The Emergence of Hierarchical Somatosensory Processing in Late Prematurity.

The somatosensory system has a hierarchical organization. Information processing increases in complexity from the contralateral primary sensory cortex to bilateral association cortices and this is represented by a sequence of somatosensory-evoked potentials recorded with scalp electroencephalographies. The mammalian somatosensory system matures over the early postnatal period in a rostro-caudal progression, but little is known about the development of hierarchical information processing in the human infant brain. To investigate the normal human development of the somatosensory hierarchy, we recorded potentials evoked by mechanical stimulation of hands and feet in 34 infants between 34 and 42 weeks corrected gestational age, with median postnatal age of 3 days. We show that the shortest latency potential was evoked for both hands and feet at all ages with a contralateral somatotopic source in the primary somatosensory cortex (SI). However, the longer latency responses, localized in SI and beyond, matured with age. They gradually emerged for the foot and, although always present for the hand, showed a shift from purely contralateral to bilateral hemispheric activation. These results demonstrate the rostro-caudal development of human somatosensory hierarchy and suggest that the development of its higher tiers is complete only just before the time of normal birth.

Investigation of Confounding Factors in Measuring Tissue Saturation with NIRS Spatially Resolved Spectroscopy.

Performing absolute measurements of tissue saturation of the brain with near-infrared spectroscopy (NIRS) is a clinically desirable brain monitoring tool. Tissue oxygenation index (TOI) is an indicator of absolute tissue mixed arterial and venous oxygen saturation, and can be calculated using a NIRS technique called spatially resolved spectroscopy (SRS). SRS instruments measure the change of light attenuation with distance by using multiple light source-detector distances at two or more wavelengths. The aim of the study is to use broadband NIRS SRS data to investigate the effects on the calculation of TOI of different parameters: wavelength selection, scattering dependence, source-detector distance, and resolving for water. In total, 55 neonates with hypoxic-ischemic encephalopathy were monitored using a broadband multi-distance continuous wave NIRS system; 172 datasets were recorded. Using a "Standard" approach, TOI values between 0 and 100% ("good") were calculated in 157/172 datasets with a mean TOI of 50%. By changing the wavelength selection, the number of "good" data sets increases to 165/172 with a mean of 60%. Alteration of the dependence of scattering on wavelength acts as a constant which shifts the absolute value of TOI significantly (p < 0.05), demonstrating the importance of having a subject-appropriate estimation of scattering dependence. In general, changing the combination of source-detector distances does not significantly alter the TOI (the mean TOI ranges from 41% to 53%) which suggests that the algorithm is robust to different source-detector combinations. The study shows the broadband NIRS SRS algorithm gives the opportunity to explore the calculation of TOI and could further improve the measurement of tissue saturation in a clinical setting.

Pet ownership increases human risk of encountering ticks.

We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products.

Risk factors for tick exposure in suburban settings in the Northeastern United States.

Prevention of tick-borne diseases requires an understanding of when and where exposure to ticks is most likely. We used an epidemiologic approach to define these parameters for residents of a Lyme-endemic region. Two persons in each of 500 Connecticut households were asked to complete a log each night for one week during June, 2013. Participants recorded their whereabouts in 15min increments (indoors, outdoors in their yard, outdoors on others' private property, or outdoors in public spaces) and noted each day whether they found a tick on themselves. Demographic and household information was also collected. Logs were completed for 934 participants in 471 households yielding 51,895 time-place observations. Median participant age was 49 years (range 2-91 years); 52% were female. Ninety-one participants (9.8%) reported finding a tick during the week, with slightly higher rates among females and minors. Household factors positively associated with finding a tick included having indoor/outdoor pets (odds ratio (OR)=1.7; 95% confidence interval (CI): 1.1-2.9), the presence of a bird feeder in the yard (OR=1.9; CI:1.2-3.2), and presence of an outdoor dining area (OR=2.2; CI:1.1-4.3). Individual factors associated with finding a tick on a given day were bathing or showering (OR=3.7; CI:1.3-10.3) and hours spent in one's own yard (OR=1.2, CI:1.1-1.3). Nineteen participants found ticks on multiple days, more than expected assuming independence (p<0.001). Participants who found ticks on multiple days did not spend more time outdoors but were significantly more likely to be male than those finding ticks on a single day (p<0.03). Our findings suggest that most tick exposures in the study area occurred on private property controlled by the respective homeowner. Interventions that target private yards are a logical focus for prevention efforts.

