An Exploration of Sleep and Family Factors in Young Children at Familial Risk for ADHD.

Objective: The aim of the current study was to examine relations between sleep problems and family factors and early markers of ADHD in young children with and without a familial risk for ADHD.Methods: Differences in sleep behavior and family functioning in children under 6 years with (n = 72) and without (n = 139) a familial risk for ADHD were investigated. The influence of family and sleep factors on the development of early temperament markers of ADHD (effortful control and negative affect) was explored. Parents/caregivers completed questionnaires on family functioning, child sleep behavior, and general regulatory behaviors.Results: A significant difference was observed between high-risk and low-risk groups for family functioning in the infant/toddler (<3 years) and preschool (>3 years) cohorts. Parents of infants/toddlers in the high-risk group reported poorer infant sleep. However, there were no sleep differences reported for the preschool cohort. Family functioning was found to predict effortful control, while sleep quality predicted negative affect.Conclusion: The results of this study highlight potential family and sleep issues for young children with a familial history of ADHD and the potential influence of these factors on early temperament markers of ADHD. Future research should explore these relations further in order to better establish whether early sleep and family interventions could mitigate later ADHD symptomatology.

Higher rate of complications with uncemented compared to cemented total hip arthroplasty for displaced intracapsular hip fractures: A randomised controlled trial of 50 patients.

BACKGROUND: The primary aim of this study was to compare the functional outcome of uncemented with cemented total hip arthroplasty (THA) for displaced intracapsular hip fractures. The secondary aims were to assess length of surgery, blood loss, complications and revision rate between the two groups. METHODS: A prospective double-blind randomised control trial was conducted. Fifty patients with an intracapsular hip fracture meeting the inclusion criteria were randomised to either an uncemented (n = 25) or cemented (n = 25) THA. There were no differences (p > 0.45) in age, gender, health status or preinjury hip function between the groups. The Oxford hip score (OHS), Harris Hip score (HHS), EuroQol 5-dimensional (EQ5D), timed get up-and-go (TUG), pain and patient satisfaction were used to assess outcome. These were assessed at 4, 12 and 72 months after surgery, apart from the TUG which as only assessed as 6 months. RESULTS: The study was terminated early due to the significantly (n = 8, p = 0.004) higher rate of intraoperative complications in the uncemented group: three fractures of the proximal femur and five conversions to a cemented acetabular component. There were no significant (p ≥ 0.09) differences in the functional measures (OHS, HSS, EQ5D, TUG and pain) or patient satisfaction between the groups. There was no difference in operative time (p = 0.75) or blood loss (p = 0.66) between the groups. There were two early revisions prior to 3 months post-operatively in the uncemented group and none in the cemented group, but this was not significant (log rank p = 0.16). CONCLUSION: There was a high rate of intraoperative complications, which may be due to poor bone quality in this patient group. There were no ergonomic or functional advantages demonstrated between uncemented and cemented THA. Cemented THA should remain as the preferred choice for the treatment of intracapsular hip fractures for patients that meet the criteria for this procedure.

Differentiation of the 50B11 dorsal ganglion cells into NGF and GDNF responsive nociceptor subtypes.

The embryonic rat dorsal root ganglion (DRG) neuron-derived 50B11 cell line is a promising sensory neuron model expressing markers characteristic of NGF and GDNF-dependent C-fibre nociceptors. Whether these cells have the capacity to develop into distinct nociceptive subtypes based on NGF- or GDNF-dependence has not been investigated. Here we show that by augmenting forskolin (FSK) and growth factor supplementation with NGF or GDNF, 50B11 cultures can be driven to acquire differential functional responses to common nociceptive agonists capsaicin and ATP respectively. In addition, to previous studies, we also demonstrate that a differentiated neuronal phenotype can be maintained for up to 7 days. Western blot analysis of nociceptive marker proteins further demonstrates that the 50B11 cells partially recapitulate the functional phenotypes of classical NGF-dependent (peptidergic) and GDNF-dependent (non-peptidergic) neuronal subtypes described in DRGs. Further, 50B11 cells differentiated with NGF/FSK, but not GDNF/FSK, show sensitization to acute prostaglandin E2 treatment. Finally, RNA-Seq analysis confirms that differentiation with NGF/FSK or GDNF/FSK produces two 50B11 cell subtypes with distinct transcriptome expression profiles. Gene ontology comparison of the two subtypes of differentiated 50B11 cells to rodent DRG neurons studies shows significant overlap in matching or partially matching categories. This transcriptomic analysis will aid future suitability assessment of the 50B11 cells as a high-throughput nociceptor model for a broad range of experimental applications. In conclusion, this study shows that the 50B11 cell line is capable of partially recapitulating features of two distinct types of embryonic NGF and GDNF-dependent nociceptor-like cells.

