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There is a strong rationale for investigating nutritional interventions with docosahexaenoic acid (DHA) in cancer prevention and therapy; however, the effects of DHA on ovarian cancer (OC) have not...

Univentricular heart disease accounts for ~1.25% of all congenital heart disease. Such cases remain among the most challenging to manage, typically requiring a three-staged palliation. The first stage involves placement of a systemic to pulmonary shunt. While a variety of shunt types, including ductal stenting, can be used to manage univentricular conditions, the archetype remains the Blalock-Taussig (BT) shunt. While waiting future palliative intervention at home, intercurrent illness may necessitate presentation to a district general hospital where subspecialist advice and assessment is remote. This review aims to present the general paediatrician with a straightforward BT shunt physiology overview highlighting unique complications which may complicate intercurrent illness.

Pulse oximetry is a first-line monitoring tool, used in neonatal medicine routinely as a part of continuous monitoring during intensive care. It is also used to guide response to resuscitation and as a screening tool for congenital heart disease. Despite its widespread use, many healthcare providers are unaware of the underlying principles and limitations of pulse oximetry in neonates. In this article, we will discuss the physiological and technological principles behind the use of saturation monitoring and its use in neonatal practice.

Aims Exchange transfusion is becoming less frequently performed in neonatology. It is however still advocated in a myriad of paediatric disorders. Evidence describing the frequency of exchange transfusion within the paediatric population is limited. This retrospective observational study aims to describe the epidemiology of exchange transfusion within UK and Irish Paediatric Intensive Care Units. Methods Retrospective data was requested from the Paediatric Intensive Care Audit network (PICAnet) with regards to completed exchange transfusions within Paediatric Intensive Care Units (PICU) from the UK & Ireland between 2007 and 2015. Results In total 559 exchange transfusions within UK and Irish PICUs were reported to PICAnet between January 2007 and December 2015. During this time 167,462 PICU admissions were also reported. This equated to an average of 62.1 exchange transfusions per year and an incidence of 3.3 exchange transfusions per 1000 PICU admissions. During the study period, exchange transfusion rate varied by age, with: 16.1% occurring in neonates, 24.9% in non-neonates 12 year olds. The observed frequency of commonly recognised indications for all reported exchange transfusions were; Sickle cell disease 37.2%, pertussis 4.7%, neonatal jaundice 3%, leukaemia 3%, neonatal polycythaemia 0.4% and neonatal anaemia 0.2%. No exchange transfusions were performed for malaria. The indication for exchange transfusion was unclear in 41% whilst 10.6% of exchange transfusions occurred in a reported setting of solitary congenital heart disease. 90% of children requiring exchange transfusion within PICU survived to PICU discharge. Conclusions Exchange transfusion was reported in 3.3 per 1000 UK and Irish PICU admissions between 2007 and 2015. The majority (41%) occurred in children under 2 years of age. The most common indication for exchange transfusion within PICU was sickle cell disease. Acknowledgement The authors would like to thank PICAnet for providing the data using in the study.

A healthy 15-month-old girl presented to the emergency department with a 24-hour history of fever and rash. The initial blanching rash developed into non-blanching areas with associated leg swelling. She had received no recent medications, had no known drug allergies and no unwell contacts.On examination, she was feverish at 38.6°C, capillary refill time was2 s with warm peripheries, heart rate 169 bpm and blood pressure 94/59 mm Hg. A palpable purpuric rash was evident on all four limbs and face (figure 1) although the trunk was spared. Her legs were tense and oedematous to the knee.edpract;103/1/25/EDPRACT2016311782F1F1EDPRACT2016311782F1Figure 1Rash at presentation.Initial investigations: Haemoglobin level: 131 g/L, white cell count: 16.6×10What is the diagnosis? Henoch-Schonlein purpura (HSP)Meningococcal septicaemiaAcute haemorrhagic oedema of infancy (AHOI)Vasculitic urticariaGianotti-Crosti syndromeWhat further investigation is required? Check viral serology including Epstein-Barr virus and hepatitis B virusComplement levels and autoimmune screenSkin biopsyLumbar puncture and audiologyNo further investigationHow should this child be managed? Complete 7 days of ceftriaxone treatmentOral aciclovirOral steroidsRegular follow-up with urinalysis and blood pressure monitoringStop antibiotics if cultures were negative at 48 hours and discharge

A 13-year-old boy with a background of Prader-Willi syndrome (PWS) was admitted to the regional paediatric intensive care unit, with community-acquired pneumonia. Despite a week of intravenous antibiotics, resolution of inflammatory markers and resolving consolidation on radiograph, he remained feverish. Fever of unknown origin investigations were negative and he was diagnosed with central thermal dysregulation secondary to hypothalamic dysfunction in PWS. Following a hyperpyrexia period, secondary rhabdomyolysis and renal failure developed. This was successfully managed with active cooling, ventilation and haemofiltration. After weaning from haemofiltration, the patient was successfully extubated to non-invasive respiratory support.

