Search

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a “shift” of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

A century-long daily sea surface salinity (SSS) record from the Scripps Institution of Oceanography (SIO) Pier, La Jolla, CA features short-term (~ 1 week) fresh anomalies (< -0.3 psu) associated with rain events. During the peak wet season (January-March, JFM) the SSS anomaly 10% quantile (SSS10) correlates significantly with nearby river outflow, local and regional measures of precipitation, as well as with a similar SSS10 time series from the Newport Beach Pier (100 km to the north), indicating that the Scripps salinity record provides a measure of year-to-year variations in regional winter precipitation levels and runoff to the coastal ocean. Correlations between SSS10 and El Niño Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO) indices are low; however, negative ENSO (La Niña) and PDO phases correspond consistently with high SSS10/dry winters. In particular, high SSS10 winters tend to cluster during negative decadal phases of the PDO, including a notable three-decade span from 1944–1977 and the current unusually dry period since 2006. Low SSS10/wet winters occur during positive PDO and ENSO phases, although not exclusively, as dry winters are as likely during positive phases. Shifts in Northeast Pacific wind and moisture climatologies, captured in reference to ENSO and PDO phases, help to interpret wet winter variations captured by the salinity record. The long SSS10 time series emphasizes the strong constraint that negative ENSO and PDO phases have on winter drought conditions in southern California, and provides an ocean-based metric for assessing decadal rainfall variations that impact the region.

The American Speech-Language-Hearing Association (ASHA) describes the supervisory process as a collaborative effort between both the student clinician and the certified supervisor. In order to support this process, it is important that both the supervisor and supervisee's preferences be considered regarding how these efforts will proceed. The purpose of this study was to investigate the opinions of graduate speech-language pathology clinicians regarding the supervision provided by on-campus clinical educators. Eighty-four graduate students completed an online survey. Results indicated that students generally preferred supervisory practices that simultaneously promote clinical independence while offering knowledge and support in a structured and timely manner.

Harmful algal bloom (HAB) events threaten human health, living marine resources, and ecosystem health. Their occurrence has increased in frequency, duration, and severity over the last several decades. Preventing, controlling, or mitigating the impacts of HABs requires the development of permanent, operational ocean observing systems that continuously provide the data and information necessary for rapid detection and timely forecasts of changes in ecosystem states. Key elements of such observing systems are observations and modeling that must be efficiently linked via data management and communication networks. Building the observing system begins by integrating existing assets, is followed by incorporation of new technologies and knowledge, and is guided by the data and information needs of decision makers. User needs are particularly important for development of operational forecast models and new sensors for measuring required biological (e.g., HAB species abundance) and chemical (e.g., concentrations of HAB toxins) variables in near real time. This article describes operational observing system requirements for a HAB forecasting system and current efforts by Regional Associations to develop these observing systems for targeted species in their respective regions.

Excavations at Mask Cave on the sacred islet of Pulu off Mabuyag in the central west of Zenadh Kes (Torres Strait) reveal four occupational phases: Phase 1 (2900-3800 years ago), Phase 2 (2100-2600 years ago), Phase 3 (1500-1700 years ago) and Phase 4 (last 1500 years). Faunal remains indicate marine specialization (turtle and fish) during all phases. Petrographic analysis of sherds of finely made red-slipped pottery dating back 2400-2600 years reveals a unique fabric in terms of current understandings of Oceanic ceramic technologies. Mineral inclusions are consistent with local geology suggesting local manufacture and the existence of Indigenous Australia's first pottery tradition. Pre-ceramic Phase 1 is associated with demographic expansions across the western islands of Zenadh Kes by local populations of marine-based hunter-gatherers who were primarily Aboriginal language speakers. Phase 2 is associated with the immigration of Papuan maritime, horticultural and pottery-making peoples to the eastern and western islands of Zenadh Kes commencing 2600 years ago. Australian then Papuan settlement expansions across the western islands of Zenadh Kes explain why the local Western-Central Language has an Aboriginal base with a Papuan overlay. First colonization of the eastern islands by Papuans explains why the local Meriam Mir language is Papuan. Early red-slipped pottery in Zenadh Kes is linked to southern coastal Papuan pottery traditions that are reassessed to have a comparable 2600 year antiquity. Papuan settlement of the southern Papuan coast and Zenadh Kes was an extension of the post-Lapita settlement of the Pacific, an event memorialized in part by Torres Strait Islander oral tradition.

This paper reports the results of radiocarbon determinations on marine shell and charcoal excavated from archaeological sites on Mer and Dauar Islands in the eastern Torres Strait, Queensland. Commonly known as the Murray Islands, the group consists of the three small volcanic islands of Mer (Murray), Dauar and Waier. The Murray Islands Archaeological Project (MIAP) was initiated in 1998 and is being undertaken in collaboration with the Mer Island Community Council and traditional Meriam landowners. MIAP forms the basis of the author's doctoral research, with a major focus on determining the antiquity of human occupation of the islands, and the identification and timing of the development of the prehistoric horticultural economy (Carter et al. in press a,b). The dates reported here are the first to be recorded for the eastern Torres Strait region, and represent the first, reliable archaeological sequence of this antiquity in the wider Torres Strait. Â Dates are reported and discussed using uncalibrated radiocarbon age. Â

Background Microdeletion of the BP1-BP2 region on chromosome 15q11.2 is one of the most commonly reported copy number variants (CNVs) in the clinical population. It has been suggested that this deletion may impact cognitive, behavioural, and neurological function, as it has been observed with a higher frequency in patients being investigated for neurodevelopmental disorders (NDDs) than in controls. Retrospective case reports suffer from ascertainment bias and provide limited information about specific neurobehavioural deficits. Objectives Our study aims to collect detailed phenotypic data on proband and non-proband carriers of the 15q11.2 BP1-BP2 deletion, in particular the intellectual and behavioural profiles of these individuals. Design/method Families with at least one member with 15q11.2 BP1–2 deletion were recruited from clinicians. Participants were examined by a clinical geneticist, and a structured medical and family history was obtained. Psychometric and behavioural testing protocol included standardised measures of intelligence, language ability, autistic symptomatology, attention, and mental health. Results Results from the first eight participants are reported. Four participants fell within the Intellectually Disabled range (IQ Conclusions Our preliminary data shows that individuals with 15q11.2 deletion may be more likely to have ADHD, mild intellectual disability and articulation difficulties. Further study of additional probands and non-proband carriers is ongoing.

A previous experimental study (Reiss & McCowan, 1993) on dolphin vocal learning documented the process and pattern of vocal imitation in bottlenose dolphins (Tursiops truncatus). This previous study demonstrated that dolphins spontaneously imitate novel signals when paired with salient environmental events. The acquisition process of the dolphins’ imitations paralleled both the avian and human vocal development literature. Yet this past study did not directly test whether specific contingencies were necessary for vocal imitation by dolphins. The purpose of this study was to investigate the effects of contextual saliency on vocal imitation and acquisition in bottlenose dolphins. Over a six-month study period, we experimentally exposed two infant male bottlenose dolphins and their mothers to six novel computer-generated whistles that were either unpaired or paired with specific contextual events (preferred toy objects). The results demonstrate that acoustic exposure alone was sufficient for spontaneous vocal imitation to occur but that context affects the timing, extent and quality of vocal imitation by bottlenose dolphins.