Avoiding, diagnosing and treating well leg compartment syndrome after pelvic surgery.

BACKGROUND: Patients undergoing prolonged pelvic surgery may develop compartment syndrome of one or both lower limbs in the absence of direct trauma or pre-existing vascular disease (well leg compartment syndrome). This condition may have devastating consequences for postoperative recovery, including loss of life or limb, and irreversible disability. METHODS: These guidelines represent the collaboration of a multidisciplinary group of colorectal, vascular and orthopaedic surgeons, acting on behalf of their specialty associations in the UK and Ireland. A systematic analysis of the available peer-reviewed literature was undertaken to provide an evidence base from which these guidelines were developed. RESULTS: These guidelines encompass the risk factors (both patient- and procedure-related), diagnosis and management of the condition. Key recommendations for the adoption of perioperative strategies to facilitate prevention and effective treatment of well leg compartment syndrome are presented. CONCLUSION: All surgeons who carry out abdominopelvic surgical procedures should be aware of well leg compartment syndrome, and instigate policies within their own institution to reduce the risk of this potentially life-changing complication.

Allosensitization Following Bone Graft.

It is recognized that patients may become sensitized to donor-specific HLA antigens as a result of previous antigenic exposures, classically through previous transplantation, pregnancy, or blood transfusion. We present an unusual case of a patient who unexpectedly developed a range of anti-HLA antibodies following orthopedic surgery where a bone graft was deployed intraoperatively. We describe the case of a 52-year-old man awaiting a renal transplantation, undergoing elective orthopedic surgery requiring a small-volume bone graft. His postoperative antibody profile was found to be substantially changed compared to his previous negative samples, with the presence of HLA-DR, DQ, and DP specificities, at levels that would be likely to give a positive flow cytometry crossmatch and therefore according to local procedures required listing as unacceptable antigens for organ allocation. We perform a literature review of all previous cases of allosensitization following bone graft. This case is the first to demonstrate allosensitization following minor surgery with ;low-volume bone graft. Previous evidence is very limited and pertains only to massive osteochondral surgery for trauma or malignancy, and is confounded by potential concomitant blood transfusion. Clinicians should be aware of the risk of allosensitization where bone grafts are used.

Number fields and function fields: coalescences, contrasts and emerging applications.

The similarity between the density of the primes and the density of irreducible polynomials defined over a finite field of q elements was first observed by Gauss. Since then, many other analogies have been uncovered between arithmetic in number fields and in function fields defined over a finite field. Although an active area of interaction for the past half century at least, the language and techniques used in analytic number theory and in the function field setting are quite different, and this has frustrated interchanges between the two areas. This situation is currently changing, and there has been substantial progress on a number of problems stimulated by bringing together ideas from each field. We here introduce the papers published in this Theo Murphy meeting issue, where some of the recent developments are explained.

Rapid profiling of enteric coated drug delivery spheres via broadband acoustic resonance dissolution spectroscopy (BARDS).

There is an increased trend towards the use of drug and enteric coated sugar spheres for controlled oral delivery of active pharmaceutical ingredients (API). This trend is driven by increased efficacy and ease of formulation of different dosage levels. However, difficulties exist in determining the thickness of drug and enteric coatings in a time efficient manner during manufacture, quality assurance and stability testing. The thickness of the coating determines the dosage of the API and the thickness of the enteric coating determines the release rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising the enteric coating thickness and the raw materials used in their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically due to associated changes in the speed of sound in solution. It is demonstrated how core delivery sugar spheres have unique acoustic spectra attributable to the mean size distribution of the spheres. A steady state acoustic lag time is associated with the disintegration of the enteric coating, in basic solution. This lag time can be manipulated by varying the concentration of the base which affects the rate at which the coating dissolves. It is anticipated that the thickness/loading of the spheres can be estimated from the lag time.

Cerebral Hirano-like bodies in an alpaca (Vicugna pacos): histologic and ultrastructural characterization.

A 14-year-old female alpaca (Vicugna pacos) was presented with a 1-week history of lethargy and anorexia and a 2-day history of recumbency, trembling, and hypothermia. There were no significant gross findings on postmortem examination. Hematoxylin and eosin-stained sections of brain demonstrated the presence of intracytoplasmic crystalline eosinophilic rod-shaped inclusions, mainly in the hippocampal pyramidal cells. Immunohistochemical staining for synuclein, tau protein, ubiquitin, and smooth muscle actin was negative. All inclusions were positive with phosphotungstic acid hematoxylin. Ultrastructurally, the inclusions were multilamellar and filamentous with longitudinal herringbone pattern and cross-sectional latticelike structure. The combination of hematoxylin and eosin appearance, special stains, immunostaining, and ultrastructural findings was consistent with Hirano-like bodies. The Hirano-like bodies were highly unlikely to be the cause of the neurologic signs experienced by this alpaca. To the authors' knowledge, this is the first report of spontaneous cerebral Hirano-like bodies in an alpaca.

