Access to novel anti-diabetic agents in resource limited settings:A brief commentary

The prevalence of diabetes mellitus is increasing in resource limited settings.Simultaneously,there has been an increase in the number of novel therapies for the management of diabetes mellitus.However,use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings.Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes,and thus most likely to benefit from the therapy,are less likely to have negative budget impact for funders.To improve access,and reduce morbidity and mortality,requires alignment amongst key stakeholders including patient advocacy groups,health care professional councils,national departments of health,the pharmaceutical industry,treasury and finance departments.

Exclusive Fibula Osteosynthesis for Treating Open Fractures Gustillo I-III B of the Distal Half of the Leg Bones in a Resources-Limited Setting

Introduction: Management of open leg bones fractures is a challenging health issue for the surgeon, particularly true in resource-limited settings. In this study, we evaluate exclusive fibular osteosynthesis in the treatment of open fractures of the distal half of the leg bones as a therapeutic option in our context. Methods: This is a prospective, experimental, multicenter study of 30 open fractures of the distal half of the leg bones treated with exclusive fibula osteosynthesis, conducted in 3 hospitals in the DRC from January 1, 2013 to September 30, 2016. Results: The age range of 20 to 40 years grouped 22 (73.4%) patients, the sex ratio was 1:1 and the unemployed were the most involved with 16 (53.3%) cases. The Gustilo II, I, III B and III A types represented 40%, 33.3%, 20% and 6.7%, respectively. The fractures were located in the distal third in 12 (40%) cases, in the middle third in 11 (36.7%) cases, and in both malleoli in 7 cases (23.3%). Osteosynthesis of the fibula by screw plate was applied in 22 (73.3%) patients and pinning in 8 (26.7%). Satisfactory reduction of the tibial fracture site was achieved in 29 (96.7%) cases and 100% bone healing was achieved within an average of 10 weeks. Four (13.3%) loss of alignment, 1 (3.3%) infection, 1 (3.3%) skin necrosis and 2 (6.7%) ankle stiffness complicated our fractures. Conclusion: Exclusive osteosynthesis of the fibula as a common technique for fractures of the distal half of the leg bones allowed us to reduce, immobilize and consolidate the tibial fracture in the required time and to preserve the mobility of the ankle.

Pollen and Resource Limitation in Veratrum nigrum L. （Liliaceae）, an Andromonoecious Herb

Pollen limitation and resource limitation were invoked to account for the pattern that flowering plants produce more flowers and ovules than fruits and seeds. This study aimed to determine their relative importance in Veratrum nigrum, a self-compatible, perennial, andromonoecious herb. In order to determine whether female production was limited by pollen grains on stigmas or by available resources, we performed supplemental hand pollination in three populations, male-flower-bud removal in three other populations, and emasculation of hermaphroditic flowers in still another population, resulting in a total of seven populations experimentally manipulated. Across the three populations, supplemental hand pollination did not significantly increase fruit set, seed number per fruit, and total seed production per individual, nor did emasculation of hermaphroditic flowers. Taken together, our results suggest that pollen grains deposited on stigmas were abundant enough to fertilize all the ovules. Male-flower-bud removal significantly increased the mean size of hermaphroditic flowers in all three populations. Female reproductive success was increased in one population, but not in the other two populations possibly due to heavy flower/seed predation. We concluded that the female reproductive success of V. nigrum was not limited by pollen grains but by available resources, which is consistent with Bateman＇s principle. Furthermore, the female reproduction increase of male-flower-bud removal individuals might suggest a trade-off between male and female sexual functions.

Pollen and resource limitations to lifetime seed production in a wild population of the endangered plant Disanthus cercidifolius var.longipes H.T.Chang(Hamamelidaceae)

