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Occipitofrontal circumference (OFC) is one of the few physical findings in autism that varies significantly from the norm and is distinct and measurable. As part of a study of genetic heterogeneity of autism, we scrutinized data from a large sample of patients with idiopathic autism (N = 137), using OFC as the categorizing variable. The OFC standard deviation (OFCSD) values of the autistic propositi (0.61+/-1.6) varied significantly from that of the normal population (0.0+/-1.0), (P0.001). Comparison of the macrocephalic (OFCSD2.0, N = 32) with the normocephalic individuals (-2 SDOFCSD+2 SD, N = 95) showed no significant differences in sex ratio, morphological status, IQ, seizure prevalence, or recurrence risks. The macrocephalic individuals were slightly less apt than those with normocephaly to have a family history of Attention Deficit Hyperactivity Disorder (ADHD) (P0.05). Each clinical subgroup of autism propositi, defined on the basis of phenotypic status, type of onset, seizure history, or IQ, had a higher than normal mean OFC indicating that macrocephaly is an independent clinical trait in autism. As in the non-autistic population, macrocephaly was highly familial with 45% of the macrocephalic and 37% of the normocephalic propositi having at least one macrocephalic parent. Microcephaly, however, was an independent significant variable that predicted the presence of other phenotypic or genetic traits and outcome. The microcephalic patients were more likely to have abnormal physical morphology, structural brain malformations, lower IQ, and seizures. Their sex ratio was closer to normal, and their relatives had a higher incidence of seizures.

In an effort to delineate more homogeneous autism subgroups for genetic study, we evaluated 133 consecutive individuals referred to the University of Missouri Autism Center. Each index case underwent a diagnostic evaluation, including a clinical morphology examination, laboratory studies, brain MRI, EEG, and collection of historical, medical, and family data. The 71% (94/133) who fulfilled DSM-IV and CARS autism diagnostic criteria were included in this study. Six of 94 were diagnosed with a known genetic disorder. Of the remaining 88 with apparently "idiopathic autism," 58% (51/88) were phenotypically normal, 22% (19/88) were clearly abnormal, and for 20% (18/88) the clinical morphology examination was equivocal. The percentage of phenotypically abnormal individuals is higher than generally thought and disagrees with the perception that children with autism are usually normally formed. The phenotypically abnormal individuals were 10 times more likely to be diagnosed with a known genetic syndrome (21% vs. 2%) and were more than twice as likely (29% vs. 14%) to have structurally abnormal brain MRIs than the phenotypically normal propositi. Moreover, the male to female ratio correlated with the presence of physical anomalies. The total study group had a male to female ratio of 4.2:1; the morphologically normal subgroup, defined on the basis of a normal physical examination, had a sex ratio of 7.5:1 and the normal subgroup, defined on the basis of both a normal physical examination and a structurally normal brain by MRI had a 23:1 sex ratio. For the phenotypically abnormal subgroup, the sex ratio was 1.7:1. Since differences in sex ratio are presumably a reflection of differences in genetic constitution, we postulate that the phenotypically normal subgroup of individuals with "idiopathic autism" is genetically different from the phenotypically abnormal individuals and that differences in the sex ratio in different autism populations is one indicator of a population's genetic heterogeneity.