The surgical treatment of knee stiffness following anterior cruciate ligament reconstruction.

Knee stiffness following anterior cruciate ligament (ACL) reconstruction remains a common complication, which can substantially impair knee function. The aim of this study was to assess the effectiveness of arthroscopic arthrolysis, in conjunction with manipulation under anaesthetic (MUA), in treating stiffness post-ACL reconstruction. We reviewed the records of 18 patients who underwent arthroscopic arthrolysis to treat established stiffness following primary isolated ACL reconstruction. Eight of these patients underwent concomitant MUA at time of arthrolysis. The median time between reconstruction and arthrolysis was nine months. Seven patients had arthrolysis performed within eight months of reconstruction, while 11 patients underwent arthrolysis greater than eight months postreconstruction. Following arthrolysis, the mean extension loss improved from 7° to 1°. In patients with mild extension stiffness (prearthrolysis extension deficits <10°), the mean improvement to extension was 3°. In patients with severe extension stiffness (prearthrolysis extension deficit ≥10°), the mean improvement to extension was 10°. Arthroscopic arthrolysis was significantly more effective in restoring extension loss if carried out within eight months of the primary reconstruction (P < 0.03). In the patients who underwent MUA at time of arthrolysis, the mean flexion loss improved from 16° to 4°. In conclusion, arthroscopic arthrolysis, in conjunction with MUA, is an effective treatment for knee stiffness post-ACL reconstruction but ideally should be carried out within eight months.

Moments of Moments and Branching Random Walks.

We calculate, for a branching random walk X n ( l ) to a leaf l at depth n on a binary tree, the positive integer moments of the random variable 1 2 n ∑ l = 1 2 n e 2 ß X n ( l ) , for ß ∈ R . We obtain explicit formulae for the first few moments for finite n. In the limit n → ∞ , our expression coincides with recent conjectures and results concerning the moments of moments of characteristic polynomials of random unitary matrices, supporting the idea that these two problems, which both fall into the class of logarithmically correlated Gaussian random fields, are related to each other.

Sensory modulation and negative affect in children at familial risk of ADHD.

BACKGROUND/AIMS: Sensory modulation difficulties are commonly reported in patients with ADHD, however there has been little focus on the development of these difficulties in young children at a higher risk of later ADHD diagnosis. This study investigated whether children with a familial history of ADHD show greater sensory modulation difficulties. We also explored whether sensory modulation was linked to negative affectivity, which has been highlighted as a potential early marker of ADHD. METHODS: Parents of children under 6 years with a family history of ADHD (n = 65) and no family history (n = 122) completed questionnaires on sensory modulation and temperament. RESULTS: Children from families with ADHD were reported to display extreme patterns of hyperresponsiveness and hyporesponsiveness, relative to controls. No differences emerged for the sensory seeking domain. Some children within the high-risk group reported high scores across all three sensory modulation patterns. Regression analysis revealed that hyperresponsiveness predicted higher levels of negative affect. CONCLUSIONS/IMPLICATIONS: This study is the first to report greater sensory modulation difficulties in children at familial risk of ADHD. Future research should establish whether children with sensory modulation and temperament difficulties in early childhood are more vulnerable to developing ADHD.

Fracture nonunion in long bones: A literature review of risk factors and surgical management.

Nonunion following a long bone fracture causes considerable morbidity when it occurs. Risk factors depend on specific fractures but there is a complex interplay of injury severity, comorbidities, patient medication and infection. The majority of nonunions occur after long bone fractures with the tibia, femur, forearm, humerus and clavicle predominating. Despite interest in the biological augmentation of fracture healing, the majority of nonunions can be effectively managed with conventional surgical techniques. In this review we present a review of risk factors for nonunion and the outcome following surgical management.

Monitoring of fracture healing. Update on current and future imaging modalities to predict union.