Needle cricothyroidotomy is a simple but potentially life-saving emergency airway manoeuvre used to provide oxygenation during a ‘cannot intubate, cannot ventilate’ (CICV) emergency.1 ,2 The procedure involves inserting a large bore cannula through the cricothyroid membrane and can be performed in patients of all ages.3 It is, however, only a short-term oxygenation solution prior to insertion of a definitive airway.1 The procedure is taught on Advanced Paediatric Life Support (APLS) courses where focus is on needle cricothyroidotomy insertion and not subsequent airway utilisation.3 This along with the rarity of this emergency means practical experience is lacking. Problems, such as equipment availability and poor assembly, would likely arise when the manoeuvre is required, which could be disastrous during this time-critical emergency. In this study, we show that introduction of a simulation-based training bundle improves: 1. Successful simulated patient oxygenation 2. Time taken to oxygenation 3. APLS provider confidence Invited APLS providers within a tertiary paediatric hospital were given the same hypothetical CICV scenario where a simulated patient has a needle cricothyroidotomy airway in situ. The project was registered with the local trust governance department. Candidates were asked, within a maximum time of 10 min, to collect and assemble suitable equipment to oxygenate or ventilate the patient. Candidates were then shown a standardised video tutorial on needle cricothyroidotomy and introduced to a procedure pack containing all necessary equipment used within the …

A 2-year-old girl, with eczema and recurrent wheeze, was transferred from a district general hospital to the regional paediatric intensive care unit (PICU), following intubation. For 2 hours prior to intubation, she received continuous salbutamol and ipratropium nebulisers, hydrocortisone (4 mg/kg), magnesium sulfate, aminophylline (loading dose and infusion) and a loading dose of intravenous salbutamol. Despite this, she tired and developed type 2 respiratory failure, necessitating intubation with a 4.0 endotracheal tube (ETT), which was secured nasally at 17 cm. On arrival at the PICU, her wheeze had completely resolved. Chest radiograph showed left lower lobe consolidation, and bronchoalveolar lavage revealed purulent secretions. She was treated with intravenous antibiotics. Aminophylline infusion was stopped and nebuliser therapy spaced overnight to four hourly. The following morning, she suffered a sudden deterioration. Oxygen requirement rose from 21% to 60% and inspiratory pressure maintaining a tidal volume of 7 mL/kg (normal target 6–8 mL/kg) increased from 18 to 28 cm H2O. …

We examined the ways in which memories of previously seen obstacles can alter the stepping of walking cats. Cats were paused after the forelegs, but not the hindlegs, had stepped over an obstacle. Near the beginning of a variable delay period, the obstacle was lowered. On the subsequent step, the path of the hindlegs allowed us to make inferences about whether the memory of the obstacle was influencing leg movements. We present two main findings. First, the memory of the obstacle persisted for the duration that the animal straddled the original location of the obstacle. In one instance, this interval was 10 min. Second, this memory includes information regarding the size and position of the obstacle relative to the animal. This information is used to plan foot placement and to redirect the step in mid-swing to avoid the previous position of the obstacle.

In this investigation, we obtained data that support the hypothesis that afferent signals associated with hip flexion play a role in initiating the swing-to-stance transition of the hind legs in walking cats. Direct evidence came from observations in walking decerebrate cats. Assisting the flexion of the hip joint during swing advanced the onset of activity in ankle extensor muscles, and this advance was strongly correlated with a reduction in the duration of hip flexor muscle activity. The hip angle at the time of onset of the flexion to extension transition was similar during assisted and unassisted steps. Additional evidence for the hypothesis that sensory signals related to hip flexion are important in regulating the swing-to-stance transition came from four normal animals trained to walk in a variety of situations designed to alter the coordination of movements at the hip, knee, and ankle joints during the swing phase. Although there were exceptions in some tasks and preparations, the angle of the hip joint at the time of onset of extensor activity was generally less variable than that of the knee and ankle joints. We also found no clear relationships between the angle of the limb and body axes, or the length of the limb axis, and the time of onset of extensor activity. Finally, there were no indications that the stretching of ankle extensor muscles during swing was a factor in regulating the transition from swing-to-stance.

