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1.  Social communication deficits: Specific associations with Social Anxiety Disorder 
Social communication deficits are prevalent amongst children with anxiety disorders; however whether they are over-represented specifically among children with Social Anxiety Disorder has not been examined. This study set out to examine social communication deficits among children with Social Anxiety Disorder in comparison to children with other forms of anxiety disorder.
Parents of 404 children with a diagnosed anxiety disorder completed the Social Communication Questionnaire (SCQ; Rutter, M., Bailey, A., Lord, C., 2003. The Social Communication Questionnaire – Manual. Western Psychological Services, Los Angeles, CA). Children with a diagnosis of Social Anxiety Disorder (n=262) and anxious children without Social Anxiety Disorder (n=142) were compared on SCQ total and subscale scores and the frequency of participants scoring above clinical cut-offs.
Children with Social Anxiety Disorder scored significantly higher than anxious children without Social Anxiety Disorder on the SCQ total (t(352)=4.85, p<.001, d=.55, r=.27), Reciprocal Social Interaction (t(351)=4.73, p<.001, d=.55, r=.27), communication (t(344)=3.62, p<.001, d=.43, r=.21) and repetitive, restrictive and stereotyped behaviors subscales (t(353)=3.15, p=.002, d=.37, r=.18). Furthermore, children with Social Anxiety Disorder were three times more likely to score above clinical cut-offs.
The participants were a relatively affluent group of predominantly non-minority status. The social communication difficulties measure relied on parental report which could be influenced by extraneous factors.
Treatments for Social Anxiety Disorder may benefit from a specific focus on developing social communication skills. Future research using objective assessments of underlying social communication skills is required.
PMCID: PMC4275596  PMID: 25451393
Social Anxiety Disorder; Child; Social communication; Autism spectrum; Anxiety
2.  Maternal postnatal depression predicts altered offspring biological stress reactivity in adulthood 
Psychoneuroendocrinology  2015;52:251-260.
•Postnatally depressed (PND) mothers’ offspring showed increased cortisol stress reactivity.•This response at age 22-years was relative to control offspring.•There was also evidence of stable alterations in cortisol secretion in the PND group.•Offspring or subsequent maternal depression did not explain group differences.•Early maternal depression can predict offspring biological sensitivity to stress.
The offspring of depressed parents have been found to show elevated basal levels of the stress hormone cortisol. Whether heightened cortisol stress reactivity is also present in this group has yet to be clearly demonstrated. We tested whether postnatal maternal depression predicts subsequent increases in offspring biological sensitivity to social stress, as indexed by elevated cortisol reactivity.
Participants (mean age 22.4-years) derived from a 22-year prospective longitudinal study of the offspring of mothers who had postnatal depression (PND group; n = 38) and a control group (n = 38). Salivary cortisol response to a social-evaluative threat (Trier Social Stress Test) was measured.
Hierarchical linear modelling indicated that PND group offspring showed greater cortisol reactivity to the stress test than control group participants. Group differences were not explained by offspring depressive or anxiety symptoms, experiences of negative life events, elevated basal cortisol at age 13-years, subsequent exposure to maternal depression, or other key covariates.
The findings indicate that the presence of early maternal depression can predict offspring biological sensitivity to social stress in adulthood, with potential implications for broader functioning.
PMCID: PMC4309884  PMID: 25544737
Depression; Stress sensitivity; Cortisol; Maternal depression; Longitudinal; Hypothalamic–pituitary–adrenal axis
3.  The polysaccharide inulin is characterized by an extensive series of periodic isoforms with varying biological actions 
Glycobiology  2013;23(10):1164-1174.
