The current status of the case report: Terminal or viable?

The case report, which has a long history in medicine, has seen its fortune wax and wane with time. We discuss the challenges facing the continued survival of the case report, including the inability of journals to cope with the increased load and increased cost of publication, ethical issues, the impact factor and the rise of evidence-based medicine. We highlight the important role that the case report will continue to play in medical research and education, as a means of sharing information and detecting novelty through observations. Most importantly, the case report serves as a stepping stone for young physicians and practitioners into the world of medical writing

A Homolog of the Vaccinia Virus D13L Rifampicin Resistance Gene is in the Entomopoxvirus of the Parasitic wasp, Diachasmimorpha longicaudata

The parasitic wasp, Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae), introduces an entomopoxvirus (DlEPV) into its Caribbean fruit fly host, Anastrepha suspensa. (Loew) (Diptera: Tephritidae), during oviposition. DlEPV has a 250–300 kb unipartite dsDNA genome, that replicates in the cytoplasm of the host's hemocytes, and inhibits the host's encapsulation response. The putative proteins encoded by several DlEPV genes are highly homologous with those of poxviruses, while others appear to be DlEPV specific. Here, a 2.34 kb sequence containing a 1.64 kb DlEPV open reading frame within a cloned 4.5 kb EcoR1 fragment (designated R1–1) is described from a DlEPV EcoRI genomic library. This open reading frame is a homolog of the vaccinia virus rifampicin resistance (rif) gene, D13L, and encodes a putative 546 amino acid protein. The DlEPV rif contains two EcoRV, two HindIII, one XbaI, and one DraII restriction sites, and upstream of the open reading frame the fragment also contains EcoRV, HindII, SpEI, and BsP106 sites. Early poxvirus transcription termination signals (TTTTTnT) occur 236 and 315 nucleotides upstream of the consensus poxvirus late translational start codon (TAAATG) and at 169 nucleotides downstream of the translational stop codon of the rif open reading frame. Southern blot hybridization of HindIII-, EcoRI-, and BamH1-restricted DlEPV genomic DNA probed with the labeled 4.5 kb insert confirmed the fidelity of the DNA and the expected number of fragments appropriate to the restriction endonucleases used. Pairwise comparisons between DlEPV amino acids and those of the Amsacta moorei, Heliothis armigera, and Melanoplus sanguinipes entomopoxviruses, revealed 46, 46, and 45 % similarity (identity + substitutions), respectively. Similar values (41–45%) were observed in comparisons with the chordopoxviruses. The mid portion of the DlEPV sequence contained two regions of highest conserved residues similar to those reported for H. armigera entomopoxvirus rifampicin resistance protein. Phylogenetic analysis of the amino acid sequences suggested that DlEPV arose from the same ancestral node as other entomopoxviruses but belongs to a separate clade from those of the grasshopper- infecting M. sanguinipes entomopoxvirus and from the Lepidoptera-infecting (Genus B or Betaentomopoxvirus) A. moorei entomopoxvirus and H. armigera entomopoxvirus. Interestingