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An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Unlike for many other respiratory infections, the seasonality of pertussis is not well understood. While evidence of seasonal fluctuations in pertussis incidence has been noted in some countries, there have been conflicting findings including in the context of Australia. We investigated this issue by analysing the seasonality of pertussis notifications in Australia using monthly data from January 1991 to December 2016. Data were made available for all states and territories in Australia except for the Australian Capital Territory and were stratified into age groups. Using a time-series decomposition approach, we formulated a generalised additive model where seasonality is expressed using cosinor terms to estimate the amplitude and peak timing of pertussis notifications in Australia. We also compared these characteristics across different jurisdictions and age groups. We found evidence that pertussis notifications exhibit seasonality, with peaks observed during the spring and summer months (November–January) in Australia and across different states and territories. During peak months, notifications are expected to increase by about 15% compared with the yearly average. Peak notifications for children <5 years occurred 1–2 months later than the general population, which provides support to the theory that older household members remain an important source of pertussis infection for younger children. In addition, our results provide a more comprehensive spatial picture of seasonality in Australia, a feature lacking in previous studies. Finally, our findings suggest that seasonal forcing may be useful to consider in future population transmission models of pertussis.
Many in the Christian tradition affirm two things: (1) that Jesus Christ descended to Hades/Limbus Patrum on Holy Saturday and (2) that the human nature of Jesus is a hylemorphic compound, the unity of a human soul and prime matter. I argue that (1) and (2) are incompatible; for the name ‘Jesus’, ‘Christ’, and ‘Jesus Christ’ rigidly designates a human being. But, given a certain view of hylemorphism, the human being, Jesus, ceased to exist in the time between his death and resurrection. So, Jesus did not descend to Hades/Limbus Patrum, even if God the Son did.
During its 2012 session the Florida Legislature amended the text of the Florida Statutes which lists exemptions from the requirements of obtaining a Florida drivers’ license. Removed from the text of Florida Statute 322.04 was the line concerning nonresidents, both fellow Americans and international visitors, “who has in his or her immediate possession a valid noncommercial driver's license issued to the nonresident in his or her home state or country [emphasis added].” Inserted was a new line, “An International Driving Permit issued in his or her name in his or her country of residence and a valid license issued in that country.” International visitors were required to have in their possession not only a valid drivers’ license, but also an International Driving Permit (IDP) that translated into English the personal identification information of the driver. The change took effect January 1, 2013, but even before that date, Florida faced allegations that it was violating international law with this new requirement.
Flow over a moderately swept wing is characterised by complex localised flow vortex topologies such as ‘closed’ separation bubbles or ‘open’ separation structures. A model of a complex cambered, twisted, tapered wing with 40° leading edge sweep, representative of those designed for manoeuvre at high subsonic Mach numbers, was investigated using the oil-film visualisation, stereo particle image velocimetry and force moment measurements. Wind-tunnel tests were conducted at a range of Reynolds number from 2.1×105 to 8.4×105 and at angles of incidence from −1° to 22°. Still images combined with video clips enable flow patterns over the wing model to be interpreted more clearly and accurately. Using successive images extracted from the video of flow visualisation, the movement of the oil pigment has been estimated. The influence of the Reynolds number and incidence angle was discussed through analysing the flow pattern over the wing surface. Additionally, the link between the flow structures present and the wing aerodynamic performance was studied.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
U60 ([UO2(O2)(OH)]6060− in water) is a uranyl peroxide nanocluster with a fullerene topology and Oh symmetry. U60 clusters can exist in crystalline solids or in liquids; however, little is known of their behavior at high pressures. We compressed the U60-bearing material: Li68K12(OH)20[UO2(O2)(OH)]60(H2O)310 (
; a = 37.884 Å) in a diamond anvil cell to determine its response to increasing pressure. Three length scales and corresponding structural features contribute to the compression response: uranyl peroxide bonds (<0.5 nm), isolated single nanoclusters (2.5 nm), and the long-range periodicity of nanoclusters within the solid (>3.7 nm). Li68K12(OH)20[UO2(O2)(OH)]60(H2O)310 transformed to a tetragonal structure below 2 GPa and irreversibly amorphized between 9.6 and 13 GPa. The bulk modulus of the tetragonal U60-bearing material was 25 ± 2 GPa. The pressure-induced amorphous phase contained intact U60 clusters, which were preserved beyond the loss of long-range periodicity. The persistence of U60 clusters at high pressure may have been enhanced by the interaction between U60 nanoclusters and the alcohol pressure medium. Once formed, U60 nanoclusters persist regardless of their associated long-range ordering—in crystals, amorphous solids, or solutions.