In studying the molecular basis for the potent immune activity of previously described gamma and delta inulin particles and to assist in production of inulin adjuvants under Good Manufacturing Practice, we identified five new inulin isoforms, bringing the total to seven plus the amorphous form. These isoforms comprise the step-wise inulin developmental series amorphous → alpha-1 (AI-1) → alpha-2 (AI-2) → gamma (GI) → delta (DI) → zeta (ZI) → epsilon (EI) → omega (OI) in which each higher isoform can be made either by precipitating dissolved inulin or by direct conversion from its precursor, both cases using regularly increasing temperatures. At higher temperatures, the shorter inulin polymer chains are released from the particle and so the key difference between isoforms is that each higher isoform comprises longer polymer chains than its precursor. An increasing trend of degree of polymerization is confirmed by end-group analysis using 1H nuclear magnetic resonance spectroscopy. Inulin isoforms were characterized by the critical temperatures of abrupt phase-shifts (solubilizations or precipitations) in water suspensions. Such (aqueous) “melting” or “freezing” points are diagnostic and occur in strikingly periodic steps reflecting quantal increases in noncovalent bonding strength and increments in average polymer lengths. The (dry) melting points as measured by modulated differential scanning calorimetry similarly increase in regular steps. We conclude that the isoforms differ in repeated increments of a precisely repeating structural element. Each isoform has a different spectrum of biological activities and we show the higher inulin isoforms to be more potent alternative complement pathway activators.
PMCID: PMC3766280  PMID: 23853206
adjuvant; carbohydrate; inulin; isoform; vaccine
4.  Emotional reasoning and anxiety sensitivity: Associations with social anxiety disorder in childhood☆ 
Journal of Affective Disorders  2014;152-154(100):219-228.
Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object.
The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7–12 years).
Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios.
This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution.
The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders.
PMCID: PMC3878593  PMID: 24120086
Child; Anxiety; Cognition; Social anxiety disorder; Emotional reasoning; Anxiety sensitivity
5.  An 18-Month Study of the Safety and Efficacy of Repeated Courses of Inhaled Aztreonam Lysine in Cystic Fibrosis 
Pediatric pulmonology  2010;45(11):10.1002/ppul.21301.
Chronic airway infection with Pseudomonas aeruginosa (PA) causes morbidity and mortality in patients with cystic fibrosis (CF). Additional anti-PA therapies are needed to improve health status and health-related quality of life. AIR-CF3 was an international 18-month, open-label study to evaluate the safety and efficacy of repeated courses of aztreonam for inhalation solution (AZLI, now marketed as Cayston®) in patients aged ≥6 years with CF and PA infection who previously participated in one of two Phase 3 studies: AIR-CF1 or AIR-CF2. Patients received up to nine courses (28 days on/28 days off) of 75 mg AZLI two (BID) or three times daily (TID) based on randomization in the previous trials. 274 patients, mean age 28.5 years (range: 8–74 years), participated. Mean treatment adherence was high (92.0% BID group, 88.0% TID group). Hospitalization rates were low and adverse events were consistent with CF With each course of AZLI, FEV1 and scores on the Cystic Fibrosis Questionnaire-Revised Respiratory Symptomscale improved and bacterial density in sputum was reduced. Benefits waned in the 28 days off therapy, but weight gain was sustained over the 18months. There were no sustained decreases in PA susceptibility. A dose response was observed; AZLI TID-treated patients demonstrated greater improvements in lung function and respiratory symptoms over 18 months. Repeated intermittent 28-day courses of AZLI treatment were well tolerated. Clinical benefits in pulmonary function, health-related quality of life, and weight were observed with each course of therapy. AZLI is a safe and effective new therapy in patients with CF and PA airway infection.
PMCID: PMC3867945  PMID: 20672296
antibiotic; Pseudomonas aeruginosa; pulmonary function; quality of life
6.  Congenital orbital teratoma 
Indian Journal of Ophthalmology  2013;61(12):767-769.
We present a case of mature congenital orbital teratoma managed with lid-sparing exenteration and dermis fat graft. This is a case report on the management of congenital orbital teratoma. A full-term baby was born in Fiji with prolapsed right globe which was surrounded by a nonpulsatile, cystic mass. Clinical and imaging features were consistent with congenital orbital teratoma. Due to limited surgical expertise, the patient was transferred to Adelaide, Australia for further management. The patient underwent a lid-sparing exenteration with frozen section control of the apical margin. A dermis fat graft from the groin was placed beneath the lid skin to provide volume. Histopathology revealed mature tissues from each of the three germ cell layers which confirmed the diagnosis of mature teratoma. We describe the successful use of demis fat graft in socket reconstruction following lid-sparing exenteration for congenital orbital teratoma.
