Impact of Gaps in Care during Adult Care Transfer in Sickle Cell Disease

The transition from pediatric to adult health care is critical to the care of young adults with sickle cell disease (SCD). Young adults with SCD, compared with children with SCD, are at risk for a marked increase in disease severity, frequency of acute complications, healthcare utilization, and mortality. 1-4 Professional societies and healthcare experts recommend that young adults with chronic health conditions should transfer to adult-centered healthcare within 6 months of their last pediatric visit. 5-8 However, the effect of a 6-month transfer interval on healthcare utilization in SCD has not been studied. Given the complex health care needs of young adults with SCD, 9-15 it remains unclear whether the recommended 6-month transfer interval 5 is optimal. We hypothesized that longer gaps between pediatric and adult care would be associated with greater healthcare utilization in the first 2 to 6 years of adult care. This study included patients with SCD who were followed by a pediatric sickle cell program in the mid-southern US, participated in a transition to adult care program, 16 and fulfilled an initial adult visit to a partner adult SCD facility during the years 2011-2017. Participants were retrospectively followed from their first adult visit through December 31, 2017. Transfer gap was defined as the time (in months) between the last pediatric and the first adult sickle cell clinic visit. We estimated the association between varying transfer gaps from pediatric to adult care and the rate of healthcare utilization (inpatient, emergency department, and outpatient visits) in the first 2 to 6 years of adult care using negative binomial regression. Transfer gaps were evaluated at <2, ≥2 to <6, ≥6 to <9, and ≥9 months to evaluate whether adult health care utilization increased as the gap in SCD-specific care increased. Transfer gaps were also dichotomized at 6 months (>6 vs ≤6) to evaluate the current recommendation to complete transfer of patients to adult care within 6 months. 6,7 Healthcare resource utilization was analyzed for the complete follow-up (up to 6 years) and for the first 2 years of adult care to assess the immediate effects of delayed transfer. In total, 172 young adults with SCD (52% male, 63% HbSS/HbSβ 0-thalassemia) transferred to adult care at a median age of 18 years during the years 2011-2017 (Table 1). Approximately 83% of the included participants transferred to adult care within the recommended 6 months. young adults with transfer gaps ≥9 months had 2.86 (95%CI: 1.32, 6.20) times the rate of acute healthcare visits (inpatient and emergency department combined) compared to those with <2 months transfer gap (Table 2). The incidence rate ratio increased (IRR: 4.06; 95%CI: 1.65, 9.94) when evaluating the first 2 years of adult care. When evaluating the recommended transfer gap (6 months) as a dichotomous variable, those with gaps >6 months had 2.27 (95%CI: 1.18, 4.40) times the rate of acute care visits compared to those with ≤6 months transfer gap (Table 3). The incidence rate ratio increased slightly (IRR: 2.37; 95%CI: 1.29, 4.37) when evaluating the first 2 years of adult care only. There were no apparent associations between transfer gap duration and outpatient visits during the first 6 years in adult care; however, when restricted to the first 2 years of adult care, those with gaps >6 months had 1.32 (95%CI: 1.01, 1.72) times the rate of outpatient visits compared to those with gaps ≤6 months. Consistent with current guidelines, transfer gaps between pediatric and adult-centered care of greater than 6 months were found to be associated with increased acute healthcare resource utilization. Therefore, SCD transition programs would be well-served to consider policies for young adults that initiate adult care within 6 months of leaving pediatric care. Future studies should continue to investigate duration of transfer gaps from pediatric to adult care for their long-term clinical effects and explore interventions to reduce the transfer gap in the SCD population. Figure 1 Figure 1. Disclosures Shah: Novartis: Consultancy, Research Funding, Speakers Bureau; GBT: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Guidepoint Global: Consultancy; GLG: Consultancy; Emmaus: Consultancy. Hankins: Bluebird Bio: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Global Blood Therapeutics: Consultancy.

