Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys.

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DANs), and Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson's disease (PD) patients. Here, we obtained well-characterized DANs from hESCs and transplanted them into two parkinsonian monkeys to assess their behavioral and imaging changes. DANs from hESCs expressed dopaminergic markers, generated action potentials, and released dopamine (DA) in vitro. These neurons were transplanted bilaterally into the putamen of parkinsonian NHPs, and using magnetic resonance imaging techniques, we calculated the fractional anisotropy (FA) and mean diffusivity (MD), both employed for the first time for these purposes, to detect in vivo axonal and cellular density changes in the brain. Likewise, positron-emission tomography scans were performed to evaluate grafted DANs. Histological analyses identified grafted DANs, which were quantified stereologically. After grafting, animals showed signs of partially improved motor behavior in some of the HALLWAY motor tasks. Improvement in motor evaluations was inversely correlated with increases in bilateral FA. MD did not correlate with behavior but presented a negative correlation with FA. We also found higher 11C-DTBZ binding in positron-emission tomography scans associated with grafts. Higher DA levels measured by microdialysis after stimulation with a high-potassium solution or amphetamine were present in grafted animals after ten months, which has not been previously reported. Postmortem analysis of NHP brains showed that transplanted DANs survived in the putamen long-term, without developing tumors, in immunosuppressed animals. Although these results need to be confirmed with larger groups of NHPs, our molecular, behavioral, biochemical, and imaging findings support the integration and survival of human DANs in this pre-clinical PD model.

Latent tuberculosis infection (LTBI) in health-care workers: a cross-sectional study at a northern Peruvian hospital.

Background: Healthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs' characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital. Methods: This study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative. Results: We recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84-22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01-2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44-3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09-13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27-4.08) compared to those HCWs not occupationally exposed. Conclusion: The LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.

Dopaminergic Dependency of Cholinergic Pallidal Neurons.

We employed the whole-cell patch-clamp method and ChAT-Cre mice to study the electrophysiological attributes of cholinergic neurons in the external globus pallidus. Most neurons were inactive, although approximately 20% displayed spontaneous firing, including burst firing. The resting membrane potential, the whole neuron input resistance, the membrane time constant and the total neuron membrane capacitance were also characterized. The current-voltage relationship showed time-independent inward rectification without a "sag". Firing induced by current injections had a brief initial fast adaptation followed by tonic firing with minimal accommodation. Intensity-frequency plots exhibited maximal average firing rates of about 10 Hz. These traits are similar to those of some cholinergic neurons in the basal forebrain. Also, we examined their dopamine sensitivity by acutely blocking dopamine receptors. This action demonstrated that the membrane potential, excitability, and firing pattern of pallidal cholinergic neurons rely on the constitutive activity of dopamine receptors, primarily D2-class receptors. The blockade of these receptors induced a resting membrane potential hyperpolarization, a decrease in firing for the same stimulus, the disappearance of fast adaptation, and the emergence of a depolarization block. This shift in physiological characteristics was evident even when the hyperpolarization was corrected with D.C. current. Neither the currents that generate the action potentials nor those from synaptic inputs were responsible. Instead, our findings suggest, that subthreshold slow ion currents, that require further investigation, are the target of this novel dopaminergic signaling.

Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study.

BACKGROUND: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America. METHODS: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics. FINDINGS: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29). INTERPRETATION: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer. FUNDING: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Impact of hospital characteristics on implementation of a Pediatric Early Warning System in resource-limited cancer hospitals.

