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Purpose The OPTIMISE study uses a Multiphase Optimisation Strategy (MOST) to identify the best combination of four interventions targeting key diabetes self-care behaviours for use in clinical practice to improve short-term glycaemic outcomes. Methods This 4-week intervention trial will recruit 80 young people (aged 13–20 years) with type 1 diabetes ≥ 6 months duration), and pre-enrolment HbA1c ≥ 58 mmol/mol (7.5%) in the prior 6 months. Both main intervention and interaction effects will be estimated using a linear regression model with change in glucose time-in-range (TIR; 3.9–10.0 mmol/L) as the primary outcome. Participants will be randomised to one of 16 conditions in a factorial design using four intervention components: (1) real-time continuous glucose monitoring (CGM), (2) targeted snacking education, (3) individualised sleep extension, and (4) values-guided self-care goal setting. Baseline and post-intervention glucose TIR will be assessed with blinded CGM. Changes in self-care (snacking behaviours, sleep habits and duration, and psychosocial outcomes) will be assessed at baseline and post-intervention to determine if these interventions impacted behaviour change. Discussion The study outcomes will enable the selection of effective and efficient intervention components that increase glucose TIR in young people who struggle to achieve targets for glycaemic control. The optimised intervention will be evaluated in a future randomised controlled trial and guide the planning of effective clinical interventions in adolescents and young adults living with type 1 diabetes. Trial registration This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 7 October 2020 (ACTRN12620001017910) and the World Health Organisation International Clinical Trails Registry Platform on 26 July 2020 (Universal Trial Number WHO U1111-1256-1248).

Background Both pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) significantly affect health-related quality of life (HR-QoL). We aimed to determine the impact of CPA co-infection on the HR-QoL of Ugandans with PTB. Methods We conducted a prospective study among participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda between July 2020 and June 2021. HR-QoL was assessed using St. George Respiratory Questionnaire (SGRQ) at enrollment and at the end of PTB treatment (4 months apart). SGRQ scores range from 0 to 100, with higher score representing a poorer HR-QoL. Results Of the 162 participants enrolled, 32 (19.8%) had CPA + PTB and 130 (80.2%) had PTB only. The baseline characteristics of the two groups were comparable. Regarding overall health, a higher proportion of the PTB only group rated their HR-QoL as “very good” compared to those who had both TB and CPA (68 (54.0%) versus 8 (25.8%)). At enrollment, both groups had comparable median SGRQ scores. However, at follow up, the PTB only group had statistically significantly better SGRQ scores (interquartile range); symptoms (0 (0 — 12.4) versus 14.4 (0 — 42.9), p versus 12.2 (0 — 35.5), p = .03), impact (0 (0 — 4.0) versus 3.1 (0 — 22.5), p = 0.004), and total scores ((0 (0 — 8.5) versus 7.6 (0 — 27.4), p = 0.005). Conclusion CPA co-infection impairs HR-QoL of people with PTB. Active screening and management of CPA in patients with PTB is recommended to improve HR-QoL of these individuals.

Background Adherence is key to the treatment success of multi-drug resistant tuberculosis (MDR-TB) and prevention of community transmission. Directly observed therapy (DOT) is the recommended approach for the management of patients with MDR-TB. Uganda implements a health facility-based DOT approach where all patients diagnosed with MDR-TB report to the nearest private or public health facility for daily observation of ingesting their medicines by a health care provider. Directly observed therapy is very costly for both the patient and health care system. It follows the assumption that MDR TB patients have a history of poor adherence to TB treatment. But only 21% of MDR-TB patients notified globally and 1.4–12% notified in Uganda had been previously treated for TB. The shift to all oral treatment regimen for MDR-TB provides an opportunity for the exploration of self-administered therapy for this group of patients even with use of remotely operated adherence technology. We are conducting a non-inferiority open-label randomized controlled trial to compare adherence to MDR-TB treatment among patients on self-administered therapy (measured by Medication Events Monitoring System (MEMS) technology) with a control group on DOT. Methods We plan to enrol 164 newly diagnosed MDR-TB patients aged ≥ 8 years from three regional hospitals based in rural and urban Uganda. Patients with conditions that affect their dexterity and ability to operate the MEMS-operated medicine equipment will not be eligible to participate in the trial. Patients are randomized to either of the two study arms: self-administered therapy with adherence being monitored using MEMS technology (intervention arm) or health facility-based DOT (control arm) and will be followed up monthly. Adherence is measured by the number of days the medicine bottle is open to access medication as recorded by the MEMS software in the intervention arm and treatment complaint days as recorded in the TB treatment card in the control arm. The primary outcome is the comparison of adherence rates between the two study arms. Discussion The evaluation of self-administered therapy for patients with MDR-TB is important to inform cost-effective management strategies for these patients. The approval of all oral regimens for the treatment of MDR-TB provides an opportunity for innovations such as MEMS technology to support sustainable options for MDR-TB treatment adherence support in low-resource settings. Trial registration Pan African Clinical Trials Registry, Cochrane #PACTR202205876377808. Retrospectively registered on 13 May 2022

