Estimating Haemophilus influenzae type b vaccine effectiveness in England and Wales by use of the screening method

In October 1992, Haemophilus influenzae type b (Hib) conjugate vaccine was introduced to infants in the United Kingdom with a "catch-up" program for those aged <4 years. Initially, the rate of invasive Hib disease decreased dramatically but has been increasing since 1999. To determine possible reasons for this increase, the effectiveness of Hib conjugate vaccine was estimated by use of the screening method. Between October 1993 and December 2001, a total of 443 cases of Hib infection occurred in children eligible for vaccination; 363 (82%) were fully vaccinated. Vaccine effectiveness was estimated to be 56.7% (95% confidence interval, 42.5-67.4). Effectiveness was lower in children vaccinated during infancy, compared with those who were vaccinated during the catch-up campaign (P=.0033), declined with time since vaccination (P=.0008), and was lower in children born during 2000-2002, compared with other children scheduled for infant vaccination (P=.0041). Use of a catch-up vaccination program enhanced the control of Hib infection in England and Wales. Since 1999, however, low effectiveness in infants, declining effectiveness with age, and the use of lower-efficacy vaccines have contributed to increased rates of Hib infection. The potential role of boosters needs to be considered.     

Normal functional protein S activity does not exclude protein S deficiency

Protein S (PS) deficiency appears to increase the risk of venous thrombosis. PS deficiency is classified into three phenotypes using antigenic levels and functional activity. By definition, all three phenotypes of PS deficiency should result in low activated protein C cofactor activity. We compared the results of functional PS activity testing to free antigenic PS testing in order to determine if a normal functional PS activity assay result could eliminate the need for free antigenic PS testing. The sensitivity of the functional assay is 45.5% (95% confidence interval, CI, 36-55%), specificity 95.3% (95% CI 93-97%), negative predictive value 88.6% (95% CI 86-91%) with a positive predictive value of 68.5% (95% CI 57-79%). In conclusion, a normal functional PS activity result does not exclude free antigenic PS deficiency. Functional PS activity testing should not be used as a screening test to eliminate free antigenic PS testing for the laboratory diagnosis of PS deficiency.     

Left-sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant malformation syndrome characterized by unilaterally distributed ichthyosiform nevi, often sharply delimited at the midline, and ipsilateral limb defects. At least two-thirds of cases demonstrate involvement of the right side. Mutations in an essential enzyme of cholesterol biosynthesis, NAD(P)H steroid dehydrogenase-like [NSDHL], have been reported in five unrelated patients with right-sided CHILD syndrome and in a sixth patient with bilaterally, symmetric nevi and mild skeletal anomalies, but not with CHILD syndrome as originally defined. Although all of the molecularly diagnosed cases with the CHILD phenotype to date have had right-sided disease, we report here a novel nonsense mutation (E151X) of NSDHL in an infant with left-sided CHILD syndrome. This result demonstrates that both right- and left-sided CHILD syndrome can be caused by mutations in the same gene.     

Toward a revised evolutionary adaptationist analysis of depression: the social navigation hypothesis

Evolutionary biologists use Darwinian theory and functional design ("reverse engineering") analyses, to develop and test hypotheses about the adaptive functions of traits. Based upon a consideration of human social life and a functional design analysis of depression's core symptomatology we offer a comprehensive theory of its adaptive significance called the Social Navigation Hypothesis (SNH). The SNH attempts to account for all intensities of depression based on standard evolutionary theories of sociality, communication and psychological pain. The SNH suggests that depression evolved to perform two complimentary social problem-solving functions. First, depression induces cognitive changes that focus and enhance capacities for the accurate analysis and solution of key social problems, suggesting a social rumination function. Second, the costs associated with the anhedonia and psychomotor perturbation of depression can persuade reluctant social partners to provide help or make concessions via two possible mechanisms, namely, honest signaling and passive, unintentional fitness extortion. Thus it may also have a social motivation function.     

CT-derived estimation of cochlear morphology and electrode array position in relation to word recognition in Nucleus-22 recipients

This study extended the findings of Ketten et al. [Ann. Otol. Rhinol. Laryngol. Suppl. 175:1–16 (1998)] by estimating the three-dimensional (3D) cochlear lengths, electrode array intracochlear insertion depths, and characteristic frequency ranges for 13 more Nucleus-22 implant recipients based on in vivo computed tomography (CT) scans. Array insertion depths were correlated with NU-6 word scores (obtained one year after SPEAK strategy use) by these patients and the 13 who used the SPEAK strategy from the Ketten et al. study. For these 26 patients, the range of cochlear lengths was 29.1–37.4 mm. Array insertion depth range was 11.9–25.9 mm, and array insertion depth estimated from the surgeon's report was 1.14 mm longer than CT-based estimates. Given the assumption that the human hearing range is fixed (20–20,000 Hz) regardless of cochlear length, characteristic frequencies at the most apical electrode (estimated with Greenwood's equation [Greenwood DD (1990) A cochlear frequency–position function of several species–29 years later. J Acoust. Soc. Am. 33: 1344–1356] and a patient-specific constant as) ranged from 308 to 3674 Hz. Patients' NU-6 word scores were significantly correlated with insertion depth as a percentage of total cochlear length (R = 0.452; r2 = 0.204; p = 0.020), suggesting that part of the variability in word recognition across implant recipients can be accounted for by the position of the electrode array in the cochlea. However, NU-6 scores ranged from 4% to 81% correct for patients with array insertion depths between 47% and 68% of total cochlear length. Lower scores appeared related to low spiral ganglion cell survival (e.g., lues), aberrant current paths that produced facial nerve stimulation by apical electrodes (i.e., otosclerosis), central auditory processing difficulty, below-average verbal abilities, and early Alzheimer's disease. Higher scores appeared related to patients' high-average to above-average verbal abilities. Because most patients' scores increased with SPEAK use, it is hypothesized that they accommodated to the shift in frequency of incoming sound to a higher pitch percept with the implant than would normally be perceived acoustically.