PMCID: PMC3917402  PMID: 23619505
Congenital; dermis fat graft; orbital; teratoma
7.  Interpretation and Expectation in Childhood Anxiety Disorders: Age Effects and Social Specificity 
Theory and treatment for childhood anxiety disorders typically implicates children’s negative cognitions, yet little is known about the characteristics of thinking styles of clinically anxious children. In particular, it is unclear whether differences in thinking styles between children with anxiety disorders and non-anxious children vary as a function of child age, whether particular cognitive distortions are associated with childhood anxiety disorders at different child ages, and whether cognitive content is disorder-specific. The current study addressed these questions among 120 7–12 year old children (53% female) who met diagnostic criteria for social anxiety disorder, other anxiety disorder, or who were not currently anxious. Contrary to expectations, threat interpretation was not inflated amongst anxious compared to non-anxious children at any age, although older (10–12 year old) anxious children did differ from non-anxious children on measures of perceived coping. The notion of cognitive-content specificity was not supported across the age-range. The findings challenge current treatment models of childhood anxiety, and suggest that a focus on changing anxious children’s cognitions is not warranted in mid-childhood, and in late childhood cognitive approaches may be better focussed on promoting children’s perceptions of control rather than challenging threat interpretations.
PMCID: PMC3936123  PMID: 24293002
Child; Anxiety; Cognition; Social anxiety disorder
8.  The Parental Overprotection Scale: Associations with child and parental anxiety☆ 
Journal of Affective Disorders  2013;151(2):618-624.
Parental overprotection has commonly been implicated in the development and maintenance of childhood anxiety disorders. Overprotection has been assessed using questionnaire and observational methods interchangeably; however, the extent to which these methods access the same construct has received little attention. Edwards et al. (2008, 2010) developed a promising parent-report measure of overprotection (OP) and reported that, with parents of pre-school children, the measure correlated with observational assessments and predicted changes in child anxiety symptoms. We aimed to validate the use of the OP measure with mothers of children in middle childhood, and examine its association with child and parental anxiety.
Mothers of 90 children (60 clinically anxious, 30 non-anxious) aged 7–12 years completed the measure and engaged in a series of mildly stressful tasks with their child.
The internal reliability of the measure was good and scores correlated significantly with observations of maternal overprotection in a challenging puzzle task. Contrary to expectations, OP was not significantly associated with child anxiety status or symptoms, but was significantly associated with maternal anxiety symptoms.
Participants were predominantly from affluent social groups and of non-minority status. Overprotection is a broad construct, the use of specific sub-dimensions of behavioural constructs may be preferable.
The findings support the use of the OP measure to assess parental overprotection among 7–12 year-old children; however, they suggest that parental responses may be more closely related to the degree of parental rather than child anxiety.
PMCID: PMC3808745  PMID: 23916305
Child anxiety; Parent anxiety; Overprotection; Self-report
9.  Analysis of the hydrolysis of inulin using real time 1H NMR spectroscopy 
Carbohydrate Research  2012;352:117-125.
The hydrolysis of various carbohydrates was investigated under acidic conditions in real time by 1H NMR spectroscopy, with a focus on the polysaccharide inulin. Sucrose was used as a model compound to illustrate the applicability of this technique. The hydrolysis of sucrose was shown to follow pseudo first order kinetics and have an activation energy of 107.0 kJ.mol−1 (s.d. 1.7 kJ.mol−1). Inulin, pullulan and glycogen also all followed pseudo first order kinetics, but had an initiation phase at least partially generated by the protonation of the glycosidic bonds. It was also demonstrated that polysaccharide chain length has an effect on the hydrolysis of inulin. For short chain inulin (DPn 18, s.d. 0.70) the activation energy calculated for the hydrolytic cleavage of glucose was similar to sucrose at 108.5 kJ.mol−1 (std. dev. 0.60). For long chain inulin (DPn 30, s.d. 1.3) the activation energy for the hydrolytic cleavage of glucose was reduced to 80.5 kJ.mol−1 (s.d. 2.3 kJ.mol−1). This anomaly has been attributed to varied conformations for the two different lengths of inulin chain in solution.
