaria, admission to hospital and both acute and delayed mortality. Recurrent malaria, malnutrition and anaemia were associated with an increased risk of delayed mortality. In the context of malaria elimination in Indonesia, our study suggests that focused efforts are warranted to ensure that early detection and prompt, effective treatment aimed at both eradication of the acute infection and prevention of subsequent recurrence should be delivered in this high risk population.Children under 5 years old presenting with malaria due to either


Such a facility would generate $5.5 M in average annual net income over its 30-year lifetime. Deployment of 100 such facilities in Thailand would replace all domestic production of fishmeal, 10% of world production, on ~1.5% of the land now used to cultivate oil palm. Such a global industry would generate ~$6.5 billion in annual net income.A method is described for saving 30% of the world fish catch by producing fishmeal and fish oil replacement products from marine microalgae, the natural source of proteins and oils in the marine food web. To examine the commercial aspects of such a method, we adapt a model based on results of microalgae production in Hawaii and apply it to Thailand, the world’s fourth largest producer of fishmeal. A model facility of 111 ha would produce 2,750 tonnes yr Annual production has been limited since the 1980s, when global fish catch reached maximum sustainable yield, at 5-6 million tonnes fishmeal and 1 million tonnes fish oil2.Demand has been increasing, especially as an essential ingredient in aquafeeds. Fishmeal offers a high-protein (60–65%) ingredient, with a balanced amino acid profile. Fish oil has a high level of n-3 highly unsaturated fatty acids (HUFA), which promote optimal growth and health. Prices of both commodities have more than tripled in the past 10 years. The aquaculture industry is the fastest-growing sector of food production in the world, growing at 8.8% per year from 1980 to 20103. Plant protein meals also contain anti-nutritional components which compromise digestion4. Replacements for fish oil are more problematic, as direct sources of n-3 HUFA are not produced in sufficient quantities by terrestrial plants5.The question is, where will fishmeal and fish oil come from in the future? The present supply is unsustainable. Replacements have been sought, but no satisfactory replacement products exist. The best alternate sources of protein currently available - soybean protein concentrate, wheat gluten, or corn gluten - still need to be supplemented with essential amino acids like methionine and lysine6, but the cost of production has been considered too high.The best sources of protein and oil for the diets of marine animals are marine microalgae - the very base of the marine food chain. Marine microalgae have a balanced amino acid profile, and some of them are the natural source of n-3 HUFA. Microalgae would be a commercial replacement for the highest quality fishmeal and fish oil−1 yr−1 7. The algae produced by Huntley et al.7 were separated by solvent extraction into an oil fraction for fuels and a protein-rich (63%) algae meal  used in feeding trials with shrimp and other species10; the techno-economics of a 111-ha facility, based on the production achieved, was modeled to produce fuels and feeds in the USA8.This study builds on recent advancements in large-scale algae productivity that demonstrate average yields of 78 tonnes ha11. Shrimp feed consumes more fishmeal  than any other aquafeed. Thailand now consumes ~5% of global fishmeal just for shrimp feeds. Shrimp feeds also require ~10% of the total global production of fish oil12. Production costs are lower in Thailand than in the USA, and thus greater potential exists for profitability. Finally, it makes sense to locate the source of production near the consumer as this reduces transportation and improves product freshness.To examine the commercial viability of a microalgae facility producing replacements for both fishmeal and fish oil, we reconfigure the model for Thailand, the world’s third largest exporter of farmed shrimpet al.8 and Huntley et al.7, but is located in Thailand and modified to include a total lipid extraction using ethanol and hexane13. The cultivation facility consists of a hybrid system of photobioreactors (PBR) and raceway ponds for cultivation of Desmodesmus sp. The facility includes 92 ha of sunlit cultivation area and 114,000 m3 of growth volume. Seawater is supplied from a 50-m pipeline and a gravity-based canal system typical of Thailand aquaculture (requiring 0.9 kJ/L for pumping). Unlike the design by Beal et al.8, volume transfers are accomplished by pumping rather than gravity flow (including pumping of sludge (99 MJ/d), discharge water , inoculum , and new seawater ). Nutrients are provided as ammonia and diammonium phosphate (DAP). Pure carbon dioxide (100%) is purchased as food-grade compressed gas with an uptake efficiency, defined as the amount of carbon assimilated into biomass divided by the amount of carbon supplied to the culture, of 79% in the growth volumes. The algal biomass elemental composition consists of 48% carbon, 6.3% nitrogen, and 0.6% phosphorus with a productivity of 23.8 g/m2-d7. The biomass contains 39% protein, 37% lipid, 21% carbohydrate, and 3% ash. Daily harvests are conducted with 48,000 m3 of growth volume with a modeled algal concentration of 0.46 g/L. Electricity is consumed for circulating the growth media in the PBRs and ponds, transporting carbon dioxide, mixing nutrient tanks, and seawater supply, with a total electrical input of 203 kWh/ha-d. Pond liners (reinforced polypropylene) have a 30-year life, while PBR plastic (polyethylene) is replaced every three months at a cost of $0.47/m2. The system has an effective capacity factor of 95% (347 days of operation per year).The algae production system modeled in this study Fig.  is basedet al.8 recovers 94% of the algal biomass to concentration of 20 g/L8. A filter press is used to increase concentration to 200 g/L (80% moisture) with 98% recovery efficiency and 1.1 kJ/L of electrical input.The harvesting process consists of natural settling and a filter press. The two-step settling process reported by Beal et al.13, recovering 90% of the total lipids. For each kg of algal biomass, extraction requires 1.26 L of ethanol (with 1% loss), 0.76 L of hexane (with 1% loss), 0.27 L of acetyl chloride (with 1% loss), 221 L of cooling water (with 0.1% loss), 1.5 kg of steam (with 0.1% loss), 5.6 kJ of electricity, and 1.1 kJ of heat for distillation. A ring dryer is used to further dry the recovered biomass to 95% solids, requiring 9.1 MJ/kg of algae. The facility generates 6.7 tonnes of crude lipids and 13.5 tonnes of dry algal biomass per day. The residual algae meal contains 59% protein.Lipid extraction is conducted according to the methods described by Molina Grima 14. Prices are based on current market prices in Thailand16. Greenhouse gas impacts are also sourced from ecoinvent©, version 3.2.Energy and material flows for the system are presented in Table 17 with respect to costs in the U.S. as determined previously by Beal et al.8. Labor requirements to grow and process the algae  for the facility after 30 years of operation using a cumulative discounted cash flow methodDCF), represented asThe NPV is calculated as the cumulative discounted cash flow (DCFk) associated with the facility for year k is calculated asCeq is the equity portion of the total capital cost (40%) andRtot is the annual revenue, Caop is the annual operating cost, and i is the discount rate. Annual operating costs are expressed asCE&M), land (Cland)21, maintenance (Cmtn), insurance (Cins), loan payments (Cloan), taxes (Ctax), and labor (Clabor). For each year, taxes are calculated as the product of the tax rate (t) and the difference between the net income (NI) and the losses carried forward (LF) from the previous year (if any), represented asD is depreciation and I is loan interest.The discounted cash flow  is calculated as the ratio of the energy impact of outputs  to the energy impact of inputs 14 for each material and energy flow . The system boundary includes the facility, as well as upstream impacts from material and energy flows. Waste disposal from the facility is also included. Calculating the GHG emissions