Initial implementation and evaluation of a Hepatitis C treatment clinical decision support system (CDSS): a nurse practitioner-driven quality improvement initiative.

BACKGROUND: Clinician compliance with clinical guidelines in the treatment of patients with Hepatitis C (HCV) has been reported to be as low as 18.5%. Treatment is complex and patient compliance is often inconsistent thus, active clinician surveillance and support is essential to successful outcomes. A clinical decision support system (CDSS) embedded within an electronic health record can provide reminders, summarize key data, and facilitate coordination of care. To date, the literature is bereft of information describing the implementation and evaluation of a CDSS to support HCV treatment. OBJECTIVE: The purpose of this case report is to describe the design, implementation, and initial evaluation of an HCV-specific CDSS while piloting data collection metrics and methods to be used in a larger study across multiple practices. METHODS: The case report describes the design and implementation processes with preliminary reporting on impact of the CDSS on quality indicator completion by comparing the pre-CDSS group to the post-CDSS group. RESULTS: The CDSS was successfully designed and implemented using an iterative, collaborative process. Pilot testing of the clinical outcomes of the CDSS revealed high rates of quality indicator completion in both the pre- and post-CDSS; although the post-CDSS group received a higher frequency of reminders (4.25 per patient) than the pre-CDSS group (.25 per patient). CONCLUSIONS: This case report documents the processes used to successfully design and implement an HCV CDSS. While the small sample size precludes generalizability of findings, results did positively demonstrate the feasibility of comparing quality indicator completion rates pre-CDSS and post-CDSS. It is recommended that future studies include a larger sample size across multiple providers with expanded outcomes measures related to patient outcomes, staff satisfaction with the CDSS, and time studies to evaluate efficiency and cost effectiveness of the CDSS.

Functional circuitry of a unique cerebellar specialization: the valvula cerebelli of a mormyrid fish.

The valvula cerebelli of the mormyrid electric fish is a useful site for the study of cerebellar function. The valvula forms a part of the electrosensory-electromotor system of this fish, a system that offers many possibilities for the study of sensory-motor integration. The valvula also has a number of histological features not present in mammals which facilitate investigation of cerebellar circuitry and its plasticity. This initial study characterizes the basic physiology and pharmacology of cells in the valvula using an in vitro slice preparation. Intrinsic properties and synaptic responses of Purkinje cells and other cell types were examined. We found that Purkinje cells fire a small narrow Na(+) spike and a large broad Ca(2+) spike, generated in the axon initial segment and dendritic-soma region, respectively. Purkinje cells respond to parallel fiber inputs with graded excitatory postsynaptic potentials (EPSPs) and to climbing fiber inputs with all-or-none EPSPs. Efferent cells, Golgi cells, and deep stellate cells all fire a single type of large narrow spike and respond only to parallel fiber inputs. Both parallel fiber and climbing fiber responses in Purkinje cells appear to be entirely mediated by AMPA-type glutamate receptors, whereas parallel fiber responses in efferent cells and stellate cells include AMPA and NMDA components. In addition, a strong synaptic inhibition was uncovered in both Purkinje cells and efferent cells in response to the focal stimulation of parallel fibers. Dual cell recordings indicate that deep stellate cells contribute at least partially to this inhibition. We conclude that despite its unique histology, the local functional circuitry of the mormyrid valvula cerebelli is largely similar to that of the mammalian cerebellum. Thus, what is learned concerning the functioning of the mormyrid valvula cerebelli may be expected to be informative about cerebellar function in general.

Electrophysiological measurements and analysis of nociception in human infants.

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns. The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord. This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.

Quantitative fit assessment of tibial nail designs using 3D computer modelling.