Arytenoid adduction was designed to enhance posterior glottal closure in patients with paralytic dysphonia by reproducing lateral cricoarytenoid muscle function. However this procedure can exaggerate normal medial rotation of the vocal process, because the agonist-antagonist function of the interarytenoid, lateral thyroarytenoid, and posterior cricoarytenoid muscles is not simulated. Therefore, a new adduction procedure (adduction arytenopexy) was devised to affix the arytenoid on the cricoid facet in a more optimal position for glottal sound production. The adduction arytenopexy procedure was designed on fresh cadavers. In this technique, the lateral aspect of the cricoarytenoid joint is opened widely and the body of the arytenoid is manually medialized along the cricoid facet. A specially designed single suture is then placed through the posterior cricoid and the body or the muscular process of the arytenoid to achieve 2-point fixation. This draws the arytenoid posteriorly, superiorly, and medially for precise positioning. The arytenoid is rocked internally on the cricoid facet, and suture tension is adjusted appropriately to simulate normal cricoarytenoid adduction. In the first study, the adduction arytenopexy was compared with the classic arytenoid adduction in 10 fresh cadaver larynges. The new arytenopexy procedure resulted in an average increase of 2.1 mm (p.01) in the length of the musculomembranous vocal fold, whereas the classic arytenoid adduction did not reveal a significant change in length. Additionally, the adduction arytenopexy resulted in a consistently higher vocal fold and a more normally contoured arytenoid than the classic adduction procedure. The second study consisted of a clinical trial in which 12 patients, who presented with a widely patent posterior glottis, underwent adduction arytenopexy in conjunction with implant medialization. The procedure was successful in all patients, and there were minimal complications. In the third study, preoperative and postoperative vocal assessment measures (stroboscopic, aerodynamic, acoustic, and perceptual) were analyzed in 9 of the 12 patients. The most striking preoperative stroboscopic observation was that 8 of the 9 patients presented with an aperiodic vibrational flutter during phonation due to severe valvular incompetence. Postoperatively, all patients developed complete closure of the glottal chink and effective entrained oscillation of the vocal folds. This visual improvement in function was commensurate with comparable changes in most of the other objective and subjective measures of vocal function. The new adduction arytenopexy procedure closely simulates the biomechanics underlying normal glottal closure and cricoarytenoid adduction. In turn, complex implant design shapes are not necessary to achieve proper alignment of the arytenoid and the vocal fold. Because the arytenoid is properly positioned prior to the medialization, implants can be sized more precisely and are unencumbered by an anterior thyroid lamina suture. These procedural innovations resulted in enhanced entrained oscillation of the glottal valve and, in turn, improved laryngeal sound production.

This two-part investigation assessed functional outcomes related to communication (including amount of speech therapy), swallowing and eating, and employment status for patients who received one of the two treatment modalities for advanced laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans Administration Cooperative Study #268. One hundred sixty-six patients were randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to induction chemotherapy (CT) and RT. The first investigation dealt with examining and comparing functional outcomes for patients in the two treatment arms of the main study. Results showed clearly that patients with advanced laryngeal cancer are better off from the standpoint of speech communication if they can be treated for this disease without removal of the larynx. In contrast, there were few significant differences between patient groups for other non-speech-related measures. The second investigation focused on communication-related outcomes associated with the rehabilitation of total laryngectomy patients. Results revealed that only relatively small percentages of total laryngectomy patients (6%) developed usable esophageal speech or remained nonvocal (8%), and that a majority of patients ended up as users of artificial electrolarynx (55%) or tracheoesophageal (31%) speech. The results from both investigations are discussed with respect to factors that can influence the rehabilitation process and long-term outcome status of patients who are treated for advanced laryngeal cancer with these two strategies.

We unknowingly "screened" all NICU infants for elevated levels of serum benzyl alcohol (Bz-OH) over a three-month period. The fortuitous "screening" procedure resulted from the interference by Bz-OH with a routine blood CO2 assay used for all infants; validity was proved by (1) replication of the interference pattern with Bz-OH or benzoic acid; (2) confirmation of elevated benzoic acid levels in serum in two of the four screening positive infants tested but not in control infants, and (3) disappearance of the interference patterns when Bz-OH solutions were discontinued in affected infants. Screened Bz-OH-positive infants were compared to screened negative control infants, matched for weight (less than 1000 g), severity of RDS (on respirators), exposure to Bz-OH, and survival for longer than 48 hours. Intraventricular hemorrhage (IVH), metabolic acidosis appearing prior to IVH, and mortality were increased in Bz-OH-positive infants (P less than .05 in each case); hyperbilirubinemia and thrombocytopenia were not. Gasping respirations were not a major symptom. It is concluded that Bz-OH poisoning was a major cause of morbidity and mortality in NICU infants weighing less than 1000 g at birth during the three-month screening period. A retrospective review of patient records covering a 16-month period showed significant improvement in the survival rate of infants weighing less than 1000 g following the discontinuation of Bz-OH solutions.

