Baseline incidence of adverse birth outcomes and infant influenza and pertussis hospitalisations prior to the introduction of influenza and pertussis vaccination in pregnancy: a data linkage study of 78 382 mother-infant pairs, Northern Territory, Australia, 1994-2015.

We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994-2014) formed the cohort of 78 382 births. Aboriginal mother-infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000-2015) and Immunisation Register datasets (1994-2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.

Pertussis epidemiology prior to the introduction of a maternal vaccination program, Queensland Australia.

Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.

Genital herpes: an Internet-based risk survey.

Genital herpes is one of the most common sexually transmitted infections worldwide. We established a web-based survey to determine risk for genital herpes and encourage people to attend for herpes simplex virus testing. A survey was established on the Australian Herpes Management Forum (AHMF) website, consisting of 16 demographic and sexual health-related questions. Each question carried a numerical risk-weighting based on epidemiological data; the higher the overall score, the greater the risk of herpes. To determine how representative our sample was in relation to age and sex, we compared our survey with Australian Census data. Between October 2006 and August 2007 there were 5572 responses, 4358 (92%) were Australian. Compared with the Australian population, the survey population had a higher proportion of individuals aged less than 34 years, and a lower population over 55. Six hundred and eighty-six (13.8%) were classified as low risk, 2558 (51.6%) as medium risk and 1710 (34.5%) as high risk of having acquired genital herpes. In total, 39% reported four or fewer, and 38% reported 10 or more, sex partners in their lifetime. A large number of individuals participated in this survey, confirming that the Internet is a useful tool for health promotion for genital herpes.

Modification of the restoration protocol for resin-based composite (RBC) restoratives (conventional and bulk fill) on cuspal movement and microleakage score in molar teeth.

OBJECTIVE: To modify the resin-based composite (RBC) restoration protocol for standardised Class II cavities in third molar teeth restored using conventional RBCs or their bulk fill restorative counterparts. Employing cuspal deflection using a twin channel deflection measuring gauge (during) and microleakage to determine marginal integrity (following) RBC restoration, the modified restoration protocol results were compared with traditional (oblique) restoration of Class II cavities. METHODS: Thirty-two sound third molar teeth, standardised by size and morphology, were subjected to standardised Class II cavity preparations and randomly allocated to four groups. Restorations were placed in conjunction with a universal bonding system and resin restorative materials were irradiated with a light-emitting-diode light-curing-unit. The cumulative buccal and palatal cuspal movements from a twin channel deflection measuring gauge were summed, the restored teeth fatigued thermally prior to immersion in 0.2% basic fuchsin dye for 24h, before sectioning and examination for microleakage. RESULTS: Teeth restored using conventional RBC materials had significantly higher mean total cuspal movement values compared with bulk fill resin restorative restoration (all p<0.0001). Teeth restored with Admira Fusion and Admira Fusion x-tra had significantly the lowest microleakage scores (all p<0.001) compared with Tetric EvoCeram and Tetric EvoCeram Bulk Fill restored teeth. The microleakage scores for the range of RBC materials tested were significantly reduced (all p<0.001) when the modified RBC restoration protocol was employed compared with the traditional Class II restoration technique. SIGNIFICANCE: Modification of the RBC restoration protocol of some conventional RBCs and bulk fill resin restoratives significantly improve bond integrity and could be translated as a validation of the limited clinical studies available on bulk fill materials in the dental literature where Class II cavities perform less well than Class I cavities following extended follow-up. CLINICAL SIGNIFICANCE: The results of the current study add further weight to experimental protocols employing cuspal movement (during) and cervical microleakage (following) RBC restoration of standardised cavities in natural dentition to provide an indication of polymerization shrinkage stress at the tooth/RBC restoration interface in a 'clinically meaningful context'.

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo.

PURPOSE: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. MATERIALS AND METHODS: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. RESULTS: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). CONCLUSIONS: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.

A Four-Biomarker Blood Signature Discriminates Systemic Inflammation Due to Viral Infection Versus Other Etiologies.

The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established. Based on 44 publicly available datasets and two clinical studies of our own design, we discovered and validated a four-gene expression signature in whole blood, indicative of a general host systemic response to many types of viral infection. The signature's genes are: Interferon Stimulated Gene 15 (ISG15), Interleukin 16 (IL16), 2',5'-Oligoadenylate Synthetase Like (OASL), and Adhesion G Protein Coupled Receptor E5 (ADGRE5). In each of 13 validation datasets encompassing human, macaque, chimpanzee, pig, mouse, rat and all seven Baltimore virus classification groups, the signature provides statistically significant (p < 0.05) discrimination between viral and non-viral conditions. The signature may have clinical utility for differentiating host systemic inflammation (SI) due to viral versus bacterial or non-infectious causes.