Disanthus cercidifolius Maxim.var.longipes H.T.Chang,a plant species that only occurs in a few counties in Hunan,Jiangxi and Zhejiang Provinces and with a relatively small number of individuals,is ranked as a second Class endangered species for conservation in China.We have studied the effect of pollen and resources available to female reproduction,and the reproductive mechanism of“excess flowers with low fruit set”in Disanthus cercidifolius Maxim.var.longipes H.T.Chang was discussed.Results are as follows:Pollen from different sources has significant effects on fruit set and seed set of Disanthus cercidifolius Maxim.var.longipes H.T.Chang.The pollen source rather than pollen numbers significantly affected reproduction of this species.In wild populations,producing one fruit needs about 54.8 flow-ers,and one satiation seed needs about 6.60 flowers or 83.19 ovules.After fertilizing,which was propitious to flower develop-ment,the abortion rate of flower buds was decreasing,but the flowering rate was increasing.The fruit set and seed set was also significantly increasing,while abortion rate of fruit was significantly decreasing.With the increasing percentages of cutting leaves,the fruit set decreased,but the abortion rate of fruit shows no significant differentiation among treatments.After cutting branches that were puny,broken and insect-infested branches,the flower number seemed to be decreas-ing,but the fruit set and seed set all increased significantly.After removing some flowers,the fruit set was calculated with respect to the number of flowers remaining after the treatment increased with increasing of percentages of flower removal,whereas fruit set calculated with respect to the initial number of flowers remained constant,and the mean weights of per fruit and per seed all decreased significantly.Sufficient spatial or temporal heterogeneities in nutrient levels might allow limitation of seed set by resources and pollen in a natural population,while supplying resources may indirectly affect pollination by increasing attraction of the flowers to pollinators.There were very low fruit and seed sets in natural populations of Disanthus cercidifolius Maxim.var.longipes H.T.Chang.Different factors may have interacted to effect a low fruit set.A joint adoption of the“selection abortion hypothesis”,“ovary reserve hypothesis”and“male function hypothesis”seems to be the most likely explanation for the reproductive strategy of“excess flowers with few fruit sets”in Disanthus cercidifolius Maxim.var.longipes H.T.Chang.

Management of neuroblastoma in limited-resource settings

BACKGROUND Neuroblastoma(NB)is a heterogeneous disease with variable outcomes among countries.Little is known about NB in low-and middle-income countries(LMICs).AIM The aim of this review was to evaluate regional management protocols and challenges in treating NB in paediatric oncology units in LMICs compared to high-income countries(HICs).METHODS PubMed,Global Health,Embase,SciELO,African Index Medicus and Google Scholar were searched for publications with keywords pertaining to NB,LMICs and outcomes.Only English language manuscripts and abstracts were included.A descriptive review was done,and tables illustrating the findings were constructed.RESULTS Limited information beyond single-institution experiences regarding NB outcomes in LMICs was available.The disease characteristics varied among countries for the following variables:sex,age at presentation,MYCN amplification,stage and outcome.LMICs were found to be burdened with a higher percentage of stage 4 and high-risk NB compared to HICs.Implementation of evidence-based treatment protocols was still a barrier to care.Many socioeconomic variables also influenced the diagnosis,management and followup of patients with NB.CONCLUSION Patients presented at a later age with more advanced disease in LMICs.Management was limited by the lack of resources and genetic studies for improved NB classification.Further research is needed to develop modified diagnostic and treatment protocols for LMICs in the face of limited resources.

Rationalizing Optimal Timing for Adjuvant Hormone Therapy for Patients with Breast Cancer: Impact on Limited Resource Countries

Modern day cancer chemotherapy is complex and involves multiple drugs given either sequentially or concurrently, as an adjuvant or neo-adjuvant. Besides the concentration of the drug, timing, duration and sequencing of individual drugs in combination with other similar agents play a vital role in the final therapeutic outcome. This study constitutes an exhaustive overview of current knowledge of timing and sequencing, specifically of Tamoxifen, based on tumor’s hormone receptor status, as part of a comprehensive treatment plan. It has become apparent that inappropriate timing or sequencing can be detrimental. On the other hand, appropriate timing and sequencing of Tamoxifen, based on breast cancer cell-biology, pharmacokinetics and pharmacodynamics of drugs, the body’s homeostatic response to drugs;surgery and radiation, yield huge benefit for locoregional control, long-term survival and reducing complications in patients with breast cancer. Conclusion: A rational plan for use of Tamoxifen has been recommended, based on this study;for optimal therapeutic benefit. It has also been suggested that in receptor “unknown cases”, it is beneficial to prescribe Tamoxifen, since 75% of breast cancers are likely to be estrogen receptor positive and side effects can be minimized with planned vigilance.

Gradual Bedside Reduction of Gastroschisis in a Resource Constrained Setting: Preliminary Results from 32 Cases

Introduction: Gastroschisis is one of the neonatal pathologies with bad prognosis in developing countries due to a lack of equipment. We aim to report one way of managing this malformation that could be practised everywhere, constituting an alternative approach to surgery in poor areas. Patients and Methods: This observational and descriptive study included newborn babies with gastroschisis who underwent gradual bedside reduction at the Paediatric Surgery Department of the Yaounde Central Hospital. Results: Our cohort was constituted by 32 newborn babies with a mean age of 18.12 hours on admission. The Lefort type 2 was the most frequent in 81.25% of cases. The mean time for oral feeding after complete reduction was 17.4 days and the duration of hospital stay was 24.91 days. Survival rates were at 40.63%, with a residual hernia after healing in 38.46% of cases. Conclusion: Despite the high rate of mortality, gradual reduction of gastroschisis at the bedside seems to be an opportunity for resource constrained areas and can be an alternative solution to surgery.

Dynamics and data fitting of a time-delayed SIRS hepatitis B model with psychological inhibition factor and limited medical resources

Hepatitis B is an infectious disease worthy of attention.Considering the incubation period,psychological inhibition factor,vaccine,limited medical resources and horizontal transmission,an SIRS model is proposed to describe hepatitis B transmission dynamics.In order to describe the behavior changes caused by people's psychological changes,the non-monotonic incidence rate is adopted in the model.We use the saturated treatment rate to describe the limited medical resources.Mathematical analysis shows the existence conditions of the equilibria,forward or backward bifurcation,Hopf bifurcation and the Bogdanov-Takens bifurcation.During the observation of the case data of hepatitis B in China,it is found that there are mainly three features,periodic outbreaks,aperiodic outbreaks,and periodic outbreaks turns to aperiodic outbreaks.According to the above features,we select three different representative regions,Jiangxi,Zhejiang province and Beijing,and then use our model to fit the actual monthly hepatitis B case data.The basic reproduction numbers that we estimated are 1.7712,1.4805 and 1.4132,respectively.The results of data fitting are consistent with those of theoretical analysis.According to the sensitivity analysis of Ro,we conclude that reducing contact,increasing treatment rate,strengthening vaccination and revaccinating can effectively prevent and control the prevalence of hepatitis B.

Elbow Dislocation in Children: About Two Cases and Review of the Literature

Background: Elbow dislocations in pediatric patients are rare injuries. This is a therapeutic emergency because a delay in treatment can have disastrous consequences on the functional level of the upper limb. Objective: To present the management of elbow dislocation in children in cases of limited resources. Presentation of the Cases: These were 2 older male children aged 7 and 9 years old, admitted to the emergency room for painful functional impotence of the right elbow after a fall and landing on the right hand. Clinical and radiological examinations were in favor of posterior elbow dislocations. The reductions were carried out under sedation and immobilization in Jersey. According to Robert’s criteria, the functional result was excellent in both patients. Conclusion: Emergency reduction and immobilization whatever the means ensure an excellent functional prognosis even in cases of limited resources.

Allometric response of perennial Pennisetum centrasiaticum Tzvel to nutrient and water limitation in the Horqin Sand Land of China

Optimal partitioning theory （OPT） suggests that plants should allocate relatively more biomass to the organs that acquire the most limited resources. The assumption of this theory is that plants trade off the biomass allocation between leaves, stems and roots. However, variations in biomass allocation among plant parts can also occur as a plant grows in size. As an alternative approach, allometric biomass partitioning theory （APT） asserts that plants should trade off their biomass between roots, stems and leaves. This approach can minimize bias when comparing biomass allocation patterns by accounting for plant size in the analysis. We analyzed the biomass allo- cation strategy of perennial Pennisetum centrasiaticum Tzvel in the Horqin Sand Land of northern China by treating samples with different availabilities of soil nutrients and water, adding snow in winter and water in summer. We hypothesized that P. centrasiaticum alters its pattern of biomass allocation strategy in response to different levels of soil water content and soil nitrogen content. We used standardized major axis （SMA） to analyze the allometric rela- tionship （slope） and intercept between biomass traits （root, stem, leaf and total biomass） of nitrogen/water treat- ments. Taking plant size into consideration, no allometric relationships between different organs were significantly affected by differing soil water and soil nitrogen levels, while the biomass allocation strategy of P. centrasiaticum was affected by soil water levels, but not by soil nitrogen levels. The plasticity of roots, leaves and root/shoot ratios was ＇true＇ in response to fluctuations in soil water content, but the plasticity of stems was consistent for trade-offs between the effects of water and plant size. Plants allocated relatively more biomass to roots and less to leaves when snow was added in winter. A similar trend was observed when water was added in summer. The plasticity of roots, stems and leaves was a function of plant size, and remained unchanged in response to different soil nitrogen levels.

Federated Learning for 6G:A Survey From Perspective of Integrated Sensing,Communication and Computation

With the rapid advancements in edge computing and artificial intelligence,federated learning(FL)has gained momentum as a promising approach to collaborative data utilization across organizations and devices,while ensuring data privacy and information security.In order to further harness the energy efficiency of wireless networks,an integrated sensing,communication and computation(ISCC)framework has been proposed,which is anticipated to be a key enabler in the era of 6G networks.Although the advantages of pushing intelligence to edge devices are multi-fold,some challenges arise when incorporating FL into wireless networks under the umbrella of ISCC.This paper provides a comprehensive survey of FL,with special emphasis on the design and optimization of ISCC.We commence by introducing the background and fundamentals of FL and the ISCC framework.Subsequently,the aforementioned challenges are highlighted and the state of the art in potential solutions is reviewed.Finally,design guidelines are provided for the incorporation of FL and ISCC.Overall,this paper aims to contribute to the understanding of FL in the context of wireless networks,with a focus on the ISCC framework,and provide insights into addressing the challenges and optimizing the design for the integration of FL into future 6G networks.

Secure resource allocation against colluding eavesdropping in a user-centric cell-free massive multiple-input multiple-output system

We investigate the resource allocation problem of a cell-free massive multiple-input multiple-output system under the condition of colluding eavesdropping by multiple passive eavesdroppers.To address the problem of limited pilot resources,a scheme is proposed to allocate the pilot with the minimum pollution to users based on access point selection and optimize the pilot transmission power to improve the accuracy of channel estimation.Aiming at the secure transmission problem under a colluding eavesdropping environment by multiple passive eavesdroppers,based on the local partial zero-forcing precoding scheme,a transmission power optimization scheme is formulated to maximize the system’s minimum security spectral efficiency.Simulation results show that the proposed scheme can effectively reduce channel estimation error and improve system security.

Marginal land bioethanol production of sweet sorghum based on limited water resources in Northwest China

Sweet sorghum is considered a leading non-grain candidate for bioethanol production due to its low input requirement,good tolerance,high biomass potential,and high sugar content.However,insufficient studies have been conducted on the spatial distribution of sweet sorghum-based bioethanol production potential considering the water resources limitation.We presented a multi-factor analysis method not only considering terrain,meteorology,soil,and crop natural growth habits but also considering the local water resource to explore the available marginal land suitable for sweet sorghum cultivation and assess the bioethanol production potential in Northwest China.The results showed that 4.63×10^(7)hm^(2)available marginal land was suitable for sweet sorghum planting.Considering the constraint of local water resources,2.76×10^(6)hm^(2)available marginal land was suitable for sweet sorghum planting,accounting for 4.7%of the total available marginal land.And 1.23×10^(10)L bioethanol could be produced on it.Moreover,for these districts under low water stress levels,9.79×10^(5)hm^(2)available marginal land in Gannan Tibet AP and Longnan of Gansu and Hulun Buir of Inner Mongolia was considered a priority to develop sweet sorghum-based bioethanol,and 5.56×10^(9)L bioethanol could be produced in these districts,which can satisfy the 1.54%biofuel goal for 2050 of China.