We describe a micromethod for measuring hexachlorophene by use of gas-liquid chromatography with a 63Ni electron capture detector. The procedure requires 100 micronl of blood for extractions of hexachlorophene, and dichlorophene is added as an internal standard. CV is 3.4% over the concentration range of 500 to 1300 microng of hexachlorophene per liter of whole blood. This procedure permits repeated measurements of hexachlorophene in newborns who are being washed with soap containing hexachlorophene.

We analyzed extensively a modified thiochrome method for thiamin analysis. Acid phosphatase (EC 3.1.3.2) from potato was superior to either alpha-amylase or acid phosphatase from wheat germ as a dephosphorylating agent. Timing of cyanogen bromide exposure was important, but the assay had good precision and accuracy. The standard curve was linear from 10 to 3000 nmol/L. The within-run and between-run coefficients of variation for total thiamin in whole blood were 3.6% and 7.4%, respectively. Analytical recoveries for low, intermediate, and high additions of thiamin to whole blood were 93-109%. Sample yield was increased by 41% (+/- 29% SD) with pre-assay freezing. Samples were stable for two days at room temperature, for seven days when refrigerated, and for two years when frozen. Previously unreported interference was seen with penicillin derivatives, and with several commonly used diuretic and antiepileptic medications. This assay may be suitable for population screening; 200 samples could be analyzed weekly at a cost of +0.20 per sample.

At last year’s Symposium ‘Designing from the inside out’ the keynote address made a strong case for improved matching of the machine to the man, starting with an understanding at the project stage of the optimum way that systems should be designed to achieve integration between man and machine. This year, we are discussing one aspect of human engineering—the presentation of information to the pilot.

The greatly increased cost of fuel has intensified the need for the manufacturer to increase operating efficiency in the aerodynamic, structural and propulsion fields. These aspects have already been highly refined and further improvements will be more and more difficult to realise. However, DOC is also equally affected by equipment and crew costs and this paper therefore attempts to examine the potential for improvements to the flight deck that will determine the most cost-effective combination of crew and equipment required for the safe operation of relatively large transport aircraft.In the past, design effort has, very logically, been concentrated on those fields that could be shown to give an obvious economic return, and since investment in new instrumentation, flight deck workload analysis and system automation showed less tangible results than increases in speed, range, payload, etc, there was no great incentive to allocate money and effort to “human engineering”.

Twenty years ago, the electronic valve gave way to the transistor; now the transistor as a discrete component has been replaced by the integrated circuit, and micro-processors are emerging as cheap, reliable and basic elements of electronic architecture.Each step has yielded a major reduction in the size of equipment needed to achieve a particular function or to improve performance—but in spite of miniaturisation, an increasing volume of avionics has been incorporated into succeeding generations of aircraft as requirements for greater precision and safety have arisen.Application has already provided striking improvements in the quality and ease of communication and navigation, which in turn have brought about the demise of the dedicated radio operator and navigator. The trend will continue with more automation of flight control and system management, leading to two-crew operation of most short and medium range aircraft—providing, of course, that the cost of ownership of additional equipment is less than the costs of the displaced crew member, and that flight safety standards continue to improve.

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.

A semimicro method for measuring propionic and other short-chain fatty acids in serum is presented. The procedure requires as little as 200 microliter of serum. Data are provided for premature infants, children, adults, and patients with propionicacidemia.

We have investigated the Kodak Ektachem 400 Analyzer procedure for CO2 for interferences from benzyl alcohol, benzoic acid, and several compounds structurally similar to benzoic acid. Benzoic acid in plasma, at concentrations found in neonates intoxicated with benzyl alcohol, caused a large increase in the results for CO2, as did substantially above-normal concentrations of certain fatty acids and keto-acids, and toxic concentrations of aspirin. We observed a correlation between increasing benzoic acid concentrations (up to 17 mmol/L) and falsely increasing CO2 values (greater than 47 mmol/L) obtained with the Ektachem Analyzer for samples from a neonate in the intensive-care unit, who was receiving benzyl alcohol-preserved saline solutions. Although the Ektachem CO2 procedure is simple and rapid, and in most cases accurate, questionable results are occasionally encountered, as indicated by a low anion gap or a measured CO2 exceeding that calculated from blood gas measurements. Such results require the use of another method for verification.