Background: Pediatric Early Warning Systems (PEWS) aid in identification of deterioration in hospitalized children with cancer but are underutilized in resource-limited settings. Proyecto EVAT is a multicenter quality improvement (QI) collaborative in Latin America to implement PEWS. This study investigates the relationship between hospital characteristics and time required for PEWS implementation. Methods: This convergent mixed-methods study included 23 Proyecto EVAT childhood cancer centers; 5 hospitals representing quick and slow implementers were selected for qualitative analysis. Semi-structured interviews were conducted with 71 stakeholders involved in PEWS implementation. Interviews were recorded, transcribed and translated to English, then coded using a priori and novel codes. Thematic content analysis explored the impact of hospital characteristics and QI experience on time required for PEWS implementation and was supplemented by quantitative analysis exploring the relationship between hospital characteristics and implementation time. Results: In both quantitative and qualitative analysis, material and human resources to support PEWS significantly impacted time to implementation. Lack of resources produced various obstacles that extended time necessary for centers to achieve successful implementation. Hospital characteristics, such as funding structure and type, influenced PEWS implementation time by determining their resource-availability. Prior hospital or implementation leader experience with QI, however, helped facilitate implementation by assisting implementers predict and overcome resource-related challenges. Conclusions: Hospital characteristics impact time required to implement PEWS in resource-limited childhood cancer centers; however, prior QI experience helps anticipate and adapt to resource challenges and more quickly implement PEWS. QI training should be a component of strategies to scale-up use of evidence-based interventions like PEWS in resource-limited settings.

Model for regional collaboration: Successful strategy to implement a pediatric early warning system in 36 pediatric oncology centers in Latin America.

BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.

Spontaneous Activity of Neuronal Ensembles in Mouse Motor Cortex: Changes after GABAergic Blockade.

The mouse motor cortex exhibits spontaneous activity in the form of temporal sequences of neuronal ensembles in vitro without the need of tissue stimulation. These neuronal ensembles are defined as groups of neurons with a strong correlation between its firing patterns, generating what appears to be a predetermined neural conduction mode that needs study. Each ensemble is commonly accompanied by one or more parvalbumin expressing neurons (PV+) or fast spiking interneurons. Many of these interneurons have functional connections between them, helping to form a circuit configuration similar to a small-world network. However, rich club metrics show that most connected neurons are neurons not expressing parvalbumin, mainly pyramidal neurons (PV-) suggesting feed-forward propagation through pyramidal cells. Ensembles with PV+ neurons are connected to these hubs. When ligand-gated fast GABAergic transmission is blocked, temporal sequences of ensembles collapse into a unique synchronous and recurrent ensemble, showing the need of inhibition for coding cortical spontaneous activity. This new ensemble has a duration and electrophysiological characteristics of brief recurrent interictal epileptiform discharges (IEDs) composed by the coactivity of both PV- and PV+ neurons, demonstrating that GABA transmission impedes its occurrence. Synchronous ensembles are clearly divided into two clusters one of them lasting longer and mainly composed by PV+ neurons. Because an ictal-like event was not recorded after several minutes of IEDs recording, it is inferred that an external stimulus and/or fast GABA transmission are necessary for its appearance, making this preparation ideal to study both the neuronal machinery to encode cortical spontaneous activity and its transformation into brief non-ictal epileptiform discharges.

Gynecologic Care for Women With Physical Disabilities: A Qualitative Study of Patients and Providers.

BACKGROUND: Women with physical disabilities have unmet gynecologic care needs, including disparities in cancer screening and contraceptive care, when compared with women without physical disabilities. Our objective was to qualitatively assess provider and patient perspectives regarding barriers to gynecologic health care for women with physical disabilities. METHODS: We used purposive sampling to recruit women with physical disabilities and gynecology providers who had experience caring for this population at two university hospitals. Patient and provider participants completed in-depth, semistructured interviews investigating their experiences with and barriers to receiving or providing gynecologic care. Transcripts were systematically analyzed by reviewing assigned codes and performing thematic analysis. We planned a sample size of at least 20 patient and provider participants to allow for saturation of thematic content. RESULTS: We interviewed 29 women with physical disabilities and 20 providers. Important themes for providers and patients centered around adequate time spent during appointments, challenges with the gynecologic examination, inadequate facilities, clinical space limitations, and lack of formal provider and staff training in caring for this population. CONCLUSIONS: Providers were motivated to provide quality care for women with disabilities, but encountered systems and training barriers. Patients and providers had concordant impressions of barriers that influenced equitable and patient-centered care, with structural barriers, including a lack of accessible space, closely related to perceptions of health care inequity between women with and without physical disabilities.

Fertility considerations and attitudes about family planning among women with cystic fibrosis.