PMCID: PMC3324600  PMID: 22464225
Inulin; Polysaccharide hydrolysis; 1H NMR spectroscopy
10.  The Effect of Whole Body Vibration Exposure on Muscle Function in Children With Cystic Fibrosis: A Pilot Efficacy Trial 
To examine the effects of whole body vibration (WBV) exposure on muscle function in children with Cystic Fibrosis (CF). Non-randomised controlled cross-over trial.
The setting was home-based WBV exposure. The participants were children (8 - 15 years) with CF (n = 7). Intervention: participants served as their own controls for the first four weeks (usual care), then underwent four weeks of parentally-supervised home-based WBV exposure followed by four weeks washout (usual care). The WBV exposure consisted of 20 - 30 minutes of intermittent (1 min vibration:1 min rest) exposure on a Galileo platform (20 - 22Hz, 1 mm amplitude) 3 days/week. The primary outcome measures of absolute and relative lower body (leg extension (LE), leg press (LP)), upper body (chess press (CP)) strength and power, and power were measured at baseline, and weeks 4, 8 and 12. Secondary exploratory outcomes were cardiorespiratory fitness, pulmonary function and health-related quality of life.
Six participants completed the training without adverse events. Muscle function changes following WBV exposure were not statistically significant. However, moderate-to-large relative effect sizes (ES) favouring WBV were evident for leg extension strength (ES = 0.66 (-0.50, 1.82)), LP relative strength (ES = 0.92 (-0.27, 2.11)), leg press peak power (ES = 0.78 (-0.50, 2.07)) and CMJ height (ES = 0.60 (-0.56 to 1.76)).
The results from this first controlled trial indicate that WBV may be a potentially effective exercise modality to safely increase leg strength and explosive power in children with CF. Potentially clinically relevant changes support continued investigation of the efficacy, mechanism and feasibility of this intervention in future large-scale studies.
PMCID: PMC3651071  PMID: 23671546
Cystic Fibrosis; Children; Vibration; Muscle function; Muscle power
11.  BLAST: a more efficient report with usability improvements 
Nucleic Acids Research  2013;41(Web Server issue):W29-W33.
The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is
PMCID: PMC3692093  PMID: 23609542
12.  Exploring the paradox: double burden of malnutrition in rural South Africa 
Global Health Action  2013;6:10.3402/gha.v6i0.19785.
PMCID: PMC3556714
13.  Observation of the keto tautomer of D-fructose in D2O using 1H NMR spectroscopy 
Carbohydrate Research  2011;347(1):136-141.
D-Fructose was analysed by NMR spectroscopy and previously unidentified 1H NMR resonances were assigned to the keto and α-pyranose tautomers. The full assignment of shifts for the various fructose tautomers enabled the use of 1H NMR spectroscopy in studies of the mutarotation (5 – 25 °C) and tautomeric composition at equilibrium (5 – 50 °C). The mutarotation of β-pyranose to furanose tautomers in D2O at a concentration of 0.18 M was found to have an activation energy of 62.6 kJ.mol−1. At tautomeric equilibrium (20 °C in D2O) the distribution of the β-pyranose, β-furanose, α-furanose, α-pyranose and the keto tautomers was found to be 68.23%, 22.35%, 6.24%, 2.67% and 0.50%, respectively. This tautomeric composition was not significantly affected by varying concentration between 0.089 and 0.36 M or acidification to pH 3. Upon equilibrating at 6 temperatures between 5 and 50 °C there was a linear relationship between the change in concentration and temperature for all forms.
PMCID: PMC3254704  PMID: 22129837
D-Fructose; Carbohydrate structural analysis; Mutarotation; Tautomeric equilibrium
15.  Bacterial Bloodstream Infections in Neonates in a Developing Country 
ISRN Pediatrics  2012;2012:508512.
