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Our understanding about the genetic influences on human disease has increased dramatically with the technological developments in genome and DNA analysis and the discovery of the human genome sequence. Whilst much remains unexplained, it is obvious that normal cardiac development is controlled by the genome and there is significant evidence that a proportion of cardiac malformations are caused by genetic factors. This is important for clinicians as an understanding of confirmed genetic factors is essential to estimate recurrence risks of congenital heart disease (CHD) within families and also screen for predicted associated anomalies. An accurate genetic diagnosis can provide important prognostic information for both the initial patient (proband) and other family members, for whom further genetic investigations may be indicated. There is likely to be a continued increase in demand for such investigations as improvement in surgical and medical management allows more individuals with CHD to survive to reproductive age and have families of their own. For some, the recurrence risk for a cardiac malformation may be as high as 50%; the actual figure varies with different genetic diagnoses. Accurate risk stratification is likely to become increasingly important and the rapidly developing technologies to detect genetic variation mean that genome-wide investigation is becoming more widely available in the clinical setting. An aim of this chapter is to introduce clinicians to principles that will help them embrace and understand the results from these investigations and appreciate the implications they have for their patients.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
Three new Llandovery (early Silurian) crinoids from Estonia provide an improved understanding of the paleogeographic aspects of the crinoid diversification following the end-Ordovician extinctions. The new taxa are Euspirocrinus hintsae new species (Rhuddanian eucladid), Oepikicrinus perensae new genus new species (Aeronian camerate), and Rozhnovicrinus isakarae new genus new species (Aeronian eucladid). This brings the total of described Llandovery crinoids in Estonia to eight nominal species and a further three taxa in open nomenclature. The Rhuddanian radiation in Baltica mirrored that on Laurentia and Avalonia and was dominated by Ordovician clades that continued to diversify during the Silurian. Known Aeronian crinoids from Estonia continue these clades, whereas new clades diversified on Laurentia and Avalonia. However, by the Wenlock, a largely cosmopolitan fauna existed on Laurentia, Avalonia, and Baltica.
People with cerebral palsy (CP) are less physically active than the general population and, consequently, are at increased risk of preventable disease. Evidence indicates that low-moderate doses of physical activity can reduce disease risk and improve fitness and function in people with CP. Para athletes with CP typically engage in ‘performance-focused’ sports training, which is undertaken for the sole purpose of enhancing sports performance. Anecdotally, many Para athletes report that participation in performance-focused sports training confers meaningful clinical benefits which exceed those reported in the literature; however, supporting scientific evidence is lacking. The aim of this paper is to describe the protocol for an 18-month study evaluating the clinical effects of a performance-focused swimming training programme for people with CP who have high support needs.
This study will use a concurrent multiple-baseline, single-case experimental design across three participants with CP who have high support needs. Each participant will complete a five-phase trial comprising: baseline (A1); training phase 1 (B1); maintenance phase 1 (A2); training phase 2 (B2); and maintenance phase 2 (A3). For each participant, measurement of swim velocity, health-related quality of life and gross motor functioning will be carried out a minimum of five times in each of the five phases.
The study described will produce Level II evidence regarding the effects of performance-focused swimming training on clinical outcomes in people with CP who have high support needs. Findings are expected to provide an indication of the potential for sport to augment outcomes in neurological rehabilitation.