OBJECTIVE: Our objective was to explore knowledge, attitudes and beliefs about pregnancy and contraceptive decision-making among reproductive-aged women with cystic fibrosis. STUDY DESIGN: In this qualitative study, we used purposive sampling of reproductive age women enrolled in the Adult Cystic Fibrosis program at Penn Medicine. We conducted semistructured one-on-one interviews lasting 30-60 min. Interviews were audio-recorded and transcribed verbatim. Data were analyzed using thematic analysis. RESULTS: We interviewed 24 women. Participants described shortened life span, personal health status and impact of cystic fibrosis on a potential child as three factors that were central to family planning. Future pregnancy intentions, perception of fertility including misconceptions and provider counseling influenced related contraception utilization. CONCLUSIONS: Women with cystic fibrosis described thoughtful considerations about desired pregnancies to be planned during times of optimal health. Gaps in knowledge may limit a woman's ability to make the most informed family planning decisions. IMPLICATIONS: Having cystic fibrosis directly affects women's decisions around pregnancy and family planning. Understanding what motivates women with cystic fibrosis to use or not to use contraception can improve family planning care delivery to this population.

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism.

Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20-40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia. Here we use in vitro slice preparations including the SNr to observe drug-induced pathological firing by using drugs that most likely produce it, DA-receptor antagonists (SCH23390 plus sulpiride), to compare with firing patterns found in DA-depleted tissue. The hypothesis is that SNr firing would be similar under both conditions, a prerequisite to the proposal of a similar preparation to test other DIP-producing drugs. Firing was analyzed with three complementary metrics, showing similarities between DA depletion and acute DA-receptor blockade. Moreover, blockade of either nonselective cationic channels or Cav3 T-type calcium channels hyperpolarized the membrane and abolished bursting and irregular firing, silencing SNr neurons in both conditions. Therefore, currents generating firing in control conditions are in part responsible for pathological firing. Haloperidol, a DIP-producing drug, reproduced DA-receptor antagonist firing modifications. Since acute DA-receptor blockade induces SNr neuron firing similar to that found in the 6-hydroxydopamine model of PS, output basal ganglia neurons may play a role in generating DIP. Therefore, this study opens the way to test other DIP-producing drugs. NEW & NOTEWORTHY Dopamine (DA) depletion enhances substantia nigra pars reticulata (SNr) neuron bursting and irregular firing, hallmarks of Parkinsonism. Several drugs, including antipsychotics, antidepressants, and calcium channel antagonists, among others, produce drug-induced Parkinsonism. Here we show the first comparison between SNr neuron firing after DA depletion vs. firing found after acute blockade of DA receptors. It was found that firing in both conditions is similar, implying that pathological SNr neuron firing is also a physiological correlate of drug-induced Parkinsonism.

Calcium currents in striatal fast-spiking interneurons: dopaminergic modulation of CaV1 channels.

BACKGROUND: Striatal fast-spiking interneurons (FSI) are a subset of GABAergic cells that express calcium-binding protein parvalbumin (PV). They provide feed-forward inhibition to striatal projection neurons (SPNs), receive cortical, thalamic and dopaminergic inputs and are coupled together by electrical and chemical synapses, being important components of the striatal circuitry. It is known that dopamine (DA) depolarizes FSI via D1-class DA receptors, but no studies about the ionic mechanism of this action have been reported. Here we ask about the ion channels that are the effectors of DA actions. This work studies their Ca2+ currents. RESULTS: Whole-cell recordings in acutely dissociated and identified FSI from PV-Cre transgenic mice were used to show that FSI express an array of voltage gated Ca2+ channel classes: CaV1, CaV2.1, CaV2.2, CaV2.3 and CaV3. However, CaV1 Ca2+ channel carries most of the whole-cell Ca2+ current in FSI. Activation of D1-like class of DA receptors by the D1-receptor selective agonist SKF-81297 (SKF) enhances whole-cell Ca2+ currents through CaV1 channels modulation. A previous block of CaV1 channels with nicardipine occludes the action of the DA-agonist, suggesting that no other Ca2+ channel is modulated by D1-receptor activation. Bath application of SKF in brain slices increases the firing rate and activity of FSI as measured with both whole-cell and Ca2+ imaging recordings. These actions are reduced by nicardipine. CONCLUSIONS: The present work discloses one final effector of DA modulation in FSI. We conclude that the facilitatory action of DA in FSI is in part due to CaV1 Ca2+ channels positive modulation.