Purpose Understanding fluxes of soil organic carbon (OC) from the terrestrial to aquatic environments is crucial to evaluate their importance within the global carbon cycle. Sediment fingerprinting (SF) is increasingly used to identify land use-specific sources of OC, and, while this approach estimates the relative contribution of different sources to OC load in waterways, the high degree of spatial heterogeneity in many river catchments makes it challenging to precisely align the source apportionment results to the landscape. In this study, we integrate OC SF source apportionment with a carbon loss model (CLM) with the aim of: (i) reducing ambiguity in apportioning OC fluxes when the same land use exists in multiple locations within a catchment; and (ii) identifying factors affecting OC delivery to streams, e.g., buffer zones. Methods Two main approaches were used in this study: (i) identification of the sources of freshwater bed sediment OC using n-alkane biomarkers and a Bayesian-based unmixing model; and (ii) modelling and analysis of spatial data to construct a CLM using a combination of soil OC content modelling, RUSLE soil erosion modelling and a connectivity index. The study was carried out using existing OC and n-alkane biomarker data from a mixed land use UK catchment. Results Sediment fingerprinting revealed that woodland was the dominant source of the OC found in the streambed fine sediment, contributing between 81 and 85% at each streambed site. In contrast, CLM predicted that arable land was likely the dominant source of OC, with negligible inputs from woodland. The areas of the greatest OC loss in the CLM were predicted to be from arable land on steeper slopes surrounding the stream channels. Results suggest extensive riparian woodland disconnected upslope eroded soil OC and, concomitantly, provided an input of woodland-derived OC to the streams. It is likely the woodland contribution to streambed OC is derived from litter and leaves rather than soil erosion. Conclusion This study demonstrates how location-specific OC sources and delivery processes can be better determined using sediment fingerprinting in combination with CLM, rather than using sediment fingerprinting alone. It highlights that, although wooded riparian buffer strips may reduce the impact of upslope, eroded soil OC on waterways, they could themselves be a source of OC to stream sediments through more direct input (e.g., organic litter or leaf debris). Characterising this direct woodland OC as a separate source within future fingerprinting studies would allow the contributions from any eroded woodland soil OC to be better estimated.

Background Blooms of marine microalgae play a pivotal role in global carbon cycling. Such blooms entail successive blooms of specialized clades of planktonic bacteria that collectively remineralize gigatons of algal biomass on a global scale. This biomass is largely composed of distinct polysaccharides, and the microbial decomposition of these polysaccharides is therefore a process of prime importance. Results In 2020, we sampled a complete biphasic spring bloom in the German Bight over a 90-day period. Bacterioplankton metagenomes from 30 time points allowed reconstruction of 251 metagenome-assembled genomes (MAGs). Corresponding metatranscriptomes highlighted 50 particularly active MAGs of the most abundant clades, including many polysaccharide degraders. Saccharide measurements together with bacterial polysaccharide utilization loci (PUL) expression data identified β-glucans (diatom laminarin) and α-glucans as the most prominent and actively metabolized dissolved polysaccharide substrates. Both substrates were consumed throughout the bloom, with α-glucan PUL expression peaking at the beginning of the second bloom phase shortly after a peak in flagellate and the nadir in bacterial total cell counts. Conclusions We show that the amounts and composition of dissolved polysaccharides, in particular abundant storage polysaccharides, have a pronounced influence on the composition of abundant bacterioplankton members during phytoplankton blooms, some of which compete for similar polysaccharide niches. We hypothesize that besides the release of algal glycans, also recycling of bacterial glycans as a result of increased bacterial cell mortality can have a significant influence on bacterioplankton composition during phytoplankton blooms.