We have used the James Clerk Maxwell Telescope to observe 11 lines of SiCC with excitation energies up to 330 K above the ground state in IRC 10216. An excitation analysis indicates Trot = 43 ± 5 K within a given Ka ladder and Texc = 160 ± 50 K between Ka ladders. The column density of SiCC is estimated to be 3 × 1015 cm−2, more than an order of magnitude higher than previous estimates.
Results are presented from EXOSAT observations of Seyfert type active galactic nuclei (AGN). The sample chosen for study are 48 hard X-ray selected Seyfert type AGN, including all 30 of the emission line AGN in the Piccinotti sample. Combining EXOSAT LE and ME data has allowed us to obtain broad band X-ray spectra over the range 0.1–10 keV. Spectra in the ∼ 2–10 keV range are found to be well described by a simple power-law. The distribution of spectral indices across the sample can be approximated by a Gaussian distribution of mean energy index ∝ = 0.70 with σ∝ = 0.17 although not all individual spectra are consistent with this mean at the 90% confidence level. EXOSAT has also revealed a substantial number of sources with complex soft X-ray spectra. These include spectra with a second spectral component at soft X-ray energies and sources with “leaky” absorbing columns. Evidence that soft excess components occur in at least 50% of Seyfert type AGN together with detection of rapid variability in the soft component provides quantitative support for an accretion disc model for AGN.
Using the VLA, we obtained matched-array continuum observations at 6 and 2 cm. An angular resolution of ~1″ and an rms sensitivity of ~0.05 mJy were achieved for a sample of 17 nearby spiral galaxies. Spectral-index maps derived for the nuclear regions reveal a mixture of thermal and nonthermal activity. The use of high angular resolution and high frequencies was the key to the success in detecting thermal activity. Conversion from thermal fluxes to total number of ionizing photons suggests that star formation is very active in some of these cores (inner 500 pc), with a rate typically 10 times greater than in our own nuclear region. A number of the nuclear regions appear to be dominated by extended nonthermal emission with a steep spectrum. Among these, some are closely associated with thermal emission and hence are consistent with supernova activity. However there are sources exhibiting aligned structures, suggesting possible connections with a central active nucleus. In any case, at our achieved sensitivity level 16 out of 17 galaxies were detected in the radio continuum.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
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.
From June 15 to 28, 1991 the Compton Gamma-Ray Observatory (CGRO) observed the radio-loud quasar 3C 273. All four CGRO instruments detected radiation from this quasar in their relevant energy range (from 20 keV to 5 GeV). Simultaneous and quasi-simultaneous observations (spanning the time period May 27 – July 25, 1991) by instruments sensitive at other wavelengths have also been obtained. The data from all these observations spanning the frequency range from ∼ 109 Hz to ∼ 1026 Hz were collected and analysed. The resulting energy-density spectrum is shown in the figure below. It shows two maxima, one in the UV, another one at low-energy γ-rays which have nearly the same strength (the corresponding luminosities per decade of frequency for H0 = 60(km/s)/Mpc are 3.2·1046 erg/s and 2.7·1046 erg/s, respectively). A break of the spectrum at low-energy γ-rays is evident. From a detailed analysis a break energy of (2±1.5) MeV could be derived corresponding to a frequency of (4.8±3.6)·1020 Hz. The observed spectral break between X- and γ-rays is ∼ 0.8, much higher than the value of 0.5 predicted by some models. A more detailed paper on this topic is in preparation (Lichti et al.).
The reports of periodic X–ray emission from the Seyfert galaxy NGC 6814 have motivated a number of exotic models for the active nucleus. Our ROSAT observation shows that while the nucleus of NGC 6814 is indeed an X–ray emitter, the periodicity is due to another source, most likely a Galactic accreting binary system, ∼ 37 arc min away.