Intramedullary nailing is the standard fixation method for displaced diaphyseal fractures of the tibia in adults. The bends in modern tibial nails allow for an easier insertion, enhance the 'bone-nail construct' stability, and reduce axial malalignments of the main fragments. Anecdotal clinical evidence indicates that current nail designs do not fit optimally for patients of Asian origin. The aim of this study was to develop a method to quantitatively assess the anatomical fitting of two different nail designs for Asian tibiae by utilising 3D computer modelling. We used 3D models of two different tibial nail designs (ETN (Expert Tibia Nail) and ETN-Proximal-Bend, Synthes), and 20 CT-based 3D cortex models of Japanese cadaver tibiae. With the aid of computer graphical methods, the 3D nail models were positioned inside the medullary cavity of the intact 3D tibia models. The anatomical fitting between nail and bone was assessed by the extent of the nail protrusion from the medullary cavity into the cortical bone, in a real bone this might lead to axial malalignments of the main fragments. The fitting was quantified in terms of the total surface area, and the maximum distance by which the nail was protruding into the cortex of the virtual bone model. In all 20 bone models, the total area of the nail protruding from the medullary cavity was smaller for the ETN-Proximal-Bend (average 540 mm(2)) compared to the ETN (average 1044 mm(2)). Also, the maximum distance of the nail protruding from the medullary cavity was smaller for the ETN-Proximal-Bend (average 1.2mm) compared to the ETN (average 2.7 mm). The differences were statistically significant (p<0.05) for both the total surface area and the maximum distance measurements. By utilising computer graphical methods it was possible to conduct a quantitative fit assessment of different nail designs. The ETN-Proximal-Bend shows a statistical significantly better intramedullary fit with less cortical protrusion than the original ETN. In addition to the application in implant design, the developed method could potentially be suitable for pre-operative planning enabling the surgeon to choose the most appropriate nail design for a particular patient.

Quantification of the genetic component of basal C-reactive protein expression in SLE nuclear families.

C-reactive protein (CRP) is a heritable acute-phase plasma protein also expressed at low, basal, levels in healthy individuals. Elevated basal CRP has been associated with increased cardiovascular risk, while CRP dysregulation may be a feature of systemic lupus erythematosus (SLE). In this cohort of 496 Caucasian SLE families we estimated basal CRP heritability, h(2)= 27.7%. We typed a dense map of CRP single nucleotide polymorphisms (SNPs) and found that seven were associated with basal CRP using both a regression approach and an orthogonal family-based test (P = 0.001-0.011), as were haplotypes carrying the minor allele of these SNPs. SNPs in the interleukin-1beta and interleukin-6 genes were associated with basal CRP. No association was seen between CRP genotype and SLE. Using a variance components approach we estimated that the CRP genotype accounted for only 15% of the total genetic component of basal CRP variation, perhaps explaining the limited evidence of association between CRP and disease. Most of the genetic determinants of basal CRP variation therefore remain unknown. Multiple genes may be involved and identifying them will provide an insight into pathways regulating CRP expression, highlight potential cardiovascular disease and SLE candidates and improve the ability of basal CRP to predict cardiovascular risk.

ESR or CRP? A comparison of their clinical utility.