Fracture nonunion causes considerable patient morbidity and an associated burden to society. Traditional reliance on radiographs to monitor union has limitations as bridging callus of long bone fractures can take three or more months to occur. Computed Tomographic (CT) scanning is becoming increasingly popular and can evaluate bridging callus in the late stages of healing to confirm union. The use of dynamic contrast enhanced Magnetic Resonance Imaging (MRI) and advances in nuclear imaging may yield benefits in the assessment of the infected nonunion. Emerging evidence supports the use of ultrasound to detect bridging callus prior to radiographic confirmation and it may be of use to predict patients at high risk of nonunion. This paper is part of a Supplement supported by The Osteosynthesis and Trauma Care Foundation (OTCF).

Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae.

The global rate of heavy metal pollution is rapidly increasing in various habitats. Anopheles malaria vector species (Diptera: Culicidae) appear to tolerate many aquatic habitats with metal pollutants, despite their normal proclivity for 'clean' water (i.e. low levels of organic matter). Investigations were conducted to establish whether there are biological costs for tolerance to heavy metals in Anopheles gambiae Giles sensu stricto and to assess the potential impact of heavy metal pollution on mosquito ecology. Anopheles gambiae s.s. were selected for cadmium, copper or lead tolerance through chronic exposure of immature stages to solutions of the metals for three successive generations. Biological costs were assessed in the fourth generation by horizontal life table analysis. Tolerance in larvae to cadmium (as cadmium chloride, CdCl(2)), copper [as copper II nitrate hydrate, Cu(NO(3))(2) 2.5 H(2)O] and lead [as lead II nitrate, Pb(NO(3))(2)], monitored by changes in LC(50) concentrations of the metals, changed from 6.07 microg/L, 12.42 microg/L and 493.32 microg/L to 4.45 microg/L, 25.02 microg/L and 516.69 microg/L, respectively, after three generations of exposure. The metal-selected strains had a significantly lower magnitude of egg viability, larval and pupal survivorship, adult emergence, fecundity and net reproductive rate than the control strain. The population doubling times were significantly longer and the instantaneous birth rates lower in most metal-selected strains relative to the control strain. Our results suggest that although An. gambiae s.s. displays the potential to develop tolerance to heavy metals, particularly copper, this may occur at a significant biological cost, which can adversely affect its ecological fitness.

Dating and context of three middle stone age sites with bone points in the Upper Semliki Valley, Zaire.

The extent to which the earliest anatomically modern humans in Africa exhibited behavioral and cognitive traits typical of Homo sapiens sapiens is controversial. In eastern Zaire, archaeological sites with bone points have yielded dates older than 89(-15)+22 thousand years ago by several techniques. These include electron spin resonance, thermoluminescence, optically stimulated luminescence, uranium series, and amino acid racemization. Faunal and stratigraphic data are consistent with this age.

Older age and female gender are independent predictors of early conversion to total knee arthroplasty after high tibial osteotomy.

BACKGROUND: The primary aim was to assess survival of opening wedge high tibial osteotomy (HTO) for medial compartment osteoarthritis. The secondary aim was to identify independent predictors of early conversion to total knee arthroplasty (TKA). METHODS: During the 18-year period (1994-2011) 111 opening wedge HTO were performed at the study centre. Mean age was 45 years (range 18-68) and the majority male (84%). Mean follow-up was 12 (range six to 21) years. Failure was defined as conversion to TKA. Kaplan-Meier, Cox regression and receiver operating curve (ROC) analyses were performed. RESULTS: Forty (36.0%) HTO failed at a mean of 6.3 years (range one to 15). By Kaplan-Meier analysis, the five-year survival rate was 84% (95% confidence interval (CI) 82.6-85.4), 10-year rate 65% (95% CI 63.5-66.5) and 15-year rate 55% (95% CI 53.3-56.7). Cox regression analysis identified older age (hazard ratio (HR) 1.07 for each additional year, 95% CI 1.03-1.11, p b 0.001) and female gender (HR 2.37, 95% CI 1.06-5.33, p = 0.04) as independent predictors of failure. ROC analysis identified a threshold age of 47 years above which the risk of failure increased significantly (area under curve 0.72, 95% CI 0.62-0.81, p b 0.001). Cox regression analysis, adjusting for covariates, identified a significantly greater (HR 2.49, 95% CI 1.26-4.91, p = 0.01) risk of failure in patients aged 47 years old or more. CONCLUSION: The risk of early conversion to TKA is significantly increased in females and those older than 47. These risk factors should be considered pre-operatively when planning intervention for isolated medial compartment osteoarthritis.

Forage fish and polycyclic aromatic compounds in the Fort McMurray oil sands area: Body burden comparisons with environmental distributions and consumption guidelines.

