The ongoing dissection of the genetic architecture of autistic spectrum disorder

The development of robust, non-hypothesis based case/control studies has led to a large push forward towards identifying common genetic variants that contribute to complex traits. However, despite many attempts, the search for common disease-predisposing variants in childhood developmental disorders has largely failed. Recently, a role for rare causal variants and de novo mutations is emerging in the genetic architecture of some of these disorders, particularly those that incur a large degree of selection against the phenotype. In this paper, we examine these data and use classic genetic epidemiological approaches to gain insights into the genetic architecture of ASD. Future studies using next generation sequencing should elucidate the precise role de novo mutations play in disorders traditionally thought to have resulted from polygenic or common disease, common variants inheritance

Failure to communicate: Inefficiencies in voluntary incentive programs for private forest owners in Michigan

Coordinating forest management across thousands of nonindustrial private forest (NIPF) owners is a difficult yet necessary task for state land management agencies. Voluntary Incentive Programs (VIPs) can coordinate the decentralized activities of these owners in return for services or financial incentives. However, many VIPs typically have low enrollment. Our study investigates the implementation of VIPs to increase forest management coordination among NIPFs in Michigan. We present findings from 20 semi-structured interviews with leaders of state and local land management organizations, and government officials at state natural resource agencies, and contrast their answers with those recorded from 37 interviews of NIPF owners regarding their knowledge and attitudes toward VIPs. Our interviews highlight a critical disconnect between NIPF owner motivations and VIP incentives, as well as misallocated resources for VIP promotion by state agencies, driving low enrollment. At the core, low enrollment in VIPs is generated by inadequate communication between NIPF owners and program managers, along with distrust of government agency objectives. Viewing managers as “street level bureaucrats”, civil servants whose job discretion is impacted heavily by available resources, may increase our understanding of the issues plaguing VIPs and help identify improvements to VIP design and implementation

The Impact of Superior Labral Anterior to Posterior Lesions on Functional Status in Shoulder Instability: A Multicenter Cohort Study

BACKGROUND: Type IV superior labral anterior to posterior (SLAP) lesions, which are superior labral detachments associated with Bankart tears, are reported to occur in up to 25% of recurrent shoulder instability patients. However, the clinical implications of this finding are debatable. PURPOSE: To determine whether there are any functional differences between anterior instability patients with and without type IV SLAP lesions at the time of presentation and at short-term follow-up after surgical intervention. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective, multicenter database was established to follow the clinical evolution of patients with shoulder instability. Patients were diagnosed as having a type IV SLAP lesion at the time of arthroscopic Bankart surgery (SLAP+). These patients were compared with a group of patients who simply had a Bankart lesion (SLAP-). The 2 groups had their functional outcomes (Western Ontario Shoulder Instability Index [WOSI]; Disability of the Arm, Shoulder, and Hand [QuickDASH]; and Walch-Duplay) compared prior to surgery and 1 year postoperatively. RESULTS: A total of 103 subjects were included in the study; of these, 56 (43 men, 13 women) completed 1-year follow-up. Twenty-three subjects had a type IV SLAP tear, and most had this repaired along with their Bankart lesion. At baseline, SLAP+ subjects had inferior QuickDASH scores compared with SLAP- subjects (37.8 vs 29.0) as well as poorer pain subscores on both the WOSI and QuickDASH. At 1-year follow-up, however, there were no significant differences in any of the outcome measures. CONCLUSION: A type IV SLAP lesion can be expected in 22% of patients with recurrent shoulder instability. This finding implies that at baseline, the patient will have slightly worse functional scores related to pain. However, following surgical management of the labral pathology, these patients will have equivalent functional outcomes at short-term follow-up. CLINICAL RELEVANCE: With surgical management of the superior and anteroinferior labrum, patients with type IV SLAP lesions will do as well as those with only Bankart tears. Thus, the presence of SLAP lesions should not alter the decision to provide surgical management and should not change the prognosis for a specific patient

Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

OBJECTIVE: Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects. DESIGN AND METHODS: Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3+/-2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO(2max) to fat-free mass (VO(2max)/FFM), a measure independent of age and fat mass in children. RESULTS: VO(2max)/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO(2max)/FFM (P<0.05), whereas children without hypothalamic involvement had VO(2max)/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia. CONCLUSIONS: Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined

Radioisotopes demonstrate the contrasting bioaccumulation capacities of heavy metals in embryonic stages of cephalopod species

Cephalopods play a key role in many marine trophic food webs and also constitute alternative fishery resources in the context of the ongoing decline in finfish stocks. Most coastal cephalopod species of commercial importance migrate into shallow waters during the breeding season to lay their eggs, and are consequently subjected to coastal contamination. Eggs of common cuttlefish Sepia officinalis, European squid Loligo vulgaris, common octopus Octopus vulgaris and the sepiolid Rossia macrosoma were exposed during embryonic development to dissolved 110mAg, 109Cd, 60Co, 54Mn and 65Zn in order to determine their metal accumulation efficiencies and distribution among different egg compartments. Cuttlefish eggs, in which hard shells enclose the embryos, showed the lowest concentration factor (CF) values despite a longer duration of exposure. In contrast, octopus eggs, which are only protected by the chorionic membrane, accumulated the most metal. Uptake appears to be linked to the selective retention properties of the egg envelopes with respect to each element. The study also demonstrated that the octopus embryo accumulated 110mAg directly from the dissolved phase and also indirectly through assimilation of the contaminated yolk. These results raise questions regarding the potential contrasting vulnerability of early life stages of cephalopods to the metallic contamination of coastal water

Identification of Six Novel SOD1 Gene Mutations in Familial Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SODl) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SODl mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protei

The extinction law in high redshift galaxies

We estimate the dust extinction laws in two intermediate redshift galaxies. The dust in the lens galaxy of LBQS1009-0252, which has an estimated lens redshift of zl~0.88, appears to be similar to that of the SMC with no significant feature at 2175 A. Only if the lens galaxy is at a redshift of zl~0.3, completely inconsistent with the galaxy colors, luminosity or location on the fundamental plane, can the data be fit with a normal Galactic extinction curve. The dust in the zl=0.68 lens galaxy for B0218+357, whose reddened image lies behind a molecular cloud, requires a very flat ultraviolet extinction curve with (formally) R(V)=12 +- 2. Both lens systems seem to have unusual extinction curves by Galactic standards.Comment: 15 pages, 3 figures. ApJ in pres