OBJECTIVE: To review the normal reference values for erythrocyte sedimentation rate (ESR) and the significance of high values in the elderly, to re-examine the correlation, if any, between ESR and C-reactive protein (CRP) and to compare their utility and limitations for both health screening and clinical management of patients. METHODS: CRP and ESR were measured in 295 blood samples from male and female subjects in whom their family doctors had found no clinically significant symptoms nor abnormal physical sign and in whom all other pathology tests gave normal results. None had been hospitalised during at least a six-week period prior to the study. RESULTS: The results showed a mean ESR of 10 mm/1 h (range 0-25) in both males and females below the age of 40 yrs; this increased with age, to a mean of 18 mm (range 0-35) by 60 yrs in both men and women. In the CRP test, 95% of the samples in the >40 yrs group had CRP range of 0-18 mg/l compared with 0-10 mg/l in the younger subjects. The distribution plot of CRP results showed a left skew with mode at about 2 mg/l, whereas the equivalent ESR distribution shows a broad plateau with less skew. Thus, there was more overlapping of the numerical values for ESR and CRP in subjects younger than 40 yrs, as compared with those over 40 yrs old in whom the two sets of measurements were well separated. The relative utility of the two tests in clinical management of patients was also discussed. Different rates of increase and subsequent fall in the test results were shown over several weeks on a patient with an acute infection. Initially, both tests were increased, but after antibiotic therapy the CRP returned to normal indicating that remission had occurred, whereas the ESR remained high, indicating persistence of the infection. A subsequent dramatic increase in CRP to 180 mg/l confirmed the re-infection that had been indicated earlier by the ESR. After further antibiotic therapy CRP fell to normal, followed later by a slower reduction in ESR to a normal value for the patient's age. CONCLUSION: This study confirms that after the age of 40, there is an age-related elevation of ESR, increasing steadily, especially after age 60 yrs. CRP is also affected by age, but to a much less extent. ESR and CRP appear to be equally useful and reliable as a screening test. Accordingly, in deciding which test should be carried out account must be taken of their relative convenience and cost. However, when required as a clinical test in the management of patients with specific diseases both tests should be carried out in tandem.

Activation of a sensorimotor pathway in response to a water temperature drop in a teleost fish.

When common carp, Cyprinus carpio L., experience a rapid temperature drop, the cerebral blood volume is strongly reduced to dampen the temperature drop in the brain. Simultaneously, the preoptic area and pituitary gland are activated to launch whole-body adaptive responses. However, the preferred reaction of fish to a temperature change is an escape reaction, which implies activation of a sensorimotor pathway. Here, we used blood oxygenation level-dependent (BOLD)- and cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) to identify a sensorimotor pathway, during a 10 degrees C temperature drop in common carp. Transient activation was observed in the region where the sensory root of the trigeminal nerve enters the brain, and in the valvula cerebelli. In both regions, metabolic activity increased (increased deoxyhemoglobin content demonstrated by a decreased BOLD signal) within 30 s after the onset of the temperature drop, peaked after 2-3 min, and then decreased, even though the temperature continued to drop for another 2 min. These brain structures appear to respond to temperature change, rather than to the absolute temperature. Thus, during a temperature drop, the sensorimotor pathway consisting of the trigeminal nerve, the primary sensory trigeminal nucleus, the valvula cerebelli and some motornuclei, is active, in line with perception of temperature change in the buccal cavity, leading to motor activity for escape. This pathway operates in parallel to an acclimation pathway, which involves the preoptic area to pituitary gland pathway.

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain.

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside.

Three-dimensional whole-head optical tomography of passive motor evoked responses in the neonate.

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation.

AIM: To determine cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation during the first three days of life. Low cerebral blood flow has been associated with both intra-ventricular haemorrhage and periventricular leucomalacia. It is well established that cerebral blood flow increases over the first three days of life in extremely preterm infants who are conventionally ventilated with intermittent positive pressure ventilation. However, there is no information about cerebral blood flow in preterm babies undergoing high-frequency oscillatory ventilation. In addition, there are concerns that high-frequency oscillatory ventilation may be associated with an increased incidence of intra-ventricular haemorrhage in premature infants. METHODS: Thirteen appropriately grown, preterm infants of less than 28 wk gestation who were admitted to the neonatal unit at University College Hospital, London were studied using near infrared spectroscopy. Left ventricular output and right ventricular output were assessed echocardiographically. RESULTS: Extremely preterm infants undergoing high-frequency oscillatory ventilation have remarkably low cerebral blood flow in the first 12 h of life, median 6.7 (range 4.4-11) mls. 100 g(-1) min(-1) followed by an increase over the subsequent three days. Left ventricular output also increased over the first three days of life, whereas right ventricular output showed no clear relationship with time. Despite low cerebral blood flow only one infant had evidence of major cerebral injury. CONCLUSION: Cerebral blood flow is extremely low in this group of preterm babies. Despite this extremely low cerebral blood flow, the clinical outcome is good. There was an increase in cerebral blood flow and a corresponding increase in left ventricular output over the first few days of life.

Early-onset neonatal sepsis in the era of group B streptococcal prevention.