We analyzed extensively a modified thiochrome method for thiamin analysis. Acid phosphatase (EC 3.1.3.2) from potato was superior to either alpha-amylase or acid phosphatase from wheat germ as a dephosphorylating agent. Timing of cyanogen bromide exposure was important, but the assay had good precision and accuracy. The standard curve was linear from 10 to 3000 nmol/L. The within-run and between-run coefficients of variation for total thiamin in whole blood were 3.6% and 7.4%, respectively. Analytical recoveries for low, intermediate, and high additions of thiamin to whole blood were 93-109%. Sample yield was increased by 41% (+/- 29% SD) with pre-assay freezing. Samples were stable for two days at room temperature, for seven days when refrigerated, and for two years when frozen. Previously unreported interference was seen with penicillin derivatives, and with several commonly used diuretic and antiepileptic medications. This assay may be suitable for population screening; 200 samples could be analyzed weekly at a cost of +0.20 per sample.

A semimicro method for measuring propionic and other short-chain fatty acids in serum is presented. The procedure requires as little as 200 microliter of serum. Data are provided for premature infants, children, adults, and patients with propionicacidemia.

We describe a micromethod for measuring hexachlorophene by use of gas-liquid chromatography with a 63Ni electron capture detector. The procedure requires 100 micronl of blood for extractions of hexachlorophene, and dichlorophene is added as an internal standard. CV is 3.4% over the concentration range of 500 to 1300 microng of hexachlorophene per liter of whole blood. This procedure permits repeated measurements of hexachlorophene in newborns who are being washed with soap containing hexachlorophene.

We unknowingly "screened" all NICU infants for elevated levels of serum benzyl alcohol (Bz-OH) over a three-month period. The fortuitous "screening" procedure resulted from the interference by Bz-OH with a routine blood CO2 assay used for all infants; validity was proved by (1) replication of the interference pattern with Bz-OH or benzoic acid; (2) confirmation of elevated benzoic acid levels in serum in two of the four screening positive infants tested but not in control infants, and (3) disappearance of the interference patterns when Bz-OH solutions were discontinued in affected infants. Screened Bz-OH-positive infants were compared to screened negative control infants, matched for weight (less than 1000 g), severity of RDS (on respirators), exposure to Bz-OH, and survival for longer than 48 hours. Intraventricular hemorrhage (IVH), metabolic acidosis appearing prior to IVH, and mortality were increased in Bz-OH-positive infants (P less than .05 in each case); hyperbilirubinemia and thrombocytopenia were not. Gasping respirations were not a major symptom. It is concluded that Bz-OH poisoning was a major cause of morbidity and mortality in NICU infants weighing less than 1000 g at birth during the three-month screening period. A retrospective review of patient records covering a 16-month period showed significant improvement in the survival rate of infants weighing less than 1000 g following the discontinuation of Bz-OH solutions.

Increased Parathyroid hormone serum concentrations, [PTH] enhance 1,25-(OH)2D and decrease 24,25-(OH)2D synthesis from 25-hydroxy vitamin D (25-OHD). At term, pregnant women have elevated PTH and infants have low [PTH]. 16 pairs of maternal (M) and umbilical cord (C) venous sera were analyzed for 24,25-(OH)2D, 25-OHD, calcium, magnesium and PTH. Both M 24,25-(OH)2D (2.6±0.5 ng/ml) and C 24,25-(OH)2D (3.0±1.2 ng/ml) were lower than 29 adult normals (5.0±0.6 ng/ml). Normal adult 24,25-(OH)2D is correlated with 25-OHD (R=.40 P