Soft tissue coverage using pedicled flap in combat zone: A case series

Background:Soft tissue reconstruction is typically conducted after evacuation from theater of operations.If circumstances do not allow timely evacuation,however,defect site may need to be reconstructed in the combat zone.Case presentation:A total of 41 patients with extremity soft tissue defect were treated using pedicled flaps by a single orthopedic surgeon during four deployments in Chad,Afghanistan and Mali between 2010 and 2017.The mean age was 25.6 years.A total of 46 injury sites in extremities required flap coverage:19 combat-related injuries(CRIs)and 27 non-combat related injuries(NCRIs).Twenty of the injury sites were infected.Overall,63 pedicled flap transfers were carried out:15 muscle flaps,35 local fasciocutaneous flaps and 13 distant fasciocutaneous flaps.The flap types used did not differ for CRIs or NCRIs.Mean follow-up was 71 days.Complications included deep infection(n=6),flap failure(n=1)and partial flap necrosis(n=1).Limb salvage rate was 92.7%(38/41).Conclusions:Soft tissue defect can be managed with simple pedicled flaps in theatre of operations if needed.Basic reconstructive procedures should be part of the training for military orthopedic surgeons.Trial registration:Retrospectively registered in January 2019(2019-0901-001).

Reconnectable Network with Limited Resources

The reachability of a strongly connected network may be destroyed after link damage.Since many networks are directed or equivalent directed,connected by directed links with the potential for reversal. Therefore the reachability can be restored by reversing the direction of links.[1]has studied this matter under unlimited resources(transmitter and receiver)condition.In this paper the reconnectability of a net- work with limited number of receivers and transmitters is discussed.Also a linear time algorithm is given to find a reconnected reversal for limited receivers and transmitters.

Adaptation of Chinese and German maize-based food-feed-energy systems to limited phosphate resources——a new Sino-German international research training group

Phosphate is supplied to agriculture by mining and fertilizer production,followed by different steps of phosphate utilization,including primary production,feed and food consumption,and conversion of biomass,with accumulation in soils,but little recycling and severe environmental losses.Phosphate is a limited essential nutrient,however,with very uneven distribution worldwide.Closing the cycle and reducing primary phosphate consumption are fundamental future challenges.Maize has a relatively high phosphate requirement.China and Germany together cover the whole range of maize production systems.The new Sino-German international research training group"Adaptation of Chinese and German maize-based food-feed-energy systems to limited phosphate resources"(AMAIZE-P)was initiated in 2018 as a joint venture of the China Agricultural University(Beijing,China)and the University of Hohenheim(Stuttgart,Germany).The interdisciplinary and complementary research is driven by the hypothesis that under phosphate limited conditions,high productivity and high phosphate use efficiency can be achieved simultaneously by adapting phosphate cycling and availability(sources)to the multipurpose phosphate demands(sinks)in maizebased food-feed-energy systems.The educational program for doctoral researchers in China and Germany includes joint block seminars,thematic field trips,case studies,methodological courses,doctoral researchers’conferences,intercultural training sessions and personal training.

Lessons from a methanol poisoning outbreak in Egypt: Six case reports

BACKGROUND Mass methanol poisonings are challenging,especially in regions with no preparedness,management guidelines and available antidotes.CASE SUMMARY Six Ukrainian patients were referred to our emergency department in Cairo,Egypt several hours after drinking an alcoholic beverage made of 70%-ethanol disinfectant bought from a local pharmacy.All patients presented with severe metabolic acidosis and visual impairments.Two were comatose.Management was based on the clinical features and chemistry tests due to deficient resources for methanol leveling.No antidote was administered due to fomepizole unavailability and the difficulties expected to obtain ethanol and safely administer it without concentration monitoring.One patient died from multiorgan failure,another developed blindness and the four other patients rapidly improved.CONCLUSION This methanol poisoning outbreak strongly highlights the lack of safety from hazardous pharmaceuticals sold in pharmacies and limitations due to the lack of diagnostic testing,antidote availability and staff training in countries with limited-resources such as Egypt.