per unit of algae produced and not per unit of one of the co-products  avoids the necessity of performing any controversial allocation of impacts between the two co-products.Life-cycle greenhouse gas (GHG) emissions for the production facility are calculated by applying the GHG impact from ecoinvent© database version 3.2 (IPCC 2013 methodology)2-d), lipid content (27–47%), efficiency of carbon dioxide absorption (50–95%), lipid extraction efficiency (70–95%), capacity factor (0.8–0.98), and heat for extraction (±30%).A sensitivity analysis was conducted to understand the individual effects of the main technical parameters on the economic and sustainability performances of the facility. These parameters included: productivity  to $9.5 M. From year 11–30, annual gross revenue ($10.7 M) exceeds annual costs ($4.1 M) by $6.6 M, resulting in $1.3 M of annual tax payments and a steady increase in cumulative discounted cash flow to $26.9 M. The largest contributors to the capital costs ($29.3 M) include pond liner ($8.4 M), pipes ($3.8 M), pumps ($2.8 M), ring dryer ($1.6 M), filter press ($1.2 M), extraction equipment ($1.2 M), and buildings ($1.3 M). When summing other costs over the entire 30-year facility lifetime, the largest costs include: taxes ($45.9 M), carbon dioxide ($38.6 M), PBR plastic ($15.0 M), labor ($11.1 M), electricity for circulating growth volumes ($10.7 M), heat ($8.6 M), loan interest ($8.2 M), insurance ($7.8 M), maintenance ($7.8 M), ammonia ($7.3 M), and water supply electricity ($6.3 M), for a total of $168 M. Revenues from algae oil (fish oil replacement) and residual algal biomass  over the 30-year facility life are $126 M and $197 M, respectively.2, developing longer lasting PBR plastic, implementing automated harvesting methods to reduce labor costs, eliminating pond liners, and using canals to replace pipes. As evaluated in the sensitivity and uncertainty analyses below, profit is dependent on the algal productivity and sale prices of the algae products. If aquafeed prices continue to rise, the algae replacement ingredients could fetch higher prices and generate greater profit. Conversely, if the algae products are valued at current market prices for soy oil ($0.77/kg) and soy meal ($0.30/kg) NPV is reduced to −$21.0 M after 30 years of operation. Similarly, a 50% increase or decrease in algal biomass productivity (baseline of 23.8 g/m2-d) would change the NPV to $53.4 M or −$12.7 M, respectively.The NPV could be increased by negotiating lower tax rates, obtaining low-cost or waste sources of CO24. For a very similar production system, Beal et al.25 found the EROI to range from 0.34 to 8.35 (with most probable results around 1.2) for 20 independent cases located in either Texas or Hawaii. However, that study assumed co-location with a purified stream of waste carbon dioxide and lower heating requirement for drying, which improves the EROI results as compared to this study. Similarly, Sills et al.24 show that most prior EROI assessments either assume CO2 is sourced from flue gas or exclude the upstream impacts associated with obtaining CO2. When the full energetic cost of obtaining carbon is included, the EROI is significantly reduced27.The EROI for the facility in this study is 0.69 Tables  and 2, w28, which indicates that replacing fish oil and fishmeal with algal biomass could provide significant primary energy savings. However, the terrestrial feed crops of corn and soybeans have a significantly higher EROI than the algae products in this study. Unlike algae, terrestrial crops do not require external carbon supply or continuous mixing during cultivation, and the drying requirement is much lower than for algal biomass. As a result, the superior areal productivity of algae in comparison to terrestrial crops is offset by the carbon and energy demands required for production.As shown in Fig. 2e per kg of algal biomass . Similar to the energy impacts, most GHG emissions are associated with upstream impacts for carbon dioxide  and heat produced from natural gas . The GHG emissions can be compared with soybeans, which can be considered as a reference scenario. The average GHG impact of soybeans sold on the global market, according to ecoinvent 3.2, is 3.90 kg CO2e/kg soybeans. This is comparable to the GHG emissions calculated here for microalgae. However, the global number for soybeans is an average of soybean production in several regions and GHG emissions are highly affected by deforestation rates, resulting in a wide range from 0.39 kg CO2e/kg soybean with no deforestation to 5.78 kg CO2e/kg soybean with high deforestation. The microalgae would then be environmentally competitive only if substituting soybeans produced in regions with high deforestation rates. Microalgae could be made environmentally more competitive by using electricity and heat from renewable sources, as already discussed in Beal et al.8, or by developing cultivation systems that could use flue gas from waste streams29 instead of pure carbon dioxide that requires large upstream energy inputs.As shown in Tables 2-day) that have been historically achieved in many of the existing large-scale facilities prior to the 23 g/m2-day demonstrated in Huntley et al.7 to high productivities (42 g/m2-day) that are theoretically possible but that have not yet been achieved in practice. The EROI and the GHG emissions  would produce 0.28 million tonnes yrOn a global scale, replacement of fishmeal by algae meal would need about ten times more capital and land, for a total of $30 billion and 111,000 ha. Granted that the algae facilities are not likely to all be located in Thailand, despite the modest amount of land required, we presume that enough land can be found in comparable environments – tropical locations where the cost of capital and labor are comparable to those in Thailand, or perhaps even more favorable. Global net income of $6.5 billion on sales of $10 billion await players in this new industry, which is poised to grow quickly.31.Algae production is a far more sustainable industry than continuing to harvest 30% of the world fish catch for fishmeal and fish oil at ever-increasing cost. The release in fishing pressure could have a dramatically favorable effect on marine ecosystems. The fishes that are caught for rendering into fish oil and fishmeal are typically small, primarily herbivorous fish such as anchovies and menhaden. By not fishing for these fish we leave a huge food resource behind that fuels the production of fishes at higher trophic levels, including finfishes like tuna and salmon that are currently limited in supply. This would reverse the trend of fishing down the food web and would go a long way towards restoring sustainable global fisheriesA viable commercial technology is presented for producing marine microalgae to replace the unsustainable supply of fishmeal and fish oil. In Thailand alone, which produces about 10% of the current world supply, an investment of $3.0 billion on only 11,100 hectares, roughly 1.5% of the land now dedicated to oil palm production, would yield annual net income of $0.65 billion on sales of $1.0 billion. The global market would be ten times more profitable. If microalgae were used to replace fishmeal and fish oil globally, the effect would be to remove 30% of fishing pressure at the lower end of the food web and would contribute to a restoration of marine ecosystems.Supplementary Information


