Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings

Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

Whole body bone scintigraphy in osseous hydatosis: a case report

Hydatid disease is common in many parts of the world, and causes considerable health and economic loss. This disease may develop in almost any part of the body

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer

The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a potentially curative oesophagectomy for squamous or adenocarcinoma were reviewed retrospectively. As part of the procedure, all patients underwent an en-bloc resection of their periesophageal tissue. The presence of tumour either at, or within, 1 mm of the CRM was recorded and correlated with their TNM and survival data. A total of 67 patients (20%) were noted to have a positive CRM, of which 40 cases (12%) had tumour at the resection margin and the remainder had tumour within 1 mm of the margin. Univariate analysis showed no statistically significant association between survival and either category of CRM involvement. Multivariate analysis showed that only T-stage, nodal status and tumour grade were prognostic markers. In conclusion, the presence of microscopic tumour at the CRM following an en-bloc oesophagectomy is not a significant prognostic marker

Aversive Learning in Honeybees Revealed by the Olfactory Conditioning of the Sting Extension Reflex

Invertebrates have contributed greatly to our understanding of associative learning because they allow learning protocols to be combined with experimental access to the nervous system. The honeybee Apis mellifera constitutes a standard model for the study of appetitive learning and memory since it was shown, almost a century ago, that bees learn to associate different sensory cues with a reward of sugar solution. However, up to now, no study has explored aversive learning in bees in such a way that simultaneous access to its neural bases is granted. Using odorants paired with electric shocks, we conditioned the sting extension reflex, which is exhibited by harnessed bees when subjected to a noxious stimulation. We show that this response can be conditioned so that bees learn to extend their sting in response to the odorant previously punished. Bees also learn to extend the proboscis to one odorant paired with sugar solution and the sting to a different odorant paired with electric shock, thus showing that they can master both appetitive and aversive associations simultaneously. Responding to the appropriate odorant with the appropriate response is possible because two different biogenic amines, octopamine and dopamine subserve appetitive and aversive reinforcement, respectively. While octopamine has been previously shown to substitute for appetitive reinforcement, we demonstrate that blocking of dopaminergic, but not octopaminergic, receptors suppresses aversive learning. Therefore, aversive learning in honeybees can now be accessed both at the behavioral and neural levels, thus opening new research avenues for understanding basic mechanisms of learning and memory

Reconsidering the use of rankings in the valuation of health states: a model for estimating cardinal values from ordinal data

BACKGROUND: In survey studies on health-state valuations, ordinal ranking exercises often are used as precursors to other elicitation methods such as the time trade-off (TTO) or standard gamble, but the ranking data have not been used in deriving cardinal valuations. This study reconsiders the role of ordinal ranks in valuing health and introduces a new approach to estimate interval-scaled valuations based on aggregate ranking data. METHODS: Analyses were undertaken on data from a previously published general population survey study in the United Kingdom that included rankings and TTO values for hypothetical states described using the EQ-5D classification system. The EQ-5D includes five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) with three possible levels on each. Rank data were analysed using a random utility model, operationalized through conditional logit regression. In the statistical model, probabilities of observed rankings were related to the latent utilities of different health states, modeled as a linear function of EQ-5D domain scores, as in previously reported EQ-5D valuation functions. Predicted valuations based on the conditional logit model were compared to observed TTO values for the 42 states in the study and to predictions based on a model estimated directly from the TTO values. Models were evaluated using the intraclass correlation coefficient (ICC) between predictions and mean observations, and the root mean squared error of predictions at the individual level. RESULTS: Agreement between predicted valuations from the rank model and observed TTO values was very high, with an ICC of 0.97, only marginally lower than for predictions based on the model estimated directly from TTO values (ICC = 0.99). Individual-level errors were also comparable in the two models, with root mean squared errors of 0.503 and 0.496 for the rank-based and TTO-based predictions, respectively. CONCLUSIONS: Modeling health-state valuations based on ordinal ranks can provide results that are similar to those obtained from more widely analyzed valuation techniques such as the TTO. The information content in aggregate ranking data is not currently exploited to full advantage. The possibility of estimating cardinal valuations from ordinal ranks could also simplify future data collection dramatically and facilitate wider empirical study of health-state valuations in diverse settings and population groups

The pyramidalis-anterior pubic ligament-adductor longus complex (PLAC) and its role with adductor injuries: a new anatomical concept.