Detrimental circumstances (e.g., poverty, homelessness) may affect parents, parenting, and children. These circumstances may lead to children being labeled "at risk" for school failure. To ameliorate this risk, more school and school earlier (e.g., Head Start) is offered. To improve child outcomes, Head Start teachers are expected to bolster children?s academic readiness in a manner that is beneficially warm, circulating warmth in their classrooms to sustain positive teacher-child relationships and the positive climate of the classroom. The Classroom Assessment Scoring System (CLASS; Pianta et al., 2008) is one tool by which these domains of warmth are assessed. There are, however, significant personal and professional stressors with which Head Start teachers contend which the CLASS (Pianta et al., 2008) does not consider in its scoring methods. Uplifting the voices of six Head Start teachers, the present study implemented individual and focus group interviews during the summer and fall months of 2020 during the COVID-19 pandemic, asking (a) What were the stories, histories, and lived experiences of these Head Start teachers with regard to stress and warmth in a time of crisis? and (b) How did these teachers understand and approach the CLASS (Pianta et al., 2008) and its measures of their warmth? Data demonstrated Head Start teachers engaged in a type of performativity to 1) mask their stress, potentially worsening their levels of stress in order to maintain warmth for their students' sake, and 2) outwit the prescribed CLASS (Pianta et al., 2008) observations. Implications and insights are discussed.The online version contains supplementary material available at 10.1007/s10643-022-01387-2.

Seafloor sediment mapping traditionally relies on the experience and expertise of practitioners to classify sediment classes based on acoustic backscatter data and ground-truth information. However, recent advancements in automated seafloor mapping present a major development in objective methods that offer practical application for seafloor mapping and monitoring campaigns. In this study, a class-specific approach of ensemble modelling (ensemble mapping) was used to classify the sediment classes of a large-scale seafloor area (1550 km2) in the western Sylt Outer Reef, German North Sea. A pixel-by-pixel comparison of the modelled map and manually digitized map was also conducted to assess the efficiency of the ensemble mapping approach. The resulting seafloor sediment map, with an overall accuracy of 73%, demonstrates five sediment classes that represent most of the seabed of the German North Sea. The manually classified and ensembled maps were 63% identical, but mismatches were observed in the transitional boundaries of soft sediment classes and in stony areas that were not predicted in manual classification. The inconsistencies between the two maps was attributed to the different interpretation of sediment boundaries, the simplification of the sediment classification scheme, and the ability of ensemble mapping to classify more areas than manual classification. This study found that ensemble mapping performs better in characterizing coarse materials and produces maps that are comparable to the maps produced by manual classification, while the production time and degree of subjectivity in the analysis are minimal. Hence, ensemble mapping is a viable alternative to create baseline seafloor sediment maps that can be used for environmental monitoring and resource planning.

PURPOSE: Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood and comes with considerable management and psychological burden for children and their families. Fear of hypoglycaemia (FOH), particularly nocturnal hypoglycaemia, is a common worry. Continuous glucose monitoring (CGM) is a tool that may help reduce FOH, as well as reduce overall diabetes burden. However, CGM systems are expensive and often not publicly funded or subsidised. MiaoMiao (MM) is a novel relatively affordable third-party add-on technology to intermittently scanned CGM (isCGM). MM allows users to convert their isCGM to a form of “Do-it-yourself” (DIY)-CGM. Our hypothesis is that MM-CGM will result in significant reduction in parental fear from hypoglycaemia. The primary objective is to determine the impact of real-time DIY-CGM on parental fear of hypoglycaemia using Hypoglycaemia Fear Survey (HFS). METHODS: This is a multisite randomised cross-over study of 55 New Zealand children (ages 2–13 years) with established T1D and current users of isCGM (Abbott FreeStyle Libre). DIY-CGM will be compared to usual care with isCGM. Participants will be randomised to either arm of the study for 6 weeks followed by a 4-week wash-out period before crossing over to the other study arm for a further 6 weeks. DISCUSSION: The results of this study will provide much needed clinical trial data regarding DIY-CGM effectiveness in reducing parental FOH, as measured by HFS, as well as various other secondary outcomes including traditional glycaemic metrics, and child and caregiver sleep. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12619001551189) on 18 November 2019, and the World Health Organisation International Clinical Trial Registry Platform (Universal Trial Number U1111–1236-9189).