Effects of resource additions on species richness and ANPP in an alpine meadow community

Aims Theories based on resource additions indicate that plant species richness is mainly determined by the number of limiting resources.However,the individual effects of various limiting resources on species richness and aboveground net primary productivity(ANPP)are less well understood.Here,we analyzed potential linkages between additions of limiting resources,species loss and ANPP increase and further explored the underlying mechanisms.Methods Resources(N,P,K and water)were added in a completely randomized block design to alpine meadow plots in the Qinghai-Tibetan Plateau.Plant aboveground biomass,species composition,mean plant height and light availability were measured in each plot.Regression and analysis of variance were used to analyze the responses of these measures to the different resource-addition treatments.Important Findings Species richness decreased with increasing number of added limiting resources,suggesting that plant diversity was apparently determined by the number of limiting resources.Nitrogen was the most important limiting resource affecting species richness,whereas Pand K alone had negligible effects.The largest reduction in species richness occurred when all three elements were added in combination.Water played a different role compared with the other limiting resources.Species richness increased when water was added to the treatments with N and P or with N,P and K.The decreases in species richness after resource additions were paralleled by increases in ANPP and decreases in light penetration into the plant canopy,suggesting that increased light competitionwas responsible for the negative effects of resource additions on plant species richness.

Variation in Floral Sex Allocation and Reproductive Success in Sequentially Flowering Inflorescence of Corydalis remota var. lineariloba(Fumariaceae)

In hermaphroditic plants, female reproductive success often varies among different positions within an inflorescence. However, few studies have evaluated the relative importance of underlying causes such as pollen limitation, resource limitation or architectural effect, and few have compared male allocation. During a 2-year investigation, we found that female reproductive success of an acropetally flowering species, Corydalis remota Fisch. ex Maxim. var. lineariloba Maxim. was significantly lower in the upper late developing flowers when compared with the lower early flowers. Supplementation with outcross pollen did not improve female reproductive success of the upper flowers, while removal of the lower developing fruits significantly increased female reproductive success of the upper flowers in both years, evidencing resource limitation of the upper flowers. Female production in upper flowers was greatly improved by simultaneous pollen supplementation of the upper flowers and removal of the lower fruits, suggesting that, when resources are abundant, pollen may limit the female reproductive success of the upper flowers. The less seed mass in the upper flowers didn＇t increase in all treatments due to architecture. In the upper flowers, ovule production was significantly lower and the pollen ： ovule ratio was significantly higher. These results suggest that male-biased sex allocation in the upper flowers may lead to increased male reproductive success, whereas the lower flowers have higher female reproductive success.

Challenges in initiating antiretroviral therapy for all HIV-infected people regardless of CD4 cell count

Introduction:Recently published large randomized controlled trials,START,TEMPRANO and HPTN 052 show the clinical benefit of early initiation of antiretroviral treatment(ART)in HIV-infected persons and in reducing HIV transmission.The trials influenced the World Health Organization(WHO)decision to issue updated recommendations to prescribe ART to all individuals living with HIV,irrespective of age and CD4 cell count.Discussion:It is clear that the new 2015 WHO recommendations if followed,will change the face of the HIV epidemic and probably curb its burden over time.Implementation however,requires that health systems,especially those in low and middle-income settings,be ready to face this challenge on a large scale.HIV prevention and treatment are easy in theory yet hard in practice.The new WHO guidelines for initiation of ART regardless of CD4 cell count will lead to upfront increases in the costs of healthcare delivery as the goal is to treat all those now newly eligible for ART.Around 22 million people living with HIV qualify and will therefore require ART.Related challenges immediately follow:firstly,that everyone must be tested for HIV;secondly,that anyone who has had an HIV test should know their result and understand its significance;and,thirdly,that every person identified as HIV-positive should receive and remain on ART.The emergence of HIV drug resistant strains when treatment is started at higher CD4 cell count thresholds is a further concern as persons on HIV treatment for longer periods of time are at increased risk of intermittent medication adherence.Conclusions:The new WHO recommendations for ART are welcome,but lacking as they fail to consider meaningful solutions to the challenges inherent to implementation.They fail to incorporate actual strategies on how to disseminate and adopt these far-reaching guidelines,especially in sub-Saharan Africa,an area with weak healthcare infrastructures.Well-designed,high-quality research is needed to assess the feasibility,safety,acceptability,impact,and cost of innovations such as the universal voluntary testing and immediate treatment approaches,and broad consultation must address community,human rights,ethical,and political concerns.