The study used a 3D digitizer to determine three-dimensional motion analysis of the 2nd cervical (C2) spinous process at end range cervical rotation with the scapula in different positions. 30 healthy adults participated in this study. Different scapula positions were adopted bilaterally and positioned passively at normal resting, depression, adduction, and abduction. Under each scapula position, bilateral end range cervical rotation and displacement of the C2 spinous process were analyzed by a 3D digitizer.Displacement of the C2 spinous process relative to the occiput was significantly correlated with range of cervical rotation under all scapular positions (p<0.05). However, there were no significant differences between end range cervical rotation and displacement of the C2 spinous process relative to the occiput in any scapular position.These results suggest that measurement of upper cervical mobility using the 3D digitizer is a reliable method that holds promise in the evaluation of people with cervical spine disorders. Neck pain has considerable impact on societal health, representing 14.6% of all musculoskeletal problems reported annually . Active Impairments in alignment of the cervical spine and scapulae are commonly cited as possible sources of pain and dysfunction –6. The sWhen assessing range of upper cervical rotation, the cervical flexion rotation test (FRT) has been recommended . In thisThe purpose of this study was to investigate the effect of different scapular positions on two parameters, namely, range of cervical rotation as well as displacement between the occiput and C2 spinous process at end range cervical rotation (C2 displacement) using the 3D digitizer device.We hypothesized that (1) range of C2 displacement would correlate with range of cervical rotation and that (2) range of C2 displacement and range of cervical rotation were both influenced by different scapular positions.Thirty healthy participants were recruited and interviewed about their medical history; none had current neck pain, systemic arthritis, systemic bone disease, neuromuscular disease, or any history of cervical surgery. All participants agreed to sign an informed consent declaration. The 30 participants were 15 males and 15 females of mean age 21.2 ± 0.8 years, mean height 166.4 ± 8.8 cm, and mean body mass 60.2 ± 9.7 kg. This study followed the Declaration of Helsinki and was approved by the Ethics Committee at the Saitama Medical University, Saitama, Japan (no. 166).In this study, with the subject seated on a bench, scapular position was bilaterally and passively set at (1) resting position, (2) depression, (3) adduction, and (4) abduction, with a neutral glenohumeral joint position. Subjects were surrounded by steel frames (Tactix™ Steel shelving Unit). Under the resting condition, subjects were in their normal relaxed seated position. Scapular depression was induced by carrying a backpack on the subject's chest containing a 6 kg weight. Scapulae adduction was achieved by a nonelastic belt securely fastened around the chest wall with both shoulder girdles extended while scapulae abduction was achieved with the same belt with both shoulder girdles flexed. A laser pointer  was strapped to the subject's head . Subjects were required to maintain the laser light in the center of a horizontal band  which was set within a height-adjustable frame. The purpose of the laser light was to enable cervical rotation without flexion or extension .μm), with the data being directly entered to modelling software  and presented graphically. As a pilot to determine accuracy and reliability of the 3D digitizer device, we analyzed 12 lengths and angles of 3 standardized accurately manufactured cubes which were guaranteed as 10.0 × 10.0 × 10.0 [mm] . As a result of this pilot study, ICC (1.1), ICC (2.1), 95%CI, and SEM (Standard Error of Measurement = SD (d) × (1-ICC) 1/2) for measuring the cube's lengths were as follows; ICC (1.2) = 0.99, 95%CI = 0.96-0.99, and SEM = 0.02 [mm], and ICC (2.1) = 0.91, 95%CI = 0.72-0.98, and SEM = 0.20 [mm]. ICC (1.2), ICC (2.1), 95%CI, and SEM for measuring the cube's angles were as follows: ICC (1.2) = 0.99, 95%CI = 0.96-0.99, and SEM = 0.14 [degrees], and ICC (2.1) = 0.99, 95%CI = 0.70-0.98, and SEM = 0.26 [degrees].The C2 spinous process, mastoid processes, and acromial angles were identified by palpation and subsequently scanned using the 3D digitizer device . Measurements were taken by manually palpating the specific bony landmarks , 95%CI, F value, and SEM [mm] were 121.3 ± 10.3 [mm], 0.96, 0.93-0.98, 79.48, and 0.11 [mm], respectively. We also analyzed the ICC (1.2), 95%CI, F value, and SEM for the distance between the C2 spinous process and the line between the 2 mastoid processes in order to confirm the absence of cervical flexion or extension at end range cervical rotation. The results were ICC (1.2) = 0.89, 95%CI = 0.82-0.94, F value = 26.12, and SEM = 2.01 [mm], respectively.Range of cervical rotation to each side was determined by the vector from the left to right mastoid process related to the vector from left to right acromial angle. C2 displacement was calculated as the change in distance between the left mastoid process and the point of intersection from a perpendicular line drawn from the C2 spinous process to a line drawn between both mastoid processes, comparing the neutral position and each end range cervical rotation position . C2 dispMuscle hardness served as a proxy for muscle tension and was determined for the levator scapulae (LS-hardness) and trapezius (TR-hardness) muscles by the muscle hardness tester . This was used to determine whether muscle hardness was influenced by end range cervical rotation and C2 displacement or not. LS-hardness was measured bilaterally at the midpoint between the C2 spinous process and the medial aspect of the spine of scapula. TR-hardness was measured bilaterally at the midpoint between the C7 spinous process and the acromial angle.All data were analyzed using SPSS Statistics (version 22.0). Correlations between C2 displacement, LS-hardness, and TR-hardness at each scapular position were calculated using Spearman correlation. Repeated-measures ANOVA with Dunnett's post hoc test were used to compare range of cervical rotation and C2 displacement with the scapula in resting position with that at 3 different scapular positions . Significant differences were set at a level of 0.05.Bilateral range of cervical rotation was significantly correlated with C2 displacement relative to the occiput in all scapula positions . These rMuscle hardness of the right LS and left and right TR with the scapulae in resting position were correlated with range of right cervical rotation. Right LS-hardness with the scapula in resting position and bilateral LS-hardness and left TR-hardness with the scapulae in adduction were correlated with range of left cervical rotation.The results of this study support our hypothesis that C2 displacement with the scapulae in resting position correlated with range of cervical rotation as we hypothesized firstly. These results are consistent with a previous study that reported that range recorded during the FRT was correlated with total range of cervical rotation . InteresAccording to previous studies, it has been reported that scapular depression may contribute to prolonged compressive loading of the cervical spine through the cervicoscapular muscles such as upper TR and LS . SimilarIt has been proposed that scapular depression might be a contributing factor in neck pain , and scaClinically, upper cervical rotation is impaired in people with cervicogenic headache (CGH) . The latSeveral limitations need to be noted with regard to the study findings. Firstly, C2 displacement in mm cannot be directly related to the angle of rotation in degrees. Secondly, subjects were all healthy, so it is not possible to conclude whether scapula position influences upper cervical or whole cervical rotation in people with neck pain or specific disorders such as CGH. Thirdly, the relationship is unclear between displacement of C2 and displacement of other cervical spinous processes at end range cervical rotation in different scapular positions. Further studies should focus on C2 displacement relative to the occiput at end range cervical rotation using the 3D digitizer for the patients with neck pain, CGH, and other associated disorders.In this study, three-dimensional motion analysis of the C2 spinous process at end range cervical rotation in different scapular positions was assessed using the 3D digitizer device. C2 displacement relative to the occiput was significantly correlated with range of cervical rotation under all scapular positions. Despite this finding, there were no significant differences in range of cervical rotation and displacement of C2 spinous process relative to the occiput in any scapular position. These results suggest that measurement of upper cervical mobility using the 3D digitizer is a reliable method that holds promise in the evaluation of people with cervical spine disorders. Future studies should verify the measurement of 3D digitizer determined C2 displacement before acceptance of this measurement method in patients with dysfunction in the upper cervical spine.