A 6-day-old term neonate who was intubated on day 1 of life for apnoeic episodes, was transferred to the regional paediatric intensive care unit (PICU) for specialist opinion following 3 failed extubations in the neonatal unit. Escherichia coli congenital pneumonia was diagnosed and the child discharged to the local hospital. Chest radiographs and inflammatory markers were in keeping with infection. However, ongoing difficulties with secretions necessitated readmission to the PICU, following a significant cyanotic episode associated with coughing. On arrival at the PICU, a large leak around the endotracheal tube (ETT) was noted. On direct laryngoscopy, the ETT was found correctly positioned, through the cords, but air was noted to be coming back from the oesophagus. Advancing the ETT towards the carina terminated the leak and raised the suspicion of a tracheo-oesophageal fistula. An H-type tracheo-oesophageal fistula was confirmed on bronchoscopy. An uneventful fistula repair was performed and the baby discharged from the PICU on day 23 of life.

Walking animals rely on working memory to avoid obstacles. One example is the stepping of the hindlegs of quadrupeds over an obstacle. In this case, the obstacle is not visible at the time of hindleg stepping, because of its position between the fore and hindlegs, and working memory must be used to avoid it. We have previously shown that this memory is very precise and surprisingly long-lasting and that it depends on the stepping of the forelegs over the obstacle for its initiation. In this study, we test the hypothesis that area 5 in the posterior parietal cortex of cats is necessary for the maintenance of this long-lasting working memory. We report that small bilateral lesions to area 5 do not affect the amplitude of normal stepping of the hindlegs over obstacles, but they profoundly reduce the long-lasting working memory of obstacles. We propose that inputs to area 5 associated with foreleg stepping initiate long-lasting activity that maintains the memory of obstacle height in another brain region to guide the hindlegs over obstacles.

To gain insight into the relative importance of force feedback to ongoing ankle extensor activity during walking in the conscious cat, we isolated the medial gastrocnemius muscle (MG) by denervating the other ankle extensors and measured the magnitude of its activity at different muscle lengths, velocities, and forces accomplished by having the animals walk up and down a sloped pegway. Mathematical models of proprioceptor dynamics predicted afferent activity and revealed that the changes in muscle activity under our experimental conditions were strongly correlated with Ib activity and not consistently associated with changes in Ia or group II activity. This allowed us to determine the gains within the force feedback pathway using a simple model of the neuromuscular system and the measured relationship between MG activity and force. Loop gain increased with muscle length due to the intrinsic force–length property of muscle. The gain of the pathway that converts muscle force to motoneuron depolarization was independent of length. To better test for a causal relationship between modulation of force feedback and changes in muscle activity, a second set of experiments was performed in which the MG muscle was perturbed during ground contact of the hind foot by dropping or lifting the peg underfoot. Collectively, these investigations support a causal role for force feedback and indicate that about 30% of the total muscle activity is due to force feedback during level walking. Force feedback's role increases during upslope walking and decreases during downslope walking, providing a simple mechanism for compensating for changes in terrain.

Introduction In many resource-limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long-term impact of initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted protease inhibitor (bPI)-based cART in British Columbia (BC), Canada. Methods We followed prospectively 3925 ART-naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL 500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL-matched bPI initiators (0.37 (0.29–0.45) vs. 0.46 (0.38–0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL. Conclusions Our results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI-based cART is to remain a preferred choice for first-line therapy in resource-limited settings.

A consistent feature of animal locomotion is the capacity to maintain stable movements in changing environments. Here we describe long-term modification of the swing movement of the hind leg in cats in response to repeatedly impeding the movement of the leg. While studying phase transitions in the hind legs, we discovered that repetitively evoking the stumbling-corrective reaction led to long-lasting increases in knee flexion and step height during swing to avoid the impediment. These increases were apparent after nearly 20 stimuli and maximal after about 120 stimuli and, in some animals, they persisted for ≥24 h after presentation of the stimuli. Furthermore, these long-lasting changes were context dependent and did not generalize to other environments; when walking was observed in an environment distinct from that used in training, the hind-limb kinematics returned to normal. To gain insight into what regions of the nervous system might be involved in this long-term modification, we examined the changes in stepping in decerebrate cats after multiple perturbed steps. In this situation, there was a short-term increase in step height, although this increase was smaller than that evoked in intact animals and persisted for