Although strategies to prevent premature sensor loss for flash glucose monitoring (FGM) systems may have substantial benefit, limited data are available. This study among youth with high-risk type 1 diabetes evaluated whether an additional adhesive patch over FGM sensors would reduce premature sensor loss frequency and not cause additional cutaneous adverse events (AEs). This is a six-month, open-label, randomized crossover trial. Participants were recruited at completion of prior ‘Managing Diabetes in a Flash’ randomized controlled trial and allocated to three months of Freestyle Libre FGM sensors with either standard adhesive (control) or additional adhesive patches (RockaDex, New Zealand) (intervention), before crossing over to the opposite study arm. Participants self-reported patch use or non-use, premature sensor loss and cutaneous AEs fortnightly via an electronic questionnaire. Thirty-four participants were enrolled: mean age (± SD) 17.0 (± 2.2) years; mean HbA1c (± SD) 89 (± 16) mmol/mol (10.3% ± 1.4%). The response rate of questionnaires was 77% (314/408). Premature sensor loss was reported in 18% (58/314) of questionnaires: 20% (32/162) from intervention and 17% (26/152) from control (p = 0.56). Thirty-eight percent (118/314) of questionnaires were non-compliant to protocol allocation. However, per-protocol analysis showed similar findings. No significant difference in AEs was reported between compliant adhesive patch use and non-use (6% [5/78] and 3% [3/118], respectively, p = 0.27). The adhesive patch investigated in this study does not appear to prevent premature FGM sensor loss. However, the low risk of AEs and low cost of an adhesive patch suggest an individualized approach to their use may still be warranted. Further research is needed to explore alternative strategies to prevent sensor loss.

Global change puts coastal marine systems under pressure, affecting community structure and functioning. Here, we conducted a mesocosm experiment with an integrated multiple driver design to assess the impact of future global change scenarios on plankton, a key component of marine food webs. The experimental treatments were based on the RCP 6.0 and 8.5 scenarios developed by the IPCC, which were Extended (ERCP) to integrate the future predicted changing nutrient inputs into coastal waters. We show that simultaneous influence of warming, acidification, and increased N:P ratios alter plankton dynamics, favours smaller phytoplankton species, benefits microzooplankton, and impairs mesozooplankton. We observed that future environmental conditions may lead to the rise of Emiliania huxleyi and demise of Noctiluca scintillans, key species for coastal planktonic food webs. In this study, we identified a tipping point between ERCP 6.0 and ERCP 8.5 scenarios, beyond which alterations of food web structure and dynamics are substantial.

Background In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

Background Communities affected by infectious disease outbreaks are increasingly recognised as partners with a significant role to play during public health emergencies. This paper reports on a qualitative case study of the interactions between affected communities and public health institutions prior to, during, and after two emerging tick-borne disease events in 2016: Crimean-Congo Haemorrhagic Fever in Spain, and Tick-Borne Encephalitis in the Netherlands. The aim of the paper is to identify pre-existing and emergent synergies between communities and authorities, and to highlight areas where synergies could be facilitated and enhanced in future outbreaks. Methods Documentary material provided background for a set of semi-structured interviews with experts working in both health and relevant non-health official institutions (13 and 21 individuals respectively in Spain and the Netherlands), and focus group discussions with representatives of affected communities (15 and 10 individuals respectively). Data from all sources were combined and analysed thematically, initially independently for each country and then for both countries together. Results Strong synergies were identified in tick surveillance activities in both countries, and the value of pre-existing networks of interest groups for preparedness and response activities was recognised. However, authorities also noted that there were hard-to-reach and potentially vulnerable groups, such as hikers, foreign tourists, and volunteers working in green areas. While the general population received preventive information about the two events, risk communication or other community engagement efforts were not seen as necessary specifically for these sub-groups. Post-event evaluations of community engagement activities during the two events were limited, so lessons learned were not well documented. Conclusions A set of good practices emerged from this study, that could be applied in these and other settings. They included the potential value of conducting stakeholder analyses of community actors with a stake in tick-borne or other zoonotic diseases; of utilising pre-existing stakeholder networks for information dissemination; and of monitoring community perceptions of any public health incident, including through social media. Efforts in the two countries to build on the community engagement activities that are already in place could contribute to better preparedness planning and more efficient and timely responses in future outbreaks.

Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.

It is well known in contemporary Madhyamaka studies that the seventh century Indian philosopher Candrakīrti rejects the foundationalist Abhidharma epistemology. The question that is still open to debate is: Does Candrakīrti offer any alternative Madhyamaka epistemology? One possible way of addressing this question is to find out what Candrakīrti says about the nature of buddha’s epistemic processes. We know that Candrakīrti has made some puzzling remarks on that score. On the one hand, he claims buddha is the pramāṇabhūta-puruṣa (person of epistemic and moral authority), sarvākārajnatājnānaṃ (omniscient, wise), pratyakṣalakṣaṇam (exclusively perceptual in characteristic) [Candrakīrti (MABh VI.214)], and claims that there are clearly four pramāṇas—epistemic warrants—direct perception (pratyakṣa), inference (anumāna), testimony (āgama) and analogy (upamāna) [Candrakīrti (Pp I.3), cf. MacDonald 2015, pp. 287–288]. On the other hand, somewhat paradoxically, Candrakīrti claims that buddhahood is an embodiment of a complete cessation of “mind and mental processes” [Candrakīrti (MABh XI.1, 155a; MAB XI.17d)] Now how are we to make sense of these two seemingly contradictory statements? Do these statements reflect any deeper conflicts within Candrakīrti’s system or is there a coherent way to interpret these statements? The Tibetan Prāsaṅgika interpreters of Candrakīrti’s Madhyamaka largely agree that there is no internal contradiction in Candrakīrti’s system, and agree there is a way to make coherent sense of these statements. Nevertheless, the Tibetans exegetes bring to the table two radically conflicting proposals to approach Candrakīrti’s Mādhyamaka; both claiming to successfully address the apparent tension arising from Candrakīrti’s statements. One proposal is made by Tsongkhapa Losang Dakpa (Tsong kha pa bLo bzang grags pa, 1357–1419), who maintains the tension can be plausibly resolved by demonstrating that Candrakīrti’s unique non-foundationalist epistemological program renders him an epistemological coherentist. In contrast Taktsang Lotsawa Sherap Rinchen (sTag tshang Lo tsā ba Shes rab rin chen, 1405–1477) argues that according to Candrakīrti buddha is a global agnostic, on the ground of the nonexistence of mind and mental processes for those who have attained fully awakening. Taktsang instead proposes the no-mind thesis as a more plausible way to resolve the tension in Candrakīrti’s philosophy, categorically refusing to attribute to buddha any cognitive processes and epistemic warrants. This paper is an analysis of Taktsang’s no-mind thesis—the claim that buddhas utterly lack any knowledge of the world because they do not have epistemic processes and warrants to perceive the world—in what follows a rational reconstruction of his arguments is developed in order to evaluate his thesis. We shall then assess the implications of accepting Taktsang’s no-mind thesis.