A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority , and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported.The intent-to-treat population enrolled in Japan was analyzed.N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR . LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm.Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm  contains supplementary material, which is available to authorized users. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and one of the major causes of cancer-related deaths worldwide –4. A surSorafenib is an inhibitor of multiple protein kinases, including the serine-threonine kinase Raf-1 and tyrosine kinase, vascular endothelial growth factor (VEGF) receptors, and platelet-derived growth factor (PDGF) receptors. This oral medication acts as an antiangiogenic and was shown to be effective for the treatment of patients with unresectable HCC in the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial  and in tLenvatinib is a novel antiangiogenic, orally acting multikinase inhibitor that targets VEGF receptors 1–3, fibroblast growth factor receptors 1–4, PDGF receptor-α, and RET and KIT proto-oncogene products , 18. WitGiven the observations from these trials, a phase 3, multicenter, randomized, open-label, non-inferiority trial was conducted to compare the efficacy and safety of lenvatinib and sorafenib in first-line therapy for patients with unresectable HCC (REFLECT) , 291 , ECOG PS (0 or 1), and body weight (<60 kg or ≥ 60 kg).Patients received oral lenvatinib 12 mg/day (for ≥ 60 kg body weight) or 8 mg/day (for < 60 kg body weight) , 28 or sTumors were examined by local investigators in accordance with mRECIST for HCC, and mRECIST- and RECIST 1.1-based tumor evaluations , 26 werePharmacokinetic parameters were derived by a population pharmacokinetic analysis for lenvatinib .The primary efficacy endpoint (OS), secondary endpoints , and the details of the statistical analysis approach for the endpoints were described previously .Safety information was collected throughout the study, and any adverse events (AEs) reported were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 .All Japanese subset analyses were performed based on the intent-to-treat population enrolled in Japan. Kaplan–Meier estimates for OS, PFS, and TTP in the two treatment arms are presented, and the differences in PFS and TTP were evaluated using the stratified log–rank test. HRs of lenvatinib vs. sorafenib and their CIs were estimated using a stratified Cox proportional hazards model. The randomization stratification factors were considered as strata. The ORR difference was evaluated using the Cochran–Mantel–Haenszel Chi-square test with randomization stratification factors as strata, and with associated odds ratio (OR) and 95% CI. No multiplicity adjustments were made.All statistical analyses were performed using SAS version 9.3.Of the 954 eligible patients randomized to either arm in the REFLECT study , 168 JapP = 0.0104; Fig. P = 0.0087). Significant improvement with lenvatinib vs. sorafenib was shown in the ORR (CR + PR), 29.6% vs. 6.9%, with an odds ratio [OR] (95% CI) of 7.03 . One patient in each of the lenvatinib and sorafenib arms had a complete response (CR), and the partial response (PR) rate was several-fold higher in the lenvatinib arm (28.4%) than in the sorafenib arm (5.7%). The disease control rate  was 79.0% vs. 60.9%, with an OR of 2.42   was 17.6 12.2–23.0) months in the lenvatinib arm and 17.8 (11.9–19.5) months in the sorafenib arm, with an HR (95% CI) of 0.90 (0.62–1.29)  (Table S2). AEs and ADRs of grade 3 or higher occurred with similar incidence in the two arms. While the median treatment duration was longer for lenvatinib than for sorafenib (5.7 vs. 3.7 months), adjustment by patient-years  gave simThe mean dose intensities of lenvatinib were 6.3 mg/day and 8.5 mg/day in the patients with starting doses of 8 mg and 12 mg, respectively. The mean dose intensity of sorafenib was 558.1 mg/day. Study drugs were reduced, interrupted or discontinued due to ADR occurrence in 61.7% and 59.8%, 56.8% and 46.0%, and 11.1% and 12.6% of lenvatinib-treated patients and of sorafenib-treated patients, respectively. The median time to first dose reduction was 9.9 weeks for lenvatinib and 3.0 weeks for sorafenib.Following completion/termination of treatment with the trial medications, more than 70% of Japanese patients received post-study anticancer medications and/or procedures in each arm during the survival follow-up period (Table S3). Of the subsequent anticancer medications received by the Japanese patients, sorafenib was used most frequently in both arms (45.7% and 27.6%), followed by antimetabolites (11.1% and 18.4%). Approximately 60% of the Japanese patients underwent post-study anticancer procedures. Commonly performed anticancer procedures were similar in the two arms, including transarterial (chemo) embolization (40% and 44%), followed by hepatic intra-arterial chemotherapy (25% and 24%).According to the body weight-based dosing recommendation , JapanesThe multinational, phase 3 REFLECT study provided the results of lenvatinib use in patients with unresectable HCC, showing an effect on OS compared to sorafenib that was statistically confirmed by non-inferiority , 29. TheThe median OS (95% CI) was 17.6 (12.2–23.0) months in the lenvatinib arm vs. 17.8 (11.9–19.5) months in the sorafenib arm of the Japanese subset, giving an HR (95% CI) of lenvatinib vs. sorafenib of 0.90 (0.62–1.29), which was comparable to 0.92 (0.79–1.06) obtained for the overall population . The poiIn Japan, a nationwide HCC surveillance program has been conducted for decades, encouraging patients to consult their physicians and hence to receive appropriate medications and procedures for HCC treatment at an earlier disease stage. In addition, a high proportion of the Japanese patients compared to the overall population received anticancer medications (49.4% vs. 32.6% in the lenvatinib arm and 49.4% vs. 38.7% in the sorafenib arm) and/or underwent anticancer procedures (55.6% vs. 25.5% and 63.2% vs. 27.3%) during the survival follow-up period after completion or termination of the study treatment. Thus, the long-term surveillance activities and therapeutic improvements achieved in-between have presumably led to the survival as longer OS observed in Japanese patients following lenvatinib (or sorafenib) use than in the overall population , 38.The secondary endpoints including PFS, TTP, and ORR were improved with clinical significance in the Japanese population, when lenvatinib was compared with sorafenib. Similar observations were noted in the overall population .Despite such benefits of lenvatinib use over sorafenib use, there was no significant difference in OS between the two Japanese arms, as observed in the overall population . This maThe median treatment duration was longer in the lenvatinib arm than in the sorafenib arm. Despite this, the total incidence of AEs and ADRs and the incidence of AEs and ADRs of grade 3 or higher were similar in the two treatment arms in the Japanese subset. Hypertension was reported at a higher incidence rate in the Japanese subset than in the overall population in both arms . The meaWhile the mean dose intensity of lenvatinib was lower in the Japanese subset than in the overall population , the proportion of patients who experienced dose reduction and interruption of the drug was higher in the Japanese subset , likely due to the higher frequency of certain ADRs. However, the frequency of