The Fort McMurray region in northeastern Alberta (Canada) is rich in natural sources of polycyclic aromatic compounds (PACs) from exposed bitumen beds; anthropogenic sources are being released with increased oil sands industry expansion. Here we report on investigations of PACs (47 compounds) in three species of forage fish collected during the 2012-2013 Joint Oil Sands Monitoring Program (JOSMP) fish health investigations and compare results with PAC data for sediment and water collected under JOSMP and earlier programs. PAC concentrations in sediments varied three orders in magnitude and were highest at downstream tributary mouths, which flowed through the exposed McMurray Formation, and along reaches of the Athabasca River where the formation was exposed. PAC concentrations in water were less variable but with higher concentrations near exposed bitumen beds. Forage fish exhibited the weakest spatial gradients in ΣPACs concentration, which averaged 102 ±â€¯32 ng/g in trout-perch from the Athabasca River, 125 ±â€¯22 ng/g in lake chub from the Ells River, and 278 ±â€¯267 ng/g in slimy sculpin from the Steepbank, Firebag, and Dunkirk Rivers. Low-molecular weight compounds, particularly naphthalenes and fluorenes, dominated fish PACs. Phenanthrenes occurred in greater percent composition in fish caught in areas where PAC concentrations in sediments were higher due to the proximity of bitumen sources than in other areas. Dibenzothiophene, a major component of bitumen PAC, was a minor component of fish ΣPACs. Forage fish PAC concentrations were below fish consumption guidelines established by the European Commission (2011) and for the reopening of the commercial fisheries closed by the Deepwater Horizon oil spill. PAC concentrations in forage fish were similar to concentrations observed in many other studies (fish market surveys, estuaries, and marine waters) and lower than in fish sampled from highly impacted areas (near refineries, harbors, and other industrialized areas).

Patient-reported functional outcomes and health-related quality of life following fractures of the talus.

INTRODUCTION: The primary aim of this study was to investigate patient-reported outcomes following talar fractures. Secondary aims were to investigate health-related quality of life and to determine whether it is influenced by functional outcome. MATERIALS AND METHODS: This retrospective study identified 56 talar fractures over eight years. Patients were contacted by post and the Olerud and Molander score (OMS), Manchester-Oxford Foot and Ankle scores (MOXFQ) and Euroqol-5D-3L collected. RESULTS: The mean age was 35.2 years (range 13-78 years). There were four cases (7.1%) of avascular necrosis and one (1.8%) non-union occurred. Data from patient-reported outcome measures were available for 42 patients (75.0%) with a median follow-up of 67.1 months (range 23.2-111.8 months). Mean OMS was 60.0 (standard deviation ± 29.51) and median MOXFQ was 30.33 (interquartile range 47.13). Median Euroqol-5D-3L index was 0.74 (interquartile range 0.213) and median Euroqol-5D-3L visual analogue score was 80 (interquartile range 21). Older age, open fractures, multiple injuries and subsequent avascular necrosis were associated with worse patient-reported outcomes (P < 0.05), with older age, avascular necrosis and open fractures found to be independent predictors of poor OMS, and avascular necrosis and open fractures independently predicting MOXFQ score on regression analysis (P < 0.05). Poor self-reported function, measured by OMS and MOXFQ, correlated with worse health-related quality of life as measured by the Euroqol-5D-3L index (OMS: r = 0.764, P < 0.001; MOXFQ: r = 0.824, P < 0.001) and visual analogue score (OMS: r = 0.450, P = 0.003; MOXFQ: r=0.559, P < 0.001). CONCLUSIONS: Older age, avascular necrosis and open fractures predict poorer functional outcomes following talar fractures. Patients with worse limb-specific functional outcomes are more likely to have a worse perception of health-related quality of life.

Portal vein thrombosis in cats: 6 cases (2001-2006).

BACKGROUND: Portal vein thrombosis (PVT) in cats is sparsely reported. PURPOSE OF STUDY: To evaluate the clinical signs and diseases associated with PVT in cats. ANIMALS: 6 client-owned cats. METHODS: Medical records for cats with a portal vein thrombus diagnosed on abdominal ultrasound or at necropsy were reviewed. Signalment, historical data, underlying disorders, clinical findings, clinicopathologic and histopathologic data, diagnostic imaging findings, treatment, and outcome were recorded. RESULTS: All 6 cats identified with PVT also had hepatic disease. Evidence of a congenital portosystemic shunt was present in 3/6 cats. Two cats had primary or metastatic hepatic neoplasia. One cat had acute cholangitis, acute pancreatitis, and locally extensive acute centrilobular hepatic necrosis. Two cats were suspected to have acute thrombi and 4 cats had chronic thrombi. CONCLUSION AND CLINICAL SIGNIFICANCE: PVT might be an important concurrent finding in cats with hepatic disease.