On Stability for Hybrid System under Stochastic Perturbations

The aim of this paper is to find out suitable conditions for almost surely exponential stability of communication protocols, considered for nonlinear hybrid system under stochastic perturbations. By using the Lyapunov-type function, we proved that the almost surely exponential stability remain be guaranteed as long as a bound on the maximum allowable transfer interval (MATI) is satisfied.

The effect of dilution rate and transfer interval on eco-evolutionary dynamics of experimental microbial communities

All organisms are susceptible to the environment and changing environmental conditions can infer structural modifications in predator-prey communities. A change in the environment can influence, for example, the mortality rate of both the prey and the predator, or determine how long the interaction between both partners is. This may have a substantial impact on ecological, but also evolutionary dynamics. Experimental studies, in which microbial populations are maintained by a repeated dilution into fresh conditions after a certain period of time, are able to dissipate underlying mechanisms in a controlled way. By design, dilution rate (modifying mortality) and transfer interval (determining the time of interaction) are crucial factors, but they often receive little attention in experimental design. We study data from a live predator-prey (bacteria and ciliates) system used to gain insight into eco-evolutionary principles and apply a mathematical model to predict how various dilution rates and transfer intervals would affect such an experiment. We find the ecological dynamics to be surprisingly robust for both factors. However, the evolutionary rates are expected to be affected. Our work predicts that the evolution of the anti-predator defence in the bacteria, and the evolution of the predation efficiency in the ciliates, both decrease with higher dilution rate, but increase with longer transfer intervals. Our results provide testable hypotheses for future studies of predator-prey systems and we hope this work will help improving our understanding how ecological and evolutionary processes together shape composition of microbial communities.

Mortality and coexistence time both cause changes in predator-prey co-evolutionary dynamics

All organisms are sensitive to the abiotic environment, and in multispecies communities a deteriorating environment increasing mortality and limiting coexistence time can cause ecological changes. When interaction within the community is changed this can impact co-evolutionary processes. Here we use a mathematical model to predict ecological and evolutionary changes in a simple predator-prey community under different mortality rates and times of coexistence, both controlled by various transfer volume and transfer interval. In the simulated bacteria-ciliate system, we find species densities to be surprisingly robust under changed mortality rates and times both species coexist, resulting in stable densities. Confirming a theoretical prediction however, the evolution of anti-predator defence in the bacteria and evolution of predation efficiency in ciliates relax under high mortalities and limited times both partners interact. In contrast, evolutionary trajectories intensify when global mortalities are low, and the predator-prey community has more time for close interaction. These results provide testable hypotheses for future studies of predator-prey systems and we hope this work will help to bridge the gap in our knowledge how ecological and evolutionary process together shape composition of microbial communities.

Perceptual learning evidence for an interval- and modality-invariant representation of subsecond time

A central theme in time perception research is whether subsecond timing relies on a dedicated centralized clock, or on distributed neural temporal dynamics. A fundamental constraint is the interval- and modality-specificity in perceptual learning of temporal interval discrimination (TID), which argues against a dedicated centralized clock, but is more consistent with multiple distributed mechanisms. Here we demonstrated an abstract, interval- and modality-invariant, representation of subsecond time in the brain. Participants practiced TID at a specific interval (100 ms), and received exposure to a transfer interval (200 ms), or to a different auditory/visual modality, through training of an orthogonal task. This double training enabled complete transfer of TID learning to the untrained interval, and mutual complete transfer between visual and auditory modalities. These results demonstrate an interval- and modality-invariant representation of subsecond time, which resembles a centralized clock, on top of the known distributed timing mechanisms and their readout and integration.