discontinuations due to ADRs was comparable (11% vs. 9%), suggesting that the ADRs were generally manageable despite their frequent occurrence. In the phase 2 trial, which recruited mostly (>90%) Japanese patients, the starting dose of lenvatinib was set at 12 mg, and 22% of the patients discontinued the trial due to ADRs . The lowTo achieve appropriate ADR management during lenvatinib use, it is important to assess the individual patients prior to the start of treatment for a high risk of developing ADRs and to take appropriate actions, such as dose reduction, dose interruption, and/or supportive therapy to maintain the highest possible dose intensity as high as possible. These measures enable optimization of lenvatinib treatment , 39.In conclusion, a subset analysis of the REFLECT study clearly demonstrated meaningful clinical improvements in PFS and ORR with lenvatinib over sorafenib for the treatment of Japanese patients with HCC. Careful management of AEs is required in clinical practice for long-term use of lenvatinib. Overall, the results presented here provide a basis for lenvatinib use as a first-line therapy, expanding treatment options for Japanese patients with unresectable HCC.Supplementary file1 (DOCX 37 kb)Below is the link to the electronic supplementary material.


Variability among manufacturers of urine dipsticks, respective to their accuracy and measurement range, may lead to diagnostic errors and thus create a serious risk for the patient. Our aims were to determine the level of agreement between 12 most commonly used urine dipsticks in Croatia, examine their accuracy for glucose and total protein and to test their repeatability.A total of 75 urine samples were used to examine comparability and accuracy of 12 dipstick brands . Agreement between each dipstick and the reference (Combur 10 TestM) was expressed as kappa coefficient (acceptable κ ≥ 0.80). Accuracy for glucose and total protein was tested by comparison with quantitative measurements on analysers: AU400 , Cobas 6000 c501  and Architect plus c4000 . Repeatability was assessed on 20 replicates (acceptable > 90%).Best agreement was achieved for glucose, total protein and nitrite  and the lowest for bilirubin . Sensitivities for total protein were 41-75% (AU400) and 56-92% (Cobas and Architect); while specificities were 41-75% . Dipsticks’ sensitivity and specificity for glucose were 68-98%. Most of the dipsticks showed unacceptable repeatability  for one parameter, most prominently for pH .Most commonly used dipsticks in Croatia showed low level of agreement between each other. Moreover, their repeatability varies among manufacturers and their accuracy for glucose and proteins is poor. Urine dipstick analysis is one of the most commonly performed tests in clinical laboratories. It is a simple and rapid test suitable for emergency as well as for primary care settings where urine dipstick analysis is often used to diagnose urinary tract infections, proteinuria, haematuria, and some other conditions  perform urine dipstick testing. Based on the data of our national External Quality Assessment (EQA) provider , there are 14 urine dipstick manufacturers on the market, who all together offer 24 different types of urine dipsticks . Our hypothesis was that dipsticks used for qualitative urinalysis in Croatia are heterogeneous and poorly standardized. Although many authors have studied the comparability of several dipsticks, such a comprehensive analysis of 12 different dipstick manufacturers so far has not been done. Our aim was therefore: a) to determine the level of agreement between 12 most commonly used dipsticks in Croatia using urine samples, and b) to examine their analytical performance by determining their repeatability and analytical accuracy for glucose and total protein .This analytical validation study was done in the University Hospital “Sveti Duh”  between March and May 2017. We have collected 75 urine samples from in- and out- patients to validate comparability and accuracy of 12 dipstick brands used in Croatia. Samples were collected randomly (at any time) in polystyrene tubes  and analysed within 2 hours of sample receipt. Additionally, 12 urine samples were used to validate repeatability for each dipstick brand. The list of 12 dipsticks used in this study is provided in Urine samples were carefully chosen according to the results  obtained on automated urinalysis chemistry analyser  to ensure a wide range of concentrations of each dipstick parameter. Only urine samples with adequate volume (at least 5 mL) have been selected and further divided into three aliquots (1 mL each) and the rest of the sample was used for urine test strips dipping. Aliquotes were measured on three automated analysers to assess dipsticks accuracy for glucose and total protein. Patient data privacy was ensured throughout the study. Study was done with the approval of the hospital Ethical Committee.Comparability and repeatability of the dipsticks were performed according to the Clinical and Laboratory Standards Institute (CLSI) guideline EP12-A2 (e.g. the same room temperature and light exposure). Three observers also visually examined these dipsticks.Dipsticks repeatability was tested on 20 repeated measurements of each dipstick brand. Replicates were done using the same urine sample in one laboratory  separately  in 20 days. Day-to-day precision performance criteria  were set in accordance with Reference Institute for Bioanalytics (RfB): for proteins 19.73% and 10.13% (at concentrations 0.15 and 0.97 g/L) and for glucose 10.94% and 7.81% (at concentrations 1.2 and 11 mmol/L).Level of agreement between each dipstick and the reference dipstick was tested by weighted kappa test and expressed as Cohen kappa value (κ). The most commonly used brand in Croatia in 2017 , served as a reference. Kappa value was considered acceptable if ≥ 0.80 , Combur 10 Test UX (Roche), ComboStik 10M , ComboStik 11M , Combina 10M (Human) and Multistix 10SG (Siemens) for bilirubin and UriGnost 11 (BioGnost Ltd.) for erythrocytes.Analytical accuracy of urine dipsticks for glucose and total protein was assessed by comparing the readings from the dipsticks with the true value of the parameter measured by the quantitative test results from chemistry analysers. Glucose and total protein concentrations were distributed into categories: for total protein: N = 0 - 0.29 g/L, 1 = 0.30 - 0.99 g/L, 2 = 1.00 - 2.99 g/L, 3 = more than 3.00 g/L); and for glucose: N = 0 - 2.79 mmol/L, 1 = 2.80 - 8.29 mmol/L, 2 = 8.30 - 27.99 mmol/L, 3 = more than 28 mmol/L. Categories obtained by dipstick and quantitative testing were compared and number of true positive and negative, and false positive and negative findings were established. According to these results, analytical sensitivity and specificity were calculated for each dipstick brand. Dipsticks with sensitivity and specificity ≥ 90% were considered excellent, those with ≥ 80% were satisfactory and the other dipsticks (< 80%) were considered as being of less than acceptable quality. Acceptance criteria for repeatability was 90% (18/20 results) of repeated measurements.Data were analysed using MedCalc 12.6.2.0  statistical software.Combur 10 Test M (Roche) was chosen as a reference because it was the most commonly used dipstick brand in Croatia in 2017 according to the national EQA provider . Levels of agreement between dipsticks and the reference for each parameter, expressed as κ, are shown in The best overall comparability (κ > 0.80) was achieved for glucose and nitrite (11/11 brands) and total protein (10/11 brands). Moderate agreement (κ = 0.60 - 0.79) was observed for erythrocytes (9/10 brands) and leukocytes (9/11 brands). Overall, lowest kappa values were achieved for bilirubin. There was a weak level of agreement (κ = 0.44 - 0.54) for bilirubin in 3/5 brands and for the other two brands the agreement was minimal to none (κ = 0.33 - 0.16).Repeatability was assessed on 20 replicates of each dipstick brand . RepeataDay-to-day precision  for total protein measurement ranged 1.90 – 3.90% in the lower range (concentrations 0.18 – 0.27 g/L) and 1.10–2.88% in the higher range concentrations (0.62 – 1.26 g/L) on all three analysers. For urinary glucose measurement, CVs were 1.60 – 3.29% at lower concentrations (1.43 – 1.89 mmol/L) and 1.21 – 1.71% at higher concentrations (16.28 – 20.40 mmol/L) of control materials on all three analysers.Analytical sensitivity and specificity of each dipstick for urinary glucose measurement is presented in Analytical accuracy for urinary proteins is presented for each method  separately . RegardiAs of the analytical accuracy respective to the turbidimetric method with benzethonium chloride, Combina 10M (Human) had the highest analytical sensitivity (92%) and several other dipsticks have achieved sensitivity > 80%. However, analytical specificities for these dipsticks varied between 41 – 72%. Combina 11S (Human) had the lowest specificity for proteins (42%) and the highest false positive rate (24/75). The lowest sensitivity (56%) was observed for Combina 13 (Human), with the highest false negative rate (15/75) and only average specificity (71%).In this study, we performed comprehensive analytical verification of 12 most commonly used dipsticks in Croatia. Our results showed that these dipsticks are not sufficiently comparable and that they vary in analytical performance. Agreement between the dipsticks was acceptable for nitrites, proteins and glucose but there was remarkable diversity for other parameters like bilirubin, urobilinogen, pH and specific gravity. The most important clinically relevant finding was that most of the dipsticks did not accurately detected glucose and proteins.As previously described in the literature, quantitative methods for urinary proteins are not mutually comparable and none of the available methods is considered as a “gold standard” method . Moreover, at least for some manufacturers, low reproducibility for leukocytes might be an additional issue. Urine dipstick testing  has been proposed as a first step to diagnose urinary tract infection (UTI)  is highly necessary to minimize patient risk. We believe that, although our study addresses the situation in Croatia, it is also relevant to other countries in Europe and beyond.In summary, 12 most commonly used dipsticks in Croatia showed low level of agreement among each other. Dipsticks accuracy and precision showed considerable variability between different manufacturers. Most dipsticks do not accurately detect glucose and proteins. Given the widespread heterogeneity of available brands of dipstick manufacturers in Croatia, but also possibly even worldwide, these issues create the opportunity for patient misclassification, jeopardize patient safety and increase healthcare costs. Obviously, some improvement in that respect (


This study aimed to evaluate the characteristics of faculty and research activities of basic stem cell research groups in China.A questionnaire was administered to persons who knew the information among 46 basic stem cell research groups in China. Multiple linear regression models and repeated-measures analyses of variance were used. Repeated-measures analyses of variance were used.Of the 46 groups, 39.1% did not have any faculty recruited from abroad from 2009 to 2013, 37.0% did not have any faculty with junior-level title, 34.8% had ≤25.0% faculty with either M.D. or Ph.D. degree. Papers published in SCI journals per faculty and having faculty recruited from abroad were positively associated with research funding per faculty. The groups with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad. Repeated-measures analyses of variance showed the group with faculty recruited from abroad had significantly higher research funding per faculty over time compared with the group without faculty recruited from abroad.To increase the development of basic stem cell research, some characteristics of human resources should be improved, and the groups should recruit more faculty with overseas experience. Stem cell is one of the hottest areas in biomedical research . AlthougChinese government has provided abundant research funding to support related stem cell research . BecauseHowever, few studies have focused on the human resources and research funding and scientific papers among stem cell research groups in China by quantitative research method. Our present study was carried out with three main objectives: to describe the number and characteristics of faculty in basic stem cell research groups in China, to examine research funding and scientific papers published in science citation index (SCI) journals from 2009 to 2013 in the groups, and to explore the factors predicting research funding and scientific papers published in SCI journals from 2009 to 2013 among the groups. We hope this research will allow readers to understand the current situation of human resources, funding and scientific papers published in SCI journals among basic stem cell research groups in China.The target subjects of this study were the basic stem cell research groups in China. We researched published papers on stem cell and searched the related institutional web site. There were about 98 groups engaged in basic stem cell research in China. All the groups were invited to participate in our research. Finally, 52 groups were willing to participate in the study. The 52 groups came from 13 institutes including Peking Union Medical College, Peking University, University of Chinese Academy of Sciences, Fudan University, Shanghai Jiaotong University, Tongji University, Second Military Medical University, Zhejiang University, and other universities.A standardized questionnaire was sent to the related insiders of the 52 groups by e-mail, however, only 46 responded and completed the questionnaire thoroughly. The response rate of effective questionnaires was 88.5% (46/52).The information on the group leader included the highest level of talent programs that he got , whether the group leader was academician , whether the group leader was Ministry of Science and Technology “973 Project Chief Scientist , whether the group leader was the winner of National Science Foundation for Distinguished Young Scholars , whether the group leader was the winner of National Science Foundation for Excellent Young Scholars .The information on faculty of the basic stem cell research groups included number of faculty, numbers of faculty with different highest degree (Doctor of Medicine (M.D.) or Doctor of Philosophy (Ph.D.), Master, Bachelor), numbers of faculty with different professional title , whether had faculty recruited from abroad from 2009 to 2013 . Other information included whether the group had scientific and technological collaboration with related hospitals , whether had scientific and technological collaboration with companies , whether had scientific and technological collaboration with institutes abroad , the amount of research funding from 2009 to 2013, the number of research funding from 2009 to 2013, the number of papers published in