Characterizing adult attention-deficit/hyperactivity-disorder and comorbid borderline personality disorder: ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors.

OBJECTIVE: To characterize adults with comorbid attention-deficit/hyperactivity-disorder (ADHD) and borderline personality disorder (BPD) with regard to ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors. METHOD: A between-group design compared a group of individuals diagnosed with ADHD (n=40) with a group diagnosed with BPD and who also met the criteria for ADHD (ADHD+BPD) (n=20). RESULTS: Significant differences were observed for both childhood and current impulsivity symptoms, whereby ADHD+BPD exhibited increased impulsivity; no differences on self-report and cognitive measures of impulsivity were reported. The ADHD+BPD group scored significantly higher on measures of depression, anxiety and numerous other axis I and II conditions. The ADHD+BPD group scored significantly lower on most measures of intellectual functioning and attention, however largely not on those relating to response inhibition. Furthermore, group differences were observed for psychosocial factors, including education, substance use and criminal record. CONCLUSION: Comorbid ADHD and BPD is characterized by more symptoms of impulsivity, additional psychopathology, comparatively lower intellectual and attentional functioning and increased psychosocial difficulties.

Long-term study of normal kidneys transplanted into patients with type I diabetes.

We examined the rate of development of the lesions of diabetic nephropathy in transplanted kidneys residing for 6-14 yr in type I (insulin-dependent) diabetic kidney-allograft recipients. Although each recipient had end-stage diabetic nephropathy with his/her own kidneys, there was marked variability in the rate of development of mesangial expansion observed in the transplanted kidneys. The progression of glomerular pathology, including widening of the glomerular basement membrane and expansion of the mesangium, did not correlate significantly with several potential risk factors (e.g., donor source--cadaver or living related, histocompatibility match, age of the recipient or donor, age at onset of diabetes, duration of diabetes before renal failure, immunosuppressive drug dose, blood pressure, and severity of lesions of chronic rejection). However, there was a direct albeit imprecise relationship between the index of mesangial expansion at the final biopsy and the index of glycemic control (r = .61, P less than .01). These observations suggest that currently unknown factor(s) may modulate the progression of diabetic renal disease, even in a population that had uniformly demonstrated nephropathy risk. Our data support the hypothesis that in addition to glycemic control per se, there are risk factors intrinsic to the kidney itself.

Polyacrylamide-streptavidin: a novel reagent for simplified construction of soluble multivalent macromolecular conjugates.

We have developed a soluble macromolecular conjugation reagent, polyacrylamide-streptavidin (PASA), for the simplified preparation of multivalent protein-protein conjugates. Soluble linear polyacrylamide, with a molecular weight of approximately 10(6), has carboxyl groups generated by limited alkaline hydrolysis. It is then activated with carbodiimide, separated from excess carbodiimide, and conjugated to streptavidin. The resulting conjugate, which has approximately 20 streptavidin residues per molecule, can bind biotinylated proteins to produce homo- or heteroconjugates of known composition. We have used this technique to prepare soluble multivalent heteroligating antibody conjugates that can bind either of two antigenically distinct cell lines, as well as reagents that specifically label murine tumor cells with different MHC class I antigens. The method is potentially useful for making multivalent arrays of epitopes for measuring low affinity interactions such as that between the T cell receptor and MHC molecules, as well as for making immunotoxins, tumor labelling conjugates, and complex immunogens.

Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin.

Mouse spleen cells could be preparatively separated into immunoglobulin positive (Ig+) and immunoglobulin-netative (Ig-)populations by incubating as many as 2 X 10(8) cells per 100 mm diameter petri plate coated with specifically purified goat anti-mouse immunoglobulin. The non-adherent population was 95% or more Ig-, and possessed graft versus host and cytotoxic effector activities, as would be expected for T cells. They could also give a mixed lymphocyte reaction and generate cytotoxic effector activity on culture in vitro. The adherent cells could not be released undamaged from plates coated with undiluted anti-Ig, but they could be released from plates coated with a 1/4 or 1/10 dilution of anti-Ig in an irrelevant antibody. The released cells were over 90% viable by trypan-blue staining, and 94% or more of the viable cells were Ig+.

The prevalence and clinical significance of nocturnal hypertension in pregnancy.

OBJECTIVE: To determine (a) the prevalence of hypertension during sleep in pre-eclampsia and gestational hypertension, and (b) whether women with hypertension during sleep have worse pregnancy outcomes than hypertensive pregnant women with controlled (normal) blood pressure (BP) during sleep. DESIGN: Prospective double-blind cohort study. SETTING: Inpatients and outpatients managed in a day assessment unit (DAU) at St George Hospital, Sydney, Australia. PARTICIPANTS: A total of 186 hypertensive pregnant women, 158 of whom had successful 24 h BP monitoring; 40% had proteinuric pre-eclampsia (PE), 43% gestational hypertension (GH) and 17% essential hypertension (EH). INTERVENTIONS: Blood pressure, 24 h non-invasive, monitoring (Spacelabs 90207) was undertaken successfully in 158 women with PE, GH or EH, whether or not they were receiving antihypertensives. Women and clinicians were blinded to results of these BP monitors. Sleep hypertension was defined as BP > 117/68 mmHg at 26-30 weeks or > 123/72 mmHg after 30 weeks gestation. MAIN OUTCOME MEASURES: Maternal and fetal outcomes were compared between women with and without sleep hypertension and the prevalence of sleep hypertension was determined. RESULTS: Sleep hypertension was present in 59%, more commonly in PE (79%) than GH/EH (45%), P < 0.0001. Sleep hypertensives also had higher routine sphygmomanometer BPs [137(10)/91(7) mmHg; mean(SD)] than women with normal sleep BP [130(12)/ 87(8) mmHg] P = 0.007, and higher awake ambulatory blood pressure monitoring (ABPM) BPs [137(8)/88(7) versus 127(7)/79(6) mmHg], P < 0.0001. Awake, but not sleep, average heart rate was lower in sleep hypertensives [85(11) versus 91 (10) beats per minute, bpm], P = 0.002. Sleep hypertensives had a significantly greater frequency of renal insufficiency, liver dysfunction, thrombocytopenia and episodes of (awake) severe hypertension (P < 0.05), as well as lower birth weight babies [2715 (808) versus 3224(598) g, P < 0.0001]. CONCLUSIONS: Hypertension during sleep is a common finding in women with hypertensive disorders of pregnancy, particularly pre-eclampsia. These women also have higher awake BPs and a greater frequency of adverse maternal and fetal outcomes. These findings are largely explained by the greater likelihood of pre-eclamptics having sleep hypertension.

Pregnancy after donor nephrectomy.

Potential female donors frequently ask whether unilateral nephrectomy will impair future childbearing capabilities. To address this question, we surveyed 220 women who underwent donor nephrectomy between 1985 and 1992. Of the 144 women who responded, 33 became pregnant after donation for a total of 45 pregnancies. Seventy-five percent of the pregnancies were carried to term without difficulty. Complications incurred during gestation included miscarriage (13.3%), preeclampsia (4.4%), gestational hypertension (4.4%), proteinuria (4.4%), and tubal pregnancy (2.2%). Four of the 45 pregnancies (excluding miscarriages) required preterm hospitalization, resulting in an overall morbidity of 8.8%. There were no pregnancy-related deaths, and no fetal abnormalities were reported. Problems with persistent hypertension, proteinuria, or changes in renal function were not noted. None of the above complications exceeded what has been noted for the general population. Infertility was a problem in 8.3% (3/36) of our respondents, compared with a worldwide incidence of 16.7%. Based on these results, we conclude that donor nephrectomy is not detrimental to the prenatal course or outcome of future pregnancies.

The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.

Employment patterns after successful kidney transplantation.

We studied 822 kidney transplant recipients followed 1-9 years to determine the dynamics of their entering and leaving the work force. Multivariate analysis revealed that not being diabetic and that being employed pretransplant were associated with a higher rate of posttransplant employment. Some recipients in all pretransplant employment categories, including those receiving disability benefits pretransplant, returned to full-time work posttransplant. The most rapid return to work was in those who had been working full-time or attending school pretransplant. After returning to work, a higher percentage of diabetic recipients stopped working; of those who stopped working, 50% received disability benefits. In contrast, nondiabetic recipients who stopped working full-time were more likely to be retired or working part-time; only 22% received disability benefits.

Long-term survival following kidney transplantation in 100 type I diabetic patients.

Between December 1966 and April 1978, 265 uremic patients with type I diabetes received primary renal allografts at the University of Minnesota. One hundred of the diabetic patients were alive with a functioning graft 10 years after transplantation. The actual 10-year patient and primary graft functional survival rates overall were 40% and 32%, respectively. For recipients of HLA-identical sibling (n = 45), mismatched living-related (n = 121), and cadaver donor grafts (n = 99), the actual 10-year patient survival rates were 64%, 33%, and 36%, respectively, and the actual 10-year graft functional survival rates were 62%, 28%, and 22%, respectively. The differences in patient and graft survival rates between HLA-identical graft recipients and recipients of mismatched related and cadaver grafts were significant (P less than 0.001). Of the 100 patients who survived into a second decade, at 15 years posttransplant 51% were alive, and 41% had functioning grafts. For recipients of HLA-identical sibling, mismatched living-related donor grafts, and cadaver donor grafts who survived 10 years, 47%, 57%, and 43%, respectively, were alive at 15 years, and 31%, 45%, and 43%, respectively, had functioning grafts. For recipients who made it to the second decade, patient and primary graft survival rates thereafter were not statistically different by donor source. Twenty-three patients died in the second decade after transplantation, 10 of cardiovascular disease. Twenty-five patients lost graft function in the second decade, 19 from death with a functioning graft. In regard to diabetic complications, recurrence of diabetic nephropathy was common, but only two patients lost graft function solely for this reason. In 21 patients (42 eyes) followed prospectively for 10 years, visual acuity deteriorated in 26%, was stable in 64%, and improved in 10% of eyes. Neurophysiological test results indicated that correction of uremia does not stop the progression of diabetic neuropathy in recipients of kidney transplants alone. Even without cyclosporine, nearly two-thirds of recipients of HLA-identical kidney grafts, more than one-quarter of recipients of mismatched living-related donor grafts, and more than one-fifth receiving cadaver grafts enjoyed an extension of life for more than 10 years.

Evidence for a factor in normal human serum that induces human neutrophilic granulocyte end-stage maturation in vitro.

The end-stage maturation of neutrophilic granulocyte precursor cells isolated from normal human bone marrow by Ficoll density centrifugation was studied in a liquid culture assay system used previously to study the maturation of guinea pig granulocyte precursors. Dialyzed normal human serum induced end-stage morphological maturation of human granulocyte precursors and this induction was proportional to a serum level of up to 5.0% in the assay medium. At serum concentrations greater than 5.0% a pronounced inhibition of maturation was observed. Passage of serum through a DEAE-Fractogel 650S column equilibrated with 0.01 M phosphate buffer (pH 7.0) resulted in the binding of the end-stage granulocyte maturation factor to the column. The activity eluted from the column in a fraction containing 17% of the starting serum protein that was inhibitor-free and was also capable of inducing the appearance of granulocyte alkaline phosphatase, a specific biochemical marker for granulocyte end-stage maturation. GMF is most likely a protein since it was destroyed by protease digestion. The data also indicate that neither purified human transferrin nor human recombinant granulocyte colony-stimulating factor can substitute for human serum GMF as a granulocyte end-stage maturation factor in this assay system. It was observed, however, that purified human transferrin greatly potentiated the effect of GMF suggesting that transferrin plays a supporting role in the end-stage maturation of human granulocytes in vitro. To our knowledge the evidence presented here indicates for the first time the existence of a neutrophilic granulocyte end-stage maturation factor in normal human serum.

Nutrition and growth in pediatric renal transplant recipients.

Pediatric renal failure patients undergo similar rates of growth retardation on all forms of dialysis, but appears to be worst in the patients not dialyzed before transplant and on TF. These patients had an average age of 27 months before transplant. Table 1 shows that all groups undergo progressive decline in growth as the interval from diagnosis to transplant increases. This is not affected by the number of calories supplied. Pretransplant TF seems to improve catch up growth after transplant, but we saw no definite effect on growth in the pretransplant period. Renal transplantation uniformly improves growth in this population.

Repeat cycloplegic examinations at the Naval Operational Medicine Institute.

BACKGROUND: Cycloplegic examination is required for applicants who desire entry into Naval Aviation training. Before this study, all cycloplegic examinations performed at any site were repeated at the Naval Operational Medicine Institute (NOMI), Pensacola, FL, on all student naval aviator (SNA) candidates to assess for latent hyperopia which exceeded established limits for entry into training. HYPOTHESIS: Repeat cycloplegic examination does not vary sufficiently to change student status regarding physical qualification for training. METHODS: Data analysis of cycloplegic examinations repeated at the NOMI, for which the first and second examination were recorded in the Aviation Medical Data Retrieval System (AMDRS), over 10 yr. RESULTS: There were 3919 SNA applicants who had cycloplegic examinations repeated at NOMI. Of them, 3903 (99.59%) were within standards on the repeat examination. There were 16 candidates who were sent to NOMI with a previously disqualifying cycloplegic examination. On second cycloplegic examination, 15 were within standards for SNA. Only 15 of the SNAs with a first cycloplegic examination within standards were outside SNA standards on repeat examination. Of these 15, 12 were also outside SNA standards in distant visual acuity and/or in manifest refraction. The remaining 3 were found to have excessive myopia, not latent hyperopia, on the second cycloplegic examination. The standard deviation between the first and the second cycloplegic examination was computed to be less than 0.50 diopters in any meridian. CONCLUSION: The cycloplegic examination of SNA candidates need only be repeated if the first cycloplegic examination is outside the SNA limit or within two standard deviations of the SNA limit.