Pertumbuhan dan perkembangan kalus embriogenik dan embrio somatik kelapa sawit (Elaeis guineensis Jacq.) pada sistem perendaman sesaat Growth and differentiation of embryogenic callus and somatic embryos of oil palm (Elaeis guineensis Jacq.) in a temporary immersion system

SummaryIn temporary immersion system (TIS),plant materials are exposed to the medium fora short time, therefore they are more exposedto the air and a lack of oxygen frequentlyexperienced by a liquid culture can be avoided.This experiment was conducted to determinethe procedure for callus proliferation up tosomatic embryo germination of oil palm(Elaeis guineensis Jacq.) in TIS culture.Embryogenic calli of oil palm clone MK 638from Marihat Research Institute were culturedon solid medium in the dark culture room andthen used as materials for TIS. Immersion timefor all cultures was three minutes every sixhours. Callus proliferation was conducted inDF liquid culture with 5 mg/L 2,4-D and0.1 mg/L kinetin with transfer interval of 4, 6and 8 weeks. The treatments for somaticembryo maturation were kinetin and ABA,whereas for somatic embryo germination wasIBA, kinetin and GA 3 . The results show thatthe best transfer interval for callus proli-feration was four weeks. In this treatment therelative growth rate of callus was0.38 g/g/week. Somatic embryo initiation fromthe callus was done in DF mediumsupplemented with 1 mg/L 2,4-D and 0.1 mg/Lkinetin. The percentage of somatic embryowas 80% based on biomass fresh weight afterthe fourth subculture. The addition of 0.5 mg/Lkinetin and 0.05 mg/L ABA improved somaticembryo maturation of oil palm; the averagenumber of somatic embryos at advanced stages(torpedo and cotyledonary) was 16.3 embryosper flask. The addition of 2 mg/L IBA and0.5 mg/L kinetin in DF medium with half-strength macro-salt enhanced significantly thegermi-nation of somatic embryos. GA 3 at0.1 mg/L increased the total number ofgerminants.RingkasanPada sistem perendaman sesaat (SPS),bahan tanam hanya terpapar sebentar dalammedium sehingga paparan dengan udara lebihlama dan kekurangan oksigen yang seringterjadi pada kultur cair dapat diatasi. Penelitianini bertujuan menetapkan prosedur untukperbanyakan kalus embriogenik sampai denganperkecambahan embrio somatik kelapa sawit(Elaeis guineensis Jacq.) dalam kultur SPS.Kalus embriogenik kelapa sawit klon MK 638yang diperoleh dari Balai Penelitian Marihatdiperbanyak pada medium padat di ruang gelapyang kemudian digunakan sebagai bahan untukkultur cair SPS. Lama perendaman semuakultur di SPS diatur tiga menit denganfrekuensi setiap enam jam. Perbanyakan kalusdalam medium cair DF dengan 2,4-D 5 mg/Ldan kinetin 0,1 mg/L dilaksanakan denganinterval subkultur 4, 6 dan 8 minggu.Perlakuan pematangan embrio somatik adalahkinetin dan ABA sedangkan perlakuan untukperkecambahan embrio somatik adalah IBA,kinetin dan GA 3 . Hasil penelitian menunjuk-kan bahwa untuk proliferasi kalus embriogenikkelapa sawit, interval subkultur terbaik adalahempat minggu. Pada perlakuan ini laju tumbuhrelatif kalus mencapai 0,38 g/g/minggu.Inisiasi embrio somatik dari kalus dilakukanpada medium DF ditambah 2,4-D 1 mg/L dankinetin 0,1 mg/L. Persentase embrio somatikmencapai 80% dari total bobot basah biomassasetelah subkultur keempat. Penambahan kinetin0,5 mg/L dan ABA 0,05 mg/L meningkatkanpematangan embrio somatik kelapa sawit; rata-rata jumlah embrio somatik fase lanjut (torpedodan kotiledon) adalah 16,3 embrio per bejana.Penambahan IBA 2 mg/L dan kinetin 0,5 mg/Lpada medium DF dengan setengah garammakro meningkatkan perkecambahan embriosomatik secara nyata. GA 3 0,1 mg/L mening-katkan jumlah kecambah yang terbentuk.