SCI journals from 2009 to 2013.Descriptive statistical analysis was used to analyze the characteristics of the faculty of the 46 basic stem cell research groups in China. To determine the factors predicting the total amount of research funding from 2009 to 2013 and the total number of papers published in SCI journals from 2009 to 2013, multiple linear regression models with conditional stepwise analysis were used. Repeated-measures analyses of variance were used to identify changes in the amount of research funding over time between the groups with faculty recruited from abroad and the groups without faculty recruited from abroad. P<0.05 was considered significant. All data were analyzed with the SPSS 13.0 software .Informed consents were obtained from each participant. This study was approved by the Biological and Medical Ethics Committee, Second Military Medical University.Academician, Ministry of Science and Technology “973 Project Chief Scientist, National Science Foundation for Distinguished Young Scholars, National Science Foundation for Excellent Young Scholars, national talent programs or provincial and ministerial talent programs winners were defined as excellent talents. Of the 46 group leaders, 38 (82.6%) were excellent talents.Number of faculty. Number of faculty ranged from 5 to 56 (mean = 16.57±1.45) for the 46 groups.Professional title of faculty. Number of faculty with senior-level title ranged from 1 to 21 (mean = 2.87±0.53) for the 46 groups. Of the 46 project groups, 14 (30.4%) had ≤25.0% faculty with senior-level title, 21 (45.7%) had >25.0% and ≤50.0% faculty with senior-level title, 8 (17.4%) had >50.0% and ≤75.0% faculty with senior-level title, 1 (2.2%) had >75.0% and <100.0% faculty with senior-level title, 2 (4.3%) had 100.0% faculty with senior-level title. Number of faculty with middle-level title ranged from 0 to 10 (mean = 2.39±0.30) for the 46 groups. Of the 46 groups, 4 (8.7%) did not have any faculty with middle-level title. Number of faculty with junior-level title ranged from 0 to 10 (mean = 1.70±0.29) for the 46 groups. Of the 46 groups, 17 (37.0%) did not have any faculty with junior-level title  had ≤25.0% faculty with either M.D. or Ph.D. degree, 22 (47.8%) had >25.0% and ≤50.0% faculty with either M.D. or Ph.D. degree, 6 (13.0%) had >50.0% and ≤75.0% faculty with either M.D. or Ph.D. degree, 2 (4.3%) had 100.0% faculty with either M.D. or Ph.D. degree. The mean number of faculty with Master’s degree was 5.98±0.72 for the 46 groups. Of the 46 project groups, 2 (4.3%) did not have any faculty with Master’s degree, 12 (26.1%) had >0.0% and ≤25.0% faculty with Master’s degree, 24 (52.2%) had >25.0% and ≤50.0% faculty with Master’s degree, 8 (17.4%) had >50.0% and ≤75.0% faculty with Master’s degree. The mean number of faculty with Bachelor’s degree or less was 4.52±0.47 for the 46 groups. Of the 46 project groups, 4 (8.7%) did not have any faculty with Bachelor’s degree or less, 16 (34.8%) had >0.0% and ≤25.0% faculty with Bachelor’s degree or less, 23 (50.0%) had >25.0% and ≤50.0% faculty with Bachelor’s degree or less, and 3 (6.5%) had >50.0% and ≤75.0% faculty with Bachelor’s degree or less  did not have any faculty recruited from abroad from 2009 to 2013, 28 (60.9%) had faculty recruited from abroad.Of the 46 groups, 35 (76.1%) had scientific and technological collaboration with related hospitals, 30 (62.5%) had scientific and technological collaboration with related companies, and 44 (95.7%) had scientific and technological collaboration with institutes abroad.The amount of research funding from 2009 to 2013 ranged from 0 to 42.69 million RMB (mean=11.21±1.34 million RMB) for the 46 groups. The number of funded projects from 2009 to 2013 ranged from 0 to 48 (mean=9.59±1.25) for the 46 groups. Distributions regarding the number of funded projects from 2009 to 2013 were examined to be 2 (4.4%) for 0 funded projects, 15(32.6%) for 1–5 funded projects, 10 (21.7%) for 6–10 funded projects, 19 (41.3%) for ≥11 funded projects.P=.017).In Figures were generated to illustrate visually and clearly the changing trend in mean research funding per faculty from 2009 to 2013 between the group with faculty recruited from abroad and the group without faculty recruited from abroad . There wThe total number of scientific papers published in SCI journals from 2009 to 2013 ranged from 0 to 45 (mean=10.15±1.47) among the 46 groups. Of the 46 groups, 5 (10.9%) had not published any scientific papers in SCI journals from 2009 to 2013, 15 (32.6%) had published 1–5 scientific papers in SCI journals, 8 (17.4%) had published 6–10 scientific papers in SCI journals, 7 (15.2%) had published 11–15 scientific papers in SCI journals, 6 (13.0%) had published 16–20 scientific papers in SCI journals, 5 (10.9%) had published ≥21 scientific papers in SCI journals.The factors predicting the number of scientific papers published in SCI journals from 2009 to 2013 per faculty among the 46 groups are shown in Stem cell research remains a tremendously promising field of study . It contThe characteristics of faculty were also important for the development of basic stem cells research groups, such as the distributions of professional title and highest degree. Our study showed that 37.0% of the 46 groups did not have any faculty with junior-level title, 8.7% did not have any faculty with middle-level title, and 4.3% had 100.0% faculty with senior-level title. The structure of professional titles was not ideal for some of the groups engaged in basic stem cell research. The structure of professional titles should be improved for some groups.About the highest degree of faculty, our research showed that 6.5% of the 46 groups had >50.0% and ≤75.0% faculty with Bachelor’s degree or less, and 34.8% had ≤25.0% faculty with either M.D. or Ph.D. degree. Overall, 83% of the faculty had M.D. degrees, 8% had a Ph.D. degree, and 7% have both degrees . The eduThe collaboration between basic research groups and hospitals and the collaboration between basic research groups and companies could accelerate the transformation from basic research to application. Our results indicated most of the basic stem cell research groups had scientific and technological collaboration with related hospitals and companies, which was helpful to the transformation from basic stem cell research to application. Science and engineering research has become an increasingly international phenomenon. A study analyzed over 2,800 articles from the top journals that include stem cell research in their publications showed that international collaborations increased from 20.9% to 36% from 2000 to 2010 . Our resFunding had been acknowledged as one of the main drivers of scientific activities . ResearcIt was common for health and health-related professionals to study abroad. The impact of overseas experience on research capacity of Chinese health professionals indicated that the number of National Natural Science Foundation of China among the group with overseas experience was significantly higher than that among the group without overseas experience . It was The number of papers published in SCI journals from 2009 to 2013 per faculty and having faculty recruited from abroad were positively associated with the amount of research funding. To increase the development of basic stem cell research, they should be encouraged to recruit more faculty with overseas experience, especially for those groups without any faculty recruited from abroad.Ethical issues  have been completely observed by the authors.