Treatment Decisions at the Time of Miscarriage Diagnosis.

OBJECTIVE: To describe the factors patients and physicians prioritize during first-trimester miscarriage management and assess what drives satisfaction with care. METHODS: We conducted a mixed-methods study of clinically stable women seeking surgical, medical, or expectant miscarriage treatment. Women with first-trimester fetal demise or anembryonic gestation (N=55) completed demographic and psychosocial surveys. Using purposive sampling, 45 (82%) completed in-depth interviews. Fifteen obstetricians were interviewed. Participants described factors that informed their counseling (physicians) or decision-making (patients). Content analysis used an integrated approach with inductively and deductively derived codes. Patient-derived themes were stratified by treatment choice. Associations between variables and treatment choices were analyzed. RESULTS: Thirty-four women (62%) received surgical management, 19 (35%) received medical, and two (4%) received expectant. Physicians expected that women with prior pregnancies have strong management preferences, and indeed, multigravid patients were less likely to change their initial treatment choice after counseling than primigravid patients (12% compared with 42%, odds ratio [OR] 0.18, 95% confidence interval [CI] 0.04-0.81, P=.03). Physicians favored patient-centered decisions and patients chose the treatment that they thought would least affect other responsibilities. Those ultimately receiving surgical management had a higher monthly income (adjusted OR 1.30, 95% CI 1.04-1.63, P=.023) and more social support (adjusted OR 2.45, 95% CI 1.07-5.61, P=.035) than the medical group. The surgical group cited loss acceptance, a favorable perception of surgery, and a desire to expedite the miscarriage as decisive factors. The medical group endorsed control over, and timed completion of, the miscarriage in a more intimate setting, an aversion to surgery or anesthesia, and a perception of improved fertility preservation as decisive factors. Regardless of treatment choice, satisfaction with treatment was linked to a supportive clinical team and expeditious resolution. CONCLUSION: Prior pregnancy experiences, obligations, and sociodemographic factors influence miscarriage management decision-making. Structured counseling, especially for primigravid patients, could improve both the physician and the patient experience with miscarriage care.

Clinical Trial Decision Making in Pediatric Sickle Cell Disease: A Qualitative Study of Perceived Benefits and Barriers to Participation.

Clinical trial research forms the foundation for advancing treatments; yet, children with sickle cell disease (SCD) are currently underrepresented. This qualitative study examines decision-making processes of youth with SCD and their caregivers regarding enrollment in clinical trial research. A subsample of participants from a study of clinical trial decision making among youth with health disparity conditions, 23 caregivers and 29 children/teens/young adults with SCD (age, 10 to 29 y), indicated whether or not they would participate in hypothetical medical and psychosocial clinical trials and prioritized barriers and benefits to participation via card sort and semistructured interviews. Audio recordings were transcribed and coded for themes. Participants reported that concerns of potential harm most affected their decision. Secondary factors were potential benefit, manageable study demands, and trust in the medical staff. Caregivers weighed potential harm more heavily than their children. Young children were more likely to endorse potential benefit. Overall, participants stated they would be willing to participate in research if the potential benefit outweighs potential harm and unmanageable study demands. To optimize recruitment, results suggest addressing potential harm first while highlighting potential benefits, creating manageable study demands, and endorsing the future benefits of research to the sickle cell community.

Initial development of a questionnaire evaluating perceived benefits and barriers to pediatric clinical trials participation.

OBJECTIVE: To evaluate perceived benefits and barriers to pediatric clinical trials participation to improve decision-making and enhance recruitment and retention among minority youth with chronic health conditions (sickle cell disease, asthma) and their caregivers. METHODS: A questionnaire was developed based on the social ecological model using input from medical experts and community-based public health organizations. Parallel caregiver, adolescent/young adult (AYA; 16-39 years old), and child (8-15 years old) versions were field tested. Patients and caregivers completed the questionnaire, which included demographic items, perceived life stress and social desirability measures. RESULTS: Exploratory factor analysis rendered a four-factor solution for the caregiver version (direct treatment benefit, mistrust of research/researchers, trust in healthcare team to engage in safe research, and opportunity cost) and the AYA version (mistrust/no direct benefit, safety, direct treatment benefit/practical considerations, and social support for research). Factor structures differed for SCD and asthma caregivers; results were equivocal for the child version. Summated subscales were not significantly associated with patient demographics or social desirability, but significant correlations with perceived life stress and prior participation in research were identified. CONCLUSIONS: While the factor structure should be confirmed with larger samples, findings indicate potential benefit, perceived harm due to mistrust of researchers, and logistics are primary factors in decision-making about participation in pediatric clinical trials. By addressing these benefits/barriers through adjustments to recruitment and informed consent procedures, researchers may address misperceptions of research, improve decision-making, and increase recruitment and retention particularly for ethnic minority children with chronic health conditions.

Classification of climate-change-induced stresses on biological diversity.

Conservation actions need to account for and be adapted to address changes that will occur under global climate change. The identification of stresses on biological diversity (as defined in the Convention on Biological Diversity) is key in the process of adaptive conservation management. We considered any impact of climate change on biological diversity a stress because such an effect represents a change (negative or positive) in key ecological attributes of an ecosystem or parts of it. We applied a systemic approach and a hierarchical framework in a comprehensive classification of stresses to biological diversity that are caused directly by global climate change. Through analyses of 20 conservation sites in 7 countries and a review of the literature, we identified climate-change-induced stresses. We grouped the identified stresses according to 3 levels of biological diversity: stresses that affect individuals and populations, stresses that affect biological communities, and stresses that affect ecosystem structure and function. For each stress category, we differentiated 3 hierarchical levels of stress: stress class (thematic grouping with the coarsest resolution, 8); general stresses (thematic groups of specific stresses, 21); and specific stresses (most detailed definition of stresses, 90). We also compiled an overview of effects of climate change on ecosystem services using the categories of the Millennium Ecosystem Assessment and 2 additional categories. Our classification may be used to identify key climate-change-related stresses to biological diversity and may assist in the development of appropriate conservation strategies. The classification is in list format, but it accounts for relations among climate-change-induced stresses.

Human metapneumovirus and other respiratory viral infections in children attending a day care center.

Human metapneumovirus (hMPV) is an important cause of acute respiratory infections (ARI). We studied 335 ARI episodes in 74 children<5 years of age attending a day care center during a 1-year period to detect the presence of hMPV and other viruses. Seven (9.5%) children were infected by hMPV and this virus accounted for 2.1% of the ARI episodes.

The effect of repetition on imitation from television during infancy.

Although television exposure levels during infancy are high, the impact of such exposure on learning is relatively unknown. Initial studies have shown that infants imitate significantly fewer target actions from a televised demonstration than they imitate from a live demonstration. It was hypothesized that increasing the duration of exposure to the videotaped demonstration would increase learning from television. Independent groups of 12- to 21-month-olds were exposed to live or videotaped demonstrations of target actions, and imitation of the target actions was measured 24 hr later. The video segment duration was twice that of the live presentation. Doubling exposure increased levels of imitation performance in the video groups to that of the live groups, and both groups exceeded baseline performance. These results are consistent with the perceptual encoding impoverishment theory, and we conclude that repeated exposure enhances encoding of the target actions from a 2D television source.

Encefalocele Frontoetmoideo-nasoorbitario criterios para manejo quirúrgico A propósito de un caso / Frontoethmoid-nasoorbital encephalocele criteria for surgical management About a case

Los meningoencefaloceles son molformaciones congénitas, con una alta incidencia en la selva amazónica ecuatoriana. La variedad fronto-etmoidal es la más común y requiere tratamiento quirúrgico temprano. Los autores combinan un abordaje neuroquirúrgico y craneofacial realizado en un solo tiempo para corregir este tipo de defecto.

Meningoencephaloceles are congenital molformations, with a high incidence in the Ecuadorian Amazon jungle. The fronto-ethmoidal variety is the most common and requires early surgical treatment. The authors combine a neurosurgical and craniofacial approach performed in a single time to correct this type of defect.