Pertumbuhan dan perkembangan kalus embriogenik dan embrio somatik kelapa sawit (Elaeis guineensis Jacq.) pada sistem perendaman sesaat Growth and differentiation of embryogenic callus and somatic embryos of oil palm (Elaeis guineensis Jacq.) in a temporary immersion system

SummaryIn temporary immersion system (TIS),plant materials are exposed to the medium fora short time, therefore they are more exposedto the air and a lack of oxygen frequentlyexperienced by a liquid culture can be avoided.This experiment was conducted to determinethe procedure for callus proliferation up tosomatic embryo germination of oil palm(Elaeis guineensis Jacq.) in TIS culture.Embryogenic calli of oil palm clone MK 638from Marihat Research Institute were culturedon solid medium in the dark culture room andthen used as materials for TIS. Immersion timefor all cultures was three minutes every sixhours. Callus proliferation was conducted inDF liquid culture with 5 mg/L 2,4-D and0.1 mg/L kinetin with transfer interval of 4, 6and 8 weeks. The treatments for somaticembryo maturation were kinetin and ABA,whereas for somatic embryo germination wasIBA, kinetin and GA 3 . The results show thatthe best transfer interval for callus proli-feration was four weeks. In this treatment therelative growth rate of callus was0.38 g/g/week. Somatic embryo initiation fromthe callus was done in DF mediumsupplemented with 1 mg/L 2,4-D and 0.1 mg/Lkinetin. The percentage of somatic embryowas 80% based on biomass fresh weight afterthe fourth subculture. The addition of 0.5 mg/Lkinetin and 0.05 mg/L ABA improved somaticembryo maturation of oil palm; the averagenumber of somatic embryos at advanced stages(torpedo and cotyledonary) was 16.3 embryosper flask. The addition of 2 mg/L IBA and0.5 mg/L kinetin in DF medium with half-strength macro-salt enhanced significantly thegermi-nation of somatic embryos. GA 3 at0.1 mg/L increased the total number ofgerminants.RingkasanPada sistem perendaman sesaat (SPS),bahan tanam hanya terpapar sebentar dalammedium sehingga paparan dengan udara lebihlama dan kekurangan oksigen yang seringterjadi pada kultur cair dapat diatasi. Penelitianini bertujuan menetapkan prosedur untukperbanyakan kalus embriogenik sampai denganperkecambahan embrio somatik kelapa sawit(Elaeis guineensis Jacq.) dalam kultur SPS.Kalus embriogenik kelapa sawit klon MK 638yang diperoleh dari Balai Penelitian Marihatdiperbanyak pada medium padat di ruang gelapyang kemudian digunakan sebagai bahan untukkultur cair SPS. Lama perendaman semuakultur di SPS diatur tiga menit denganfrekuensi setiap enam jam. Perbanyakan kalusdalam medium cair DF dengan 2,4-D 5 mg/Ldan kinetin 0,1 mg/L dilaksanakan denganinterval subkultur 4, 6 dan 8 minggu.Perlakuan pematangan embrio somatik adalahkinetin dan ABA sedangkan perlakuan untukperkecambahan embrio somatik adalah IBA,kinetin dan GA 3 . Hasil penelitian menunjuk-kan bahwa untuk proliferasi kalus embriogenikkelapa sawit, interval subkultur terbaik adalahempat minggu. Pada perlakuan ini laju tumbuhrelatif kalus mencapai 0,38 g/g/minggu.Inisiasi embrio somatik dari kalus dilakukanpada medium DF ditambah 2,4-D 1 mg/L dankinetin 0,1 mg/L. Persentase embrio somatikmencapai 80% dari total bobot basah biomassasetelah subkultur keempat. Penambahan kinetin0,5 mg/L dan ABA 0,05 mg/L meningkatkanpematangan embrio somatik kelapa sawit; rata-rata jumlah embrio somatik fase lanjut (torpedodan kotiledon) adalah 16,3 embrio per bejana.Penambahan IBA 2 mg/L dan kinetin 0,5 mg/Lpada medium DF dengan setengah garammakro meningkatkan perkecambahan embriosomatik secara nyata. GA 3 0,1 mg/L mening-katkan jumlah kecambah yang terbentuk.