Performance of three-photon PET imaging: Monte Carlo simulations

We have recently introduced the idea of making use of three-photon positron annihilations in positron emission tomography. In this paper the basic characteristics of the three-gamma imaging in PET are studied by means of Monte Carlo simulations and analytical computations. Two typical configurations of human and small animal scanners are considered. Three-photon imaging requires high energy resolution detectors. Parameters currently attainable by CdZnTe semiconductor detectors, the technology of choice for the future development of radiation imaging, are assumed. Spatial resolution is calculated as a function of detector energy resolution and size, position in the field of view, scanner size, and the energies of the three gamma annihilation photons. Possible ways to improve the spatial resolution obtained for nominal parameters: 1.5 cm and 3.2 mm FWHM for human and small animal scanners, respectively, are indicated. Counting rates of true and random three-photon events for typical human and small animal scanning configurations are assessed. A simple formula for minimum size of lesions detectable in the three-gamma based images is derived. Depending on the contrast and total number of registered counts, lesions of a few mm size for human and sub mm for small animal scanners can be detected

Effects of FSH on testicular mRNA transcript levels in the hypogonadal mouse

FSH acts through the Sertoli cell to ensure normal testicular development and function. To identify transcriptional mechanisms through which FSH acts in the testis, we have treated gonadotrophin-deficient hypogonadal (hpg) mice with recombinant FSH and measured changes in testicular transcript levels using microarrays and real-time PCR 12, 24 and 72 h after the start of treatment. Approximately 400 transcripts were significantly altered at each time point by FSH treatment. At 12 h, there was a clear increase in the levels of a number of known Sertoli cell transcripts (e.g. Fabp5, Lgals1, Tesc, Scara5, Aqp5). Additionally, levels of Leydig cell transcripts were also markedly increased (e.g. Ren1, Cyp17a1, Akr1b7, Star, Nr4a1). This was associated with a small but significant rise in testosterone at 24 and 72 h. At 24 h, androgen-dependent Sertoli cell transcripts were up-regulated (e.g. Rhox5, Drd4, Spinlw1, Tubb3 and Tsx) and this trend continued up to 72 h. By contrast with the somatic cells, only five germ cell transcripts (Dkkl1, Hdc, Pou5f1, Zfp541 and 1700021K02Rik) were altered by FSH within the time-course of the experiment. Analysis of canonical pathways showed that FSH induced a general decline in transcripts related to formation and regulation of tight junctions. Results show that FSH acts directly and indirectly to induce rapid changes in Sertoli cell and Leydig cell transcript levels in the hpg mouse but that effects on germ cell development must occur over a longer time-span

Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH) is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH)-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI), 17β-hydroxysteroid dehydrogenase type III (17βHSD III), prostaglandin D (PGD)-synthetase and oestrogen sulphotransferase (EST)) is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH

Are healthcare costs from obesity associated with body mass index, comorbidity or depression? Cohort study using electronic health records

The objective of this study was to evaluate the association between body mass index (BMI) and healthcare costs in relation to obesity‐related comorbidity and depression. A population‐based cohort study was undertaken in the UK Clinical Practice Research Datalink (CPRD). A stratified random sample was taken of participants registered with general practices in England in 2008 and 2013. Person time was classified by BMI category and morbidity status using first diagnosis of diabetes (T2DM), coronary heart disease (CHD), stroke or malignant neoplasms. Participants were classified annually as depressed or not depressed. Costs of healthcare utilization were calculated from primary care records with linked hospital episode statistics. A two‐part model estimated predicted mean annual costs by age, gender and morbidity status. Linear regression was used to estimate the effects of BMI category, comorbidity and depression on healthcare costs. The analysis included 873 809 person‐years (62% female) from 250 046 participants. Annual healthcare costs increased with BMI, to a mean of £456 (95% CI 344–568) higher for BMI ≥40 kg m(−2) than for normal weight based on a general linear model. After adjusting for BMI, the additional cost of comorbidity was £1366 (£1269–£1463) and depression £1044 (£973–£1115). There was evidence of interaction so that as the BMI category increased, additional costs of comorbidity (£199, £74–£325) or depression (£116, £16–£216) were greater. High healthcare costs in obesity may be driven by the presence of comorbidity and depression. Prioritizing primary prevention of cardiovascular disease and diabetes in the obese population may contribute to reducing obesity‐related healthcare costs

On the Meridional Structure of Annular Modes

Using a simple stochastic model, the authors illustrate that the occurrence of a meridional dipole in the first empirical orthogonal function (EOF) of a time-dependent zonal jet is a simple consequence of the north–south excursion of the jet center, and this geometrical fact can be understood without appealing to fluid dynamical principles. From this it follows that one ought not, perhaps, be surprised at the fact that such dipoles, commonly referred to as the Arctic Oscillation (AO) or the Northern Annular Mode (NAM), have robustly been identified in many observational studies and appear to be ubiquitous in atmospheric models across a wide range of complexity

Sensory motor systems of artificial and natural hands

The surgeon Ambroise Paré designed an anthropomorphic hand for wounded soldiers in the 16th century. Since that time, there have been advances in technology through the use of computer-aided design, modern materials, electronic controllers and sensors to realise artificial hands which have good functionality and reliability. Data from touch, object slip, finger position and temperature sensors, mounted in the fingers and on the palm, can be used in feedback loops to automatically hold objects. A study of the natural neuromuscular systems reveals a complexity which can only in part be realised today with technology. Highlights of the parallels and differences between natural and artificial hands are discussed with reference to the Southampton Hand. The anatomical structure of parts of the natural systems can be made artificially such as the antagonist muscles using tendons. Theses solutions look promising as they are based on the natural form but in practice lack the desired physical specification. However, concepts of the lower spinal loops can be mimicked in principle. Some future devices will require greater skills from the surgeon to create the interface between the natural system and an artificial device. Such developments may offer a more natural control with ease of use for the limb deficient person

Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire

We provide a detailed description of the rutting vocalisations of free-ranging male Iberian deer (Cervus elaphus hispanicus, Hilzheimer 1909), a geographically isolated and morphologically differentiated subspecies of red deer Cervus elaphus. We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies. Iberian stags give bouts of roars (and more rarely, short series of barks) that are typically composed of two different types of calls. Long Common Roars are mostly given at the beginning or at the end of the bout, and are characterised by a high fundamental frequency (F0) resulting in poorly defined formant frequencies but a relatively high amplitude. In contrast, Short Common Roars are typically given in the middle or at the end of the bout, and are characterised by a lower F0 resulting in relatively well defined vocal tract resonances, but low amplitude. While we did not identify entirely Harsh Roars (as described in the Scottish red deer subspecies (Cervus elaphus scoticus), a small percentage of Long Common Roars contained segments of deterministic chaos. We suggest that the evolution of two clearly distinct types of Common Roars may reflect divergent selection pressures favouring either vocal efficiency in high pitched roars or the communication of body size in low-pitched, high spectral density roars highlighting vocal tract resonances. The clear divergence of the Iberian red deer vocal repertoire from those of other documented European red deer populations reinforces the status of this geographical variant as a distinct subspecies