The Kalana Lagerstätte of early Aeronian (Llandovery, Silurian) age in central Estonia preserves a diverse shallow marine biota dominated by non-calcified algae. This soft-tissue flora and decalcified and calcified crinoids are preserved in situ, in a lens of microlaminated, dolomitized micrite interbedded in a sequence of dolomitized packstones and wackestones. Although the Lagerstätte is dominated by non-calcified algae, crinoids (together with brachiopods and gastropods) are among the most common organisms that were originally comprised of a carbonate skeleton. Two new crinoids are described from this unit, Kalanacrinus mastikae n. gen. n. sp. (large camerate) and Tartucrinus kalanaensis n. gen. n. sp. (small disparid). Interestingly, these two crinoids display contrasting preservation, with the more common large camerate preserved primarily as a decalcified organic residue, whereas the smaller disparid is preserved primarily in calcite. Preservation was assessed using elemental mapping of C, Ca, S, and Si. Columns have the highest portion of Ca, once living soft tissue is indicated by C, S was dispersed as pyrite or associated with organics, and Si is probably associated with clay minerals in the matrix. This new fauna increases our understanding of the crinoid radiation on Baltica following Late Ordovician extinctions.
The escalating conflicts in the Middle East have been associated with the rapid collapse of the existing healthcare systems in affected countries. As millions of refugees flee their countries, they become vulnerable and exposed to communicable diseases that easily grow into epidemic crises. Here, we describe infectious disease epidemics that have been associated with conflicts in the Middle East, including cholera, poliomyelitis, measles, cutaneous leishmaniasis, and diphtheria, that call for appropriate preventive measures. Local ongoing wars and failing healthcare systems have resulted in regional and global health threats that warrant international medical interventions.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Post-traumatic stress disorder (PTSD) is often associated with attention allocation and emotional regulation difficulties, but the brain dynamics underlying these deficits are unknown. The emotional Stroop task (EST) is an ideal means to monitor these difficulties, because participants are asked to attend to non-emotional aspects of the stimuli. In this study, we used magnetoencephalography (MEG) and the EST to monitor attention allocation and emotional regulation during the processing of emotionally charged stimuli in combat veterans with and without PTSD.
A total of 31 veterans with PTSD and 20 without PTSD performed the EST during MEG. Three categories of stimuli were used, including combat-related, generally threatening and neutral words. MEG data were imaged in the time-frequency domain and the network dynamics were probed for differences in processing threatening and non-threatening words.
Behaviorally, veterans with PTSD were significantly slower in responding to combat-related relative to neutral and generally threatening words. Veterans without PTSD exhibited no significant differences in responding to the three different word types. Neurophysiologically, we found a significant three-way interaction between group, word type and time period across multiple brain regions. Follow-up testing indicated stronger theta-frequency (4–8 Hz) responses in the right ventral prefrontal (0.4–0.8 s) and superior temporal cortices (0.6–0.8 s) of veterans without PTSD compared with those with PTSD during the processing of combat-related words.
Our data indicated that veterans with PTSD exhibited deficits in attention allocation and emotional regulation when processing trauma cues, while those without PTSD were able to regulate emotion by directing attention away from threat.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Rhuddanian crinoid faunas are poorly known globally, making this new fauna from the Hilliste Formation of western Estonian especially significant. The Hilliste fauna is the oldest Silurian fauna known from the Baltica paleocontinent, thus this is the first example of the crinoid recovery fauna after the Late Ordovician mass extinction. Hiiumaacrinus vinni n. gen. n. sp., Protaxocrinus estoniensis n. sp., Eomyelodactylus sp., calceocrinids, and five holdfast types are reported here. Although the fauna has relatively few taxa, it is among the most diverse Rhuddanian faunas known. Similar to other Rhuddanian crinoid faunas elsewhere, the Hilliste crinoid fauna contains crinoids belonging the Dimerocrinitidae, Taxocrinidae, Calceocrinidae, and Myelodactylidae; most elements of the new fauna are quite small, perhaps indicative of the Lilliput Effect.
The Molonglo Observatory Synthesis Telescope (MOST) has been used to observe the Sun with total-power fan-beams having a one-dimensional resolution of 41 arcsec at 843 MHz. The scans reveal clearly the rotation and evolution of the slowly-varying component as well as some burst activity. Low radio brightness features have also been identified, but the exact relationship between these features and coronal holes is, as yet, unclear. Several partial synthesis observations have been used to generate two-dimensional radioheliograms.
There has been considerable speculation in recent years about the evolution of radio galaxies in clusters. The discovery of powerful X-ray emission with an apparently thermal spectrum from a considerable number of clusters has been attributed to a hot (108K) intracluster gas with an electron density of ∼ 10-3 cm -3 at the cluster centre (see e.g. McHardy 1978). Such a gas surrounding a radio galaxy may conceivably retard the expansion or diffusion of the relativistic electrons and thus allow the source to retain its identity for longer intervals than is the case for field galaxies.
The Molonglo Observatory Synthesis Telescope (MOST), which at present images a fully synthesised 70′ field in 12 h, is being converted to enable observing modes which extend the field size to 160′. The new observing modes will allow the MOST to survey completely the sky south of δ = −30° to a (5σ) sensitivity limit of about 5 mJy. The result will be a catalogue of over 400,000 radio sources with a spatial density of less than 1 source per 100 beam areas, providing the foundation for a number of novel astronomical and cosmological investigations. The conversion involves construction of 352 low-noise HEMT preamplifiers, 88 digitally controlled UHF quad phase shifters, 88 mixers and IF sections, a new communication and control system, and several other new sub-systems. The project has been funded and developments are well advanced.
During 1990 we surveyed the southern sky using a multi-beam receiver at frequencies of 4850 and 843 MHz. The half-power beamwidths were 4 and 25 arcmin respectively. The finished surveys cover the declination range between +10 and −90 degrees declination, essentially complete in right ascension, an area of 7.30 steradians. Preliminary analysis of the 4850 MHz data indicates that we will achieve a five sigma flux density limit of about 30 mJy. We estimate that we will find between 80 000 and 90 000 new sources above this limit. This is a revised version of the paper presented at the Regional Meeting by the first four authors; the surveys now have been completed.
We have assembled a new sample of some of the most FIR-luminous galaxies in the Universe and have imaged them in 1.1 mm dust emission and measured their redshifts 1 < z < 4 via CO emission lines using the 32-m Large Millimeter Telescope / Gran Telescopio Milimétrico (LMT/GTM). Our sample of 31 submm galaxies (SMGs), culled from the Planck and Herschel all-sky surveys, includes 14 of the 21 most luminous galaxies known, with LFIR > 1014L⊙ and SFR > 104M⊙/yr. These extreme inferred luminosities – and multiple / extended 1.1 mm images – imply that most or all are strongly gravitationally lensed, with typical magnification μ ~ 10 × . The gravitational lensing provides two significant benefits: (1) it boosts the S/N, and (2) it allows investigation of star formation and gas processes on sub-kpc scales.
To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5±6.4 years) in the Brain in Motion Study, completed the Lifetime Total Physical Activity Questionnaire and underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Post hoc analyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p<.0001). Cerebrovascular measures did not mediate the association between PA and global cognition scores (p>.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function. (JINS, 2015, 21, 816–830)
We have conducted 1.1 mm ALMA observations of a contiguous 105” × 50” or 1.5 arcmin2 window in the SXDF-UDS-CANDELS. We achieved a 5σ sensitivity of 0.28 mJy, giving a flat sensus of dusty star-forming galaxies with LIR ~6×1011L⊙ (if Tdust=40K) up to z ~ 10 thanks to the negative K-correction at this wavelength. We detected 5 brightest sources (S/N>6) and 18 low-significant sources (5>S/N>4; they may contain spurious detections, though). One of the 5 brightest ALMA sources (S1.1mm = 0.84 ± 0.09 mJy) is extremely faint in the WFC3 and VLT/HAWK-I images, demonstrating that a contiguous ALMA imaging survey uncovers a faint dust-obscured population invisible in the deep optical/near-infrared surveys. We find a possible [CII]-line emitter at z=5.955 or a low-z CO emitting galaxy within the field, allowing us to constrain the [CII] and/or CO luminosity functions across the history of the universe.
The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.