Background: Poor women have low rates of breast conservation therapy not explained by differences in insurance status or treatment preferences. The purpose of this study was to explore how low-income women make decisions about breast cancer treatment. Methods: Twenty-five women diagnosed with early-stage breast cancer through the Nebraska Every Woman Matters program were interviewed about their experiences selecting treatment options. These interviews were transcribed and then analysed using established qualitative techniques. Results: More than half of the women (n=16) described playing a passive role in decision making. Choice was determined by medical factors or not offered by their physicians. Intense emotional distress affected some women's ability to compare options. The women who did engage in a rational decision-making process (n=9) based their choices on concerns about body image and fear of recurrence. Conclusions: When presented with a choice, and when able to objectively weigh treatment options, low-income women base their treatment decisions on the same issues as those of higher income. Whether differences in income strata alter the doctor–patient power dynamic in favor of physician control over decision making, or whether low-income women are less prepared to engage in a rational deliberative process warrants further study. Copyright © 2001 John Wiley & Sons, Ltd.

The objective of this article is to review the literature regarding the risk of sudden infant death syndrome (SIDS) in bottle-fed infants compared to those that are breastfed. A meta-analysis and qualitative literature review were performed. Cohort and case-control studies were included if they met a minimum SIDS definition and presented data allowing calculation of an odds ratio (OR). Twenty-three studies were included in the meta-analysis. The studies were heterogeneous, and a majority (14) were of “fair” or “poor” quality. Crude ORs from 19 individual studies favored breastfeeding as protective against SIDS. The combined analysis indicated that bottle-fed infants were twice as likely to die from SIDS (pooled OR = 2.11; 95% CI 1.66-2.68). The results of the analysis showthat there is an association between bottle-feeding and SIDS, but this may be related to confounding variables.

The practice of injecting vitamins and antibiotics by lay people is common among Hispanic migrant farmworkers in the U.S.A. This practice has recent roots in the Latin American cultures from which these farmworkers originate, but it presents a public health concern in its new context because of the high prevalence of HIV infection among this disenfranchised population. Reasons for use of lay injections include cultural beliefs about the superiority of injections over oral forms of medications, perceived irrelevance of a professional diagnostician in prescribing empirical treatment, and a multitude of barriers to access to Western medicine. Although HIV educational materials directed at migrant farmworkers do not address the issue of sharing needles for these types of injections, some farmworkers indicated they had already modified their injection techniques in response to simple directives from physicians in their home country. In contrast to other folk treatment practices that have been resistant to change mediated solely through the provision of information, lay injection is such a new development that considerable experimentation and incorporation of new knowledge are still actively shaping its use. In this process, physicians are seen as legitimate sources of information about the use of Western pharmaceuticals; they should use this role to discourage unsafe injection practices. Efforts to extinguish the practice of lay injection entirely are less likely to meet with success so long as other means of accessing Western medicine are limited.

Vision is used by walking animals to ensure stable foot placements and to avoid obstacles in their path. Visual input is not used directly when walking over normal terrain, however. Instead, walking animals look three or four steps ahead of their current position and use short-term memory to remember pertinent objects for use at the appropriate time. In cluttered terrain, humans may rely on increased visual input, guiding foot movement directly when needed. In quadrupeds, the hindlegs can never beguided by visual input directly, suggesting a specialized memory system mightbe used during walking in cluttered terrain. We have previously reported evidence in support of this hypothesis, showing that cats that have stepped over an object with their forelegs and stopped remember its position for much longer (for up to ten minutes) than if they are stopped prior to stepping over it. In this presentation, I present research that tests the hypothesis that neural signals related to the movement of the forelegs are essential for the generation of this unique visual memory. By placing small lesions in cortical area 5, we disrupted the normal integration of sensory and motor signals in the parietal cortex. Cats with these lesions lost the long-lasting memory of straddled objects, and remembered these objects for no longer than if they had not stepped over them. The results support our hypothesis that a uniquely long-lasting memory system, initiated by neural signals related to foreleg stepping, is responsible for guiding the hindlegs of walking cats over obstacles. Funding from Canadian Institutes of Health Research and Alberta Heritage Foundation for Medical Research gratefully acknowledged.