PURPOSE: Worldwide, the use of insulin pumps for the management of type 1 diabetes is increasing. There are no national or international published guidelines and few guidance recommendations detailing the education and training required to commence insulin pump therapy. The aim of this study is to describe current clinical practice regarding initiation of insulin pump therapy in children and adolescents with type 1 diabetes in New Zealand. METHODS: Pediatric diabetes nurse specialists from selected New Zealand hospitals (n = 16) were identified and invited to participate in this qualitative study. For those consenting, structured interviews were conducted. The questions covered basic hospital demographics and various aspects of insulin pump initiation including pump start planning, education, and aspects of follow-up and after-care. RESULTS: The response rate was 100% (16 out of 16 hospitals). Diabetes clinics interviewed varied in size from 50 to 450 pediatric patients and frequency of insulin pump use from 11% - 46%. Clinical practice differed between clinics. Important differences related to: use of continuous glucose monitoring (12/16); and differing views on immediate vs. delayed use of pump advanced features. Location of pump starts also varied, with both in-patient (2/16) and out-patient (14/16) approaches seen. The motivations and beliefs relating to these various pump start approaches also varied. CONCLUSIONS: Differences seen between hospitals reflected team preference, and possibly a lack of consensus/guidance from the medical literature. Lessons may be learnt and further rationalisation and improvement in education remains possible by combining and adopting strengths from different hospitals.

Background Throughout the last decade, tuberculosis (TB) treatment success has not surpassed 90%, the global target. The impact of mobile health interventions (MHIs) on TB treatment outcomes is unknown, especially in low- and middle-income countries (LMICs). MHIs, including interactive voice response technology (IVRT), may enhance adherence and retention in the care of patients with tuberculosis and improve TB treatment outcomes. This study seeks to determine the impact of IVRT-based MHI on TB treatment success (treatment completion and cure rates) in patients with TB receiving care at five public health facilities in Uganda. Methods We used a theory-based and human-centered design (HCD) to adapt an already piloted software to design “Call for life-TB” (CFL-TB), an MHI that utilizes IVRT to deliver adherence and appointment reminders and allows remote symptom reporting. This open-label, multicenter, randomized controlled trial (RCT), with nested qualitative and economic evaluation studies, will determine the impact of CFL-TB on TB treatment success in patients with drug-susceptible TB in Uganda. Participants (n = 274) at the five study sites will be randomized (1:1 ratio) to either control (standard of care) or intervention (adherence and appointment reminders, and health tips) arms. Multivariable regression models will be used to compare treatment success, adherence to treatment and clinic appointments, and treatment completion at 6 months post-enrolment. Additionally, we will determine the cost-effectiveness, acceptability, and perceptions of stakeholders. The study received national ethical approval and was conducted in accordance with the international ethical guidelines. Discussion This randomized controlled trial aims to evaluate interactive voice response technology in the context of resource-limited settings with a high burden of TB and high illiteracy rates. The software to be evaluated was developed using HCD and the intervention was based on the IMB model. The software is tailored to the local context and is interoperable with the MHI ecosystem. The HCD approach ensures higher usability of the MHI by integrating human factors in the prototype development. This research will contribute towards the understanding of the implementation and impact of the MHI on TB treatment outcomes and the health system, especially in LMICs. Trial registration ClinicalTrials.govNCT04709159. Registered on January 14, 2021.

To appreciate coastal trophodynamics, it is necessary to understand the dynamics and control of the spring and late summer/autumn phytoplankton blooms. Classically mesozooplankton are considered as main players in these blooms. Microzooplankton likely also are important in these dynamics, but their role is poorly understood. Critically, due to their rapid generation times, microzooplankton may exhibit rapid shifts during blooms. Through field sampling and rate measurements (dilution experiments) in a well-studied temperate coastal ecosystem (Helgoland, southern North Sea) we ask if there are differences in the trends exhibited between and within the spring and late summer/autumn blooms. To achieve this, we examined early, mid and late bloom periods in both seasons. We found 1) a shift in trophic composition during both blooms, with a trend from strongly autotrophic mixotrophs (e.g. Mesodinium) to mixotrophs and then towards heterotrophs; 2) an increase in intraguild predation at the end of the blooms; and 3) although microzooplankton were major consumers of the spring bloom (grazing coefficient g: 0.23–0.25 d−1; daily percent loss of production Pp: 36–47%), they were unlikely to control it, while in contrast, microzooplankton appeared to play a major role in controlling the late summer/autumn bloom (grazing coefficient g: 0.14–1.53 d−1; daily percent loss of production Pp: 24–103%). In doing so, we suggest that any simplifications that consider these seasonal blooms to be relatively homogeneous and similar will lead to substantial errors in the assessment of coastal trophodynamics.