Curdlan has been widely used as a gelling agent in various food systems. This study was performed to evaluate the rheological properties of pork myofibrillar protein (MP) with different levels of curdlan (0.5% to 1.5%) and its application to low-fat model sausages (LFS).MP mixtures were prepared with 0.5%, 1.0%, and 1.5% of curdlan. Cooking loss (%), gel strength (gf), shear stress (Pa), and scanning electron microscopy were measured. Physicochemical and textural properties of LFS containing different levels of curdlan were measured.The shear stress of MP mixtures increased with increasing levels of curdlan. MP gels with increased levels of curdlan decreased cooking loss and increased gel strength (p<0.05). The MPs with 1.0% and 1.5% of curdlan were observed more compact three-dimensional structure than those with 0.5% curdlan. Increased curdlan level in LFS affected redness (a*) and yellowness (b*) values. Although expressible moisture of LFS did not differ among curdlan levels, LFSs with various levels of curdlan decreased cooking loss as compared to control sausages. Hardness values  of LFS with 0.5% and 1.0% curdlan was increased and differ from those  of control sausages.The addition of 1.0% curdlan improved the functional and textural properties of LFS. Myofibrillar protein (MP) is composed of a variety of structural proteins including myosin, actin, tropomyosin, troponin, α-actinin, and desmin . It can Hydrocolloids including carrageenan, starch, gelatin, and xanthan can functionally improve rheological properties in the food system. They are generally used in comminuted meat products to improve emulsion stability, water/fat binding, and texture, and also can structurally interact with muscle protein. Gelatin can stabilize shrinkage and improve cooking yield due to their gelling and water binding properties . CarrageAlcaligenes faecalis var. myxogenes 10C3. Curdlan is odorless, tasteless, and colorless [Curdlan is a thermo-gel stable and water-soluble polysaccharide composed of β--linked glucosidic linkages and glucose, galactose, and mannose in an approximate molar ratio of 87.7:11.0:1.3 . It is polorless . The adholorless , which wolorless . Curdlanolorless . Finallyolorless .The previous studies reported the benefits of curdlan in meat products. However, the influence of various concentrations of curdlan on quality of meat products has not been thoroughly studied. Thus, this study carried out to determine the optimum content of curdlan on the rheological properties of pork MP gels and application to low-fat model sausages.3 cubes and stored in a –50°C freezer until untilized. Curdlan was provided by the Sncfood company .Slaughtered pork loins  on the same day were purchased from a local meat market . Visible fat and connective tissues were removed. The meat was formed into 1 to 2 cmThe frozen pork loin was thawed overnight at 4°C. The MP was adjusted to a concentration of 40 mg/mL after extraction for three times using 0.1 M NaCl in 50 mM phosphate buffer by food mixer  for 1.5 min each time. The resulting emulsion was washed with 0.1 M NaCl buffer using cheesecloth to remove connective tissue . MP, bufApproximately 3 mL of each sample mixture was loaded into the probe container of the concentric cylinder type rotational rheometer . The shear rate was increased from 0 to 300/s for 60 s. The shear rate was plotted against shear stress using Excel 2016 software . Cooking loss (CL) of MP gels heated as described above was determined as the average of five different samples and calculated as the weight before cooking compared to the weight after cooking.Gel strength of cooked MP gels was measured by Universal Testing Machine . The breaking force (gf) of five different samples was determined at a head speed of 500 mm/min by steel drill chuck . The expressed value was the average of the five determinations.3) were immersed in 2.5% glutaraldehyde (pH 7) and 0.1 M phosphate buffer solution overnight at 4°C and then in osmium tetroxide (pH 7) and 0.1 M phosphate buffer for 5 h. After rinsing three times, each sample was dehydrated by immersion for 10 min in a sequentially increasing series of ethanol solutions . Each sample was completely dried by immersion in acetone for 10 min. The dehydrated and dry samples were each gold-coated using a model 108 auto sputter coater  prior to LV-SEM microstructure examination.The three-dimensional structures of MP gels were measured by low-vacuum scanning electron microscopy (LV-SEM) . Cubed samples  followed by Duncan’s test using SPSS 20.0 statistical software at a significant level of 0.05 . A p-value <0.05 indicated a significant difference.Pork ham  was purchased for each replication from the aforementioned local market. All visible fat and connective tissue were removed and the remaining meat was ground using meat chopper . Curdlan was obtained from the aforementioned source.Model sausages were manufactured with 60% pork, 38% water, 1.3% salt, 0.4% sodium tripolyphosphate, 0.05% sodium erythorbate, 0.25% curing salt and respectively 0%, 0.5%, 1%, and 1.5% curdlan as followed by Lee and Chin study . The gro65 at an observation angle of 8°.Moisture, fat, and protein contents were measured using AOAC methods . pH was The CL (%) was calculated as the weight before cooking compared to the weight after cooking. Expressible moisture  was evaluated as previously described . SausageSausage samples (n = 10) were shaped 13 mm in height and 12.5 mm in diameter were made using a puncturing tool (12.5 mm diameter). Texture profile analysis was done using the aforementioned Instron Universal Testing Machine . Samples were compressed two times until the height was 75% of the original height. A compression probe was used with a 500 N load cell at a crosshead speed of 300 mm/min. Hardness (gf), springiness (mm), gumminess, chewiness, and cohesiveness were expressed as previously detailed .One-way ANOVA followed by Duncan’s test was done using the aforementioned SPSS 20.0 statistical software . Each experiment was performed in triplicate. A p-value <0.05 indicated a significant difference.The CL and gel strength of MP mixed gels are shown in The viscosity of MP mixtures with various levels of curdlan is shown in Microstructures of MP gels with various levels of curdlan are shown in Agrobacterium radiobacter k84 showed no differences in moisture and protein contents compared to polymer-free patties. The polymer of Agrobacterium radiobacter k84 is predominantly composed of minerals (40%) followed by carbohydrates (35%) and protein (15%) [pH and color of LFSs are shown in in (15%) . In thisin (15%)  reportedTextural properties of LFSs are shown in Although curdlan can hold water strongly among meat protein molecules, no differences in EM were observed among treatments, regardless of adding curdlan (p>0.05) . GeneralThe MP containing 1.0% and 1.5% curdlan increased the viscosity and gel strength, and CL was decreased in LFSs formulated with all three levels of curdlan. The addition of curdlan into MP or LFS resulted in a reduction in CL and therefore, curdlan improved overall quality characteristics of LFSs by retaining the water. Hardness also increased in low-fat model sausages with 0.5% and 1.0% curdlan. However, the excess addition of curdlan reduced the textural characteristics. Thus, 1.0% of curdlan is considered as an optimal level in improving the physicochemical properties of low-fat model sausages. Further study is needed to determine the mechanism of the negative effect of a high concentration (1.5%) of curdlan on LFSs.