OBJECTIVE: To determine whether intrapartum antibiotic prophylaxis for neonatal group B streptococcal (GBS) disease has resulted in an increased rate of non-GBS or antibiotic-resistant early-onset invasive neonatal disease. METHODS: Maternal and infant chart review of all infants with bacteria other than GBS isolated from blood or spinal fluid in 1996 through 1999 in 19 hospitals (representing 81% of in-state births to state residents) throughout Connecticut. Suspected cases were identified through clinical microbiology laboratory records or through International Classification of Diseases, Ninth Revision codes when microbiology records were incomplete. RESULTS: Ninety-four cases of non-GBS early-onset sepsis or meningitis were detected between 1996 and 1999. The rate of GBS-related early-onset infection (days 0-6 of life) dropped from 0.61/1000 to 0.23/1000 births, but the annual rate of non-GBS sepsis remained steady, ranging from 0.65 to 0.68/1000 during the surveillance period. There was an increase in the proportion of Escherichia coli infections that were ampicillin resistant between 1996 and 1998, but the proportion decreased. in 1999 CONCLUSION: There was no increase in the incidence of non-GBS early-onset neonatal infections between 1996 and 1999. Fluctuations in the annual incidence of E coli infections, including ampicillin-resistant infections, suggest the need for continuation of surveillance in Connecticut and expansion to monitor larger populations.

Retrospective validation of a surveillance system for unexplained illness and death: New Haven County, Connecticut.

OBJECTIVES: This study investigated retrospective validation of a prospective surveillance system for unexplained illness and death due to possibly infectious causes. METHODS: A computerized search of hospital discharge data identified patients with potential unexplained illness and death due to possibly infectious causes. Medical records for such patients were reviewed for satisfaction of study criteria. Cases identified retrospectively were combined with prospectively identified cases to form a reference population against which sensitivity could be measured. RESULTS: Retrospective validation was 41% sensitive, whereas prospective surveillance was 73% sensitive. The annual incidence of unexplained illness and death due to possibly infectious causes during 1995 and 1996 in the study county was conservatively estimated to range from 2.7 to 6.2 per 100,000 residents aged 1 to 49 years. CONCLUSIONS: Active prospective surveillance for unexplained illness and death due to possibly infectious causes is more sensitive than retrospective surveillance conducted through a published list of indicator codes. However, retrospective surveillance can be a feasible and much less labor-intensive alternative to active prospective surveillance when the latter is not possible or desired.

Breastfeeding in the workplace.

More than 50% of women of reproductive age are employed, and most return to work post partum at a time when exclusive breastfeeding is the ideal. Public health efforts target a goal of increased breastfeeding initiation and duration rates. To be successful at integrating the roles of breastfeeding mother and employee, women need practical advice, the encouragement and support of health care providers, and societal and workplace support. This article discusses the current state of employed breastfeeding women and provides practical guidelines for assisting women to be successful at meeting breastfeeding goals.

MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer.

A set of 90 nonpolypotic colon cancer families in which germ-line mutations of MSH2 and MLH1 had been excluded were screened for mutations in two additional DNA mismatch repair genes, MSH6 and MSH3. Kindreds fulfilling and not fulfilling the Amsterdam I criteria, showing early and late onset colorectal (and other) cancers, and having microsatellite stable and unstable tumors were included. Two partly parallel approaches were used: genetic linkage analysis (19 large families) and the protein truncation test (85, mostly smaller, families). Whereas MSH3 was not involved in any family, a large Amsterdam-positive, late-onset family showed a novel germ-line mutation in MSH6 (deletion of CT at nucleotide 3052 in exon 4). The mutation was identified through genetic linkage (multipoint lod score 2.4) and subsequent sequencing of MSH6. Furthermore, the entire MSH6 gene was sequenced exon by exon in families with frameshift mutations in the (C)8 tract in tumors, previously suggested as a predictor of MSH6 germ-line mutations; no mutations were found. We conclude that germ-line involvement of MSH6 and MSH3 is rare and that other genes are likely to account for a majority of MSH2-, MLH1-mutation negative families with nonpolypotic colon cancer.