Aperiodic optical variability is a common property of Active Galactic Nuclei (AGN), though its physical origin is still open to question. We have compared light curves among the following two models and observation of quasar 0957+561A,B (Kundić et al. 1997) in terms of structure function analysis (§2).
Blazar OJ 287 is one of the best observed extragalactic objects. It's historical light curve goes back to 1890′s. Based on the historical behaviour Sillanpää et al. (1988) showed that OJ 287 displays large periodic outbursts, with a period of 11.7 years. We have monitored OJ 287 intensively for two years, during the OJ-94 project. This project was created for monitoring OJ 287 during its predicted new outburst in 1994. In the data archive we have over 7000 observations on OJ 287, in the radio, infrared and optical bands. This data archive contains the best ever obtained light curves for any extragalactic object. The optical light curve shows continuous variability down to time scales of tens of minutes. The variability observed in OJ 287 can be broken down to (at least) four different categories:
To limit tail biting incidence, most pig producers in Europe tail dock their piglets. This is despite EU Council Directive 2008/120/EC banning routine tail docking and allowing it only as a last resort. The paper aims to understand what it takes to fulfil the intentions of the Directive by examining economic results of four management and housing scenarios, and by discussing their consequences for animal welfare in the light of legal and ethical considerations. The four scenarios compared are: ‘Standard Docked’, a conventional housing scenario with tail docking meeting the recommendations for Danish production (0.7 m2/pig); ‘Standard Undocked’, which is the same as ‘Standard Docked’ but with no tail docking, ‘Efficient Undocked’ and ‘Enhanced Undocked’, which have increased solid floor area (0.9 and 1.0 m2/pig, respectively) provision of loose manipulable materials (100 and 200 g/straw per pig per day) and no tail docking. A decision tree model based on data from Danish and Finnish pig production suggests that Standard Docked provides the highest economic gross margin with the least tail biting. Given our assumptions, Enhanced Undocked is the least economic, although Efficient Undocked is better economically and both result in a lower incidence of tail biting than Standard Undocked but higher than Standard Docked. For a pig, being bitten is worse for welfare (repeated pain, risk of infections) than being docked, but to compare welfare consequences at a farm level means considering the number of affected pigs. Because of the high levels of biting in Standard Undocked, it has on average inferior welfare to Standard Docked, whereas the comparison of Standard Docked and Enhanced (or Efficient) Undocked is more difficult. In Enhanced (or Efficient) Undocked, more pigs than in Standard Docked suffer from being tail bitten, whereas all the pigs avoid the acute pain of docking endured by the pigs in Standard Docked. We illustrate and discuss this ethical balance using numbers derived from the above-mentioned data. We discuss our results in the light of the EU Directive and its adoption and enforcement by Member States. Widespread use of tail docking seems to be accepted, mainly because the alternative steps that producers are required to take before resorting to it are not specified in detail. By tail docking, producers are acting in their own best interests. We suggest that for the practice of tail docking to be terminated in a way that benefits animal welfare, changes in the way pigs are housed and managed may first be required.
It is well known that web-based interventions can be effective treatments for depression. However, dropout rates in web-based interventions are typically high, especially in self-guided web-based interventions. Rigorous empirical evidence regarding factors influencing dropout in self-guided web-based interventions is lacking due to small study sample sizes. In this paper we examined predictors of dropout in an individual patient data meta-analysis to gain a better understanding of who may benefit from these interventions.
A comprehensive literature search for all randomized controlled trials (RCTs) of psychotherapy for adults with depression from 2006 to January 2013 was conducted. Next, we approached authors to collect the primary data of the selected studies. Predictors of dropout, such as socio-demographic, clinical, and intervention characteristics were examined.
Data from 2705 participants across ten RCTs of self-guided web-based interventions for depression were analysed. The multivariate analysis indicated that male gender [relative risk (RR) 1.08], lower educational level (primary education, RR 1.26) and co-morbid anxiety symptoms (RR 1.18) significantly increased the risk of dropping out, while for every additional 4 years of age, the risk of dropping out significantly decreased (RR 0.94).
Dropout can be predicted by several variables and is not randomly distributed. This knowledge may inform tailoring of online self-help interventions to prevent dropout in identified groups at risk.