Background. Ongoing surveillance of antimicrobial sensitivity patterns of bacteria isolated in bloodstream infections guides empiric antibiotic therapy in neonatal sepsis. Methods. Sensitivity profiles of neonatal bacterial bloodstream infections in a tertiary hospital were reviewed between 01/06/2009 and 30/06/2010 . Results. There were 246 episodes of bloodstream infection in 181 individuals—(14.06 episodes in10.35 patients/1000 patient days or 14.4 episodes in 10.6 babies/1000 live births. The majority were (93.5%) were late onset and most (54.9%) were gram positive. There were 2.28 sepsis-related deaths /1000 patient days or 2.3/1000 live births. Death was significantly associated with gram-negative infections (P < 0.001), multiple gestation (P < 0.001), shock (P = 0.008), NEC (P = 0.002), and shorter duration of hospital stay (P < 0.001). Coagulase-negative staphylococcus was isolated in 19.1%, K. pneumoniae ESBL in 12.1%, and A. baumanni in 10.9%. S. agalactiae predominated in early onset sepsis. Methicillin resistance was present in 86% of CoNS and 69.5% of S. aureus; 46% enterococcal isolates were ampicillin resistant. The majority (65%) of K. pneumoniae isolates were ESBL producers. Ampicillin resistance was present in 96% of E. coli. Conclusions. Penicillin and an aminoglycoside would be suitable empiric therapy for early onset sepsis and meropenem with gentamycin or ceftazidime with amikacin for late onset sepsis.
PMCID: PMC3420109  PMID: 22919509
16.  Delta inulin: a novel, immunologically active, stable packing structure comprising β-d-[2 → 1] poly(fructo-furanosyl) α-d-glucose polymers 
Glycobiology  2010;21(5):595-606.
We report a novel isoform of β-d-[2 → 1] poly(fructo-furanosyl) α-d-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37–48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.
PMCID: PMC3106373  PMID: 21147758
adjuvant; carbohydrate; inulin; isoform; vaccine
17.  Carbohydrate-based immune adjuvants 
Expert review of vaccines  2011;10(4):523-537.
The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage.
PMCID: PMC3118391  PMID: 21506649
adjuvants; carbohydrate; glucan; glycomics; immunity; inulin; vaccines
18.  Developmental outcome of very low birth weight infants in a developing country 
BMC Pediatrics  2012;12:11.
Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa.
The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome.
178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69 - 91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85 - 90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0 - 93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome.
Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age.
PMCID: PMC3293066  PMID: 22296705
19.  Education resources of the National Center for Biotechnology Information 
Briefings in Bioinformatics  2010;11(6):563-569.
The National Center for Biotechnology Information (NCBI) hosts 39 literature and molecular biology databases containing almost half a billion records. As the complexity of these data and associated resources and tools continues to expand, so does the need for educational resources to help investigators, clinicians, information specialists and the general public make use of the wealth of public data available at the NCBI. This review describes the educational resources available at NCBI via the NCBI Education page ( These resources include materials designed for new users, such as About NCBI and the NCBI Guide, as well as documentation, Frequently Asked Questions (FAQs) and writings on the NCBI Bookshelf such as the NCBI Help Manual and the NCBI Handbook. NCBI also provides teaching materials such as tutorials, problem sets and educational tools such as the Amino Acid Explorer, PSSM Viewer and Ebot. NCBI also offers training programs including the Discovery Workshops, webinars and tutorials at conferences. To help users keep up-to-date, NCBI produces the online NCBI News and offers RSS feeds and mailing lists, along with a presence on Facebook, Twitter and YouTube.
PMCID: PMC2984538  PMID: 20570844
Bioinformatics; education; tutorials; NCBI; databases; GenBank
20.  An inactivated Vero cell-grown Japanese encephalitis vaccine formulated with Advax, a novel inulin-based adjuvant, induces protective neutralizing antibody against homologous and heterologous flaviviruses 
The Journal of General Virology  2010;91(Pt 6):1407-1417.
Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a traditional non-adjuvanted JEV vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted vaccine (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the unadjuvanted vaccine, were protected against live JEV challenge. Equine immunizations against JEV with Advax-formulated vaccine similarly showed enhanced vaccine immunogenicity, confirming that the adjuvant effects of Advax are not restricted to rodent models. Advax-adjuvanted JEV vaccine elicited a balanced T-helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV vaccine was well tolerated with minimal reactogenicity and no systemic toxicity in immunized animals. The cessation of manufacture of traditional mouse brain-derived unadjuvanted JEV vaccine in Japan has resulted in a JEV vaccine shortage internationally. There is also an ongoing lack of human vaccines against other JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture-grown JEV vaccine a promising candidate to address both needs with one vaccine.
PMCID: PMC2888167  PMID: 20130134
21.  Growth of a cohort of very low birth weight infants in Johannesburg, South Africa 
BMC Pediatrics  2011;11:50.
Little is known about the growth of VLBW infants in South Africa. The aim of this study was to assess the growth of a cohort of VLBW infants in Johannesburg.
A secondary analysis of a prospective cohort was conducted on 139 VLBW infants (birth weight ≤1500 g) admitted to Charlotte Maxeke Johannesburg Academic Hospital. Growth measurements were obtained from patient files and compared with the World Health Organization Child Growth Standards (WHO-CGS) and with a previous cohort of South African VLBW infants. The sample size per analysis ranged from 11 to 81 infants.
Comparison with the WHO-CGS showed initial poor growth followed by gradual catch up growth with mean Z scores of 0.0 at 20 months postmenstrual age for weight, -0.8 at 20 months postmenstrual age for length and 0.0 at 3 months postmenstrual age for head circumference. Growth was comparable with that of a previous cohort of South African VLBW infants in all parameters.
Initial poor growth in the study sample was followed by gradual catch up growth but with persistent deficits in length for age at 20 months postmenstrual age relative to healthy term infants.
PMCID: PMC3115871  PMID: 21619702
22.  Feasibility of guided cognitive behaviour therapy (CBT) self‐help for childhood anxiety disorders in primary care 
Anxiety disorders in childhood are common, disabling and run a chronic course. Cognitive behaviour therapy (CBT) is effective but expensive and trained therapists are scarce. Guided self‐help treatments may be a means of widening access to treatment. This study aimed to examine the feasibility of guided CBT self‐help in primary care for childhood anxiety disorders, specifically in terms of therapist adherence, patient and therapist satisfaction and clinical gain.
Participants were children aged between five and 12 years referred to two primary child and adolescent mental health services (PCAMHSs) in Oxfordshire, UK, who met diagnostic criteria for a primary anxiety disorder. Of the 52 eligible children, 41 anxious children were assessed for anxiety severity and interference before and after receiving CBT self‐help delivered via a parent (total therapy time = five hours) by primary mental health workers (PMHWs). Therapy sessions were rated for treatment adherence and parents and PMHWs completed satisfaction questionnaires after treatment completion. Over 80% of therapy sessions were rated at a high level of treatment adherence. Parents and PMHWs reported high satisfaction with the treatment. Sixty‐one percent of the children assessed no longer met the criteria for their primary anxiety disorder diagnosis following treatment, and 76% were rated as ‘much’/‘very much’ improved on the Clinical Global Impression–Improvement (CGI–I) scale. There were significant reductions on parent and child report measures of anxiety symptoms, interference and depression. Preliminary exploration indicated that parental anxiety was associated with child treatment outcome. The findings suggest that guided CBT self‐help represents a promising treatment for childhood anxiety in primary care.
PMCID: PMC2925164  PMID: 22477922
child anxiety; cognitive behaviour therapy (CBT); primary care
23.  Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg 
BMC Pediatrics  2010;10:30.
Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting.
This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival.
Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31).
Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.
PMCID: PMC2885379  PMID: 20444296
24.  Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trial 
Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances.
Design Randomised controlled trial.
Setting Khayelitsha, a peri-urban settlement in South Africa.
Participants 449 pregnant women.
Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team.
Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months.
Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=−2.04 , P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=−1.76 (0.86), t=2.28 , P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale).
Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world.
Trial registration Current Controlled Trials ISRCTN25664149.
PMCID: PMC2669116  PMID: 19366752
25.  Postnatal depression  
BMJ : British Medical Journal  1998;316(7148):1884-1886.
PMCID: PMC1113362  PMID: 9632411

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