A modification to the Pressure Sensitive Paint (PSP) method was used to visualize streamlines on a Blended Wing Body (BWB) model at full-scale flight Reynolds numbers. In order to achieve these conditions, the tests were carried out in the National Transonic Facility operating under cryogenic conditions in a nitrogen environment. Oxygen is required for conventional PSP measurements, and several tests have been successfully completed in nitrogen environments by injecting small amounts (typically < 3000 ppm) of oxygen into the flow. A similar technique was employed here, except that air was purged through pressure tap orifices already existent on the model surface, resulting in changes in the PSP wherever oxygen was present. The results agree quite well with predicted results obtained through computational fluid dynamics analysis (CFD), which show this to be a viable technique for visualizing flows without resorting to more invasive procedures such as oil flow or minitufts.

Aim : To examine the associations between connectedness to family and friends, and school engagement, and selected health compromising and health promoting behaviours in a sample of New Zealand adolescents. Methods : A web-based survey was designed and administered to a random sample of 652 Year 11 students aged 16 years from all Dunedin (NZ) high schools between 30th July and 31st October 2001. Connectedness to family and friends, and school engagement were assessed, together with reports of various health compromising and health promoting behaviours. Logistic regression was used to determine the extent to which these family, friends and school variables were related to health compromising and health promoting behaviours. Results : School engagement was strongly related to both low levels of health compromising and high levels of health promoting behaviours. Connectedness to family was associated primarily with fewer reports of suicidal ideation and increased reports of physical activity. Connectedness to friends was associated in the main with increased reports of health compromising behaviours. Conclusion : This study reinforces the importance of school and family as support networks for young people. School may well play an especially important role in health promotion among young people. The mechanisms by which engagement with school operates need to be explored further.

This paper reports the results of excavations conducted at the Mort Creek Site Complex, located in the Rodds Peninsula Section of Eurimbula National Park on the southern Curtis Coast, Central Queensland. Cultural and natural marine shell deposits were excavated and analysed as part of an investigation of natural and cultural site formation processes in the area. Analyses (including foraminifera studies) demonstrate a complex site formation history, with interfingering of cultural and natural shell deposits (cheniers) in some areas of the site. Radiocarbon dating indicates that Aboriginal occupation of the site was initiated before 2,000 cal BP, overlapping with dates obtained for natural chenier deposits.

This site report presents an account of archaeological excavations undertaken at Eurimbula Site 1, a large open midden site complex located in Eurimbula National Park on the southern Curtis Coast, Central Queensland. Excavations yielded a cultural assemblage dominated by mud ark (Anadara trapezia) and commercial oyster (Saccostrea commercialis) and incorporating small quantities of stone artefacts, fish bone and charcoal. Densities of cultural material were found to decrease markedly with distance from the creek. Analyses of excavated material demonstrate extensive low intensity use of the site from at least c.3,200 cal BP to the historical period.

In Australian archaeology distinguishing coastal shell midden deposits from natural shell formations has not been a simple task. Two of the principal contributors to this problem have been the ambiguous criteria of identification and the dynamic nature of Australia's coastal landscape. I investigate this issue by examining three marine shell deposits from Rodds Peninsula, on Central Queensland's Curtis Coast, excavated under the auspices of the Gooreng Gooreng Cultural Heritage Project. Field observations and preliminary research (Lilley et al. in press) which included the application of foraminiferal analysis, determined that both cultural and natural shell deposits had been excavated. In this thesis, the application of the two most credible criteria for the identification of shell deposits - species diversity and intra-specific size selection - demonstrate the complex nature of these deposits. This complexity is best demonstrated by the excavated assemblage of 'A7 ', which contains interwoven deposits of cultural and natural origins. My findings illustrate the integrity of the two conventional criteria applied, whilst highlighting both the credibility and need for refinement of foraminiferal analysis. Most importantly my research highlights the complexity of coastal environments and the broad implications they manifest for Australian archaeology.

Research in the discipline of antitrust economics, which encompasses legal as well as economic aspects, reveals a young and expanding area that has established its own literature within the past twenty years. The citations in this bibliographic essay were selected for their particular relevance to the subject and represent a core collection of materials that would be most useful to the study of American antitrust economics.