PURPOSE: Adductor longus injuries are complex. The conflict between views in the recent literature and various nineteenth-century anatomy books regarding symphyseal and perisymphyseal anatomy can lead to difficulties in MRI interpretation and treatment decisions. The aim of the study is to systematically investigate the pyramidalis muscle and its anatomical connections with adductor longus and rectus abdominis, to elucidate injury patterns occurring with adductor avulsions. METHODS: A layered dissection of the soft tissues of the anterior symphyseal area was performed on seven fresh-frozen male cadavers. The dimensions of the pyramidalis muscle were measured and anatomical connections with adductor longus, rectus abdominis and aponeuroses examined. RESULTS: The pyramidalis is the only abdominal muscle anterior to the pubic bone and was found bilaterally in all specimens. It arises from the pubic crest and anterior pubic ligament and attaches to the linea alba on the medial border. The proximal adductor longus attaches to the pubic crest and anterior pubic ligament. The anterior pubic ligament is also a fascial anchor point connecting the lower anterior abdominal aponeurosis and fascia lata. The rectus abdominis, however, is not attached to the adductor longus; its lateral tendon attaches to the cranial border of the pubis; and its slender internal tendon attaches inferiorly to the symphysis with fascia lata and gracilis. CONCLUSION: The study demonstrates a strong direct connection between the pyramidalis muscle and adductor longus tendon via the anterior pubic ligament, and it introduces the new anatomical concept of the pyramidalis-anterior pubic ligament-adductor longus complex (PLAC). Knowledge of these anatomical relationships should be employed to aid in image interpretation and treatment planning with proximal adductor avulsions. In particular, MRI imaging should be employed for all proximal adductor longus avulsions to assess the integrity of the PLAC

Frustrated hierarchical synchronization and emergent complexity in the human connectome network

The spontaneous emergence of coherent behavior through synchronization plays a key role in neural function, and its anomalies often lie at the basis of pathologies. Here we employ a parsimonious (mesoscopic) approach to study analytically and computationally the synchronization (Kuramoto) dynamics on the actual human-brain connectome network. We elucidate the existence of a so-far-uncovered intermediate phase, placed between the standard synchronous and asynchronous phases, i.e. between order and disorder. This novel phase stems from the hierarchical modular organization of the connectome. Where one would expect a hierarchical synchronization process, we show that the interplay between structural bottlenecks and quenched intrinsic frequency heterogeneities at many different scales, gives rise to frustrated synchronization, metastability, and chimera-like states, resulting in a very rich and complex phenomenology. We uncover the origin of the dynamic freezing behind these features by using spectral graph theory and discuss how the emerging complex synchronization patterns relate to the need for the brain to access –in a robust though flexible way– a large variety of functional attractors and dynamical repertoires without ad hoc fine-tuning to a critical pointWe acknowledge financial support from J. de Andalucía, grant P09-FQM-4682 and we thank O. Sporns for providing us access to the human connectome data

Neuropathic Pain in Rats with a Partial Sciatic Nerve Ligation Is Alleviated by Intravenous Injection of Monoclonal Antibody to High Mobility Group Box-1

High mobility group box-1 (HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that intravenous injection of anti-HMGB1 monoclonal antibody significantly attenuated brain edema in a rat model of stroke, possibly by attenuating glial activation. Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating peripheral nerve injury-induced pain. Following partial sciatic nerve ligation (PSNL), rats were treated with either anti-HMGB1 or control IgG. Intravenous treatment with anti-HMGB1 monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile hypersensitivity at 7, 14 and 21 days, but not 3 days, after ligation, whereas control IgG had no effect on tactile hypersensitivity. The expression of HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of HMGB1 protein. Also, the injury-induced translocation of HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of HMGB1. Markers of astrocyte (glial fibrillary acidic protein (GFAP)), microglia (ionized calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the sham-operated side 21 days after PSNL. Anti-HMGB1 monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of neuropathic pain. Thus, the targeting of HMGB1 could be a useful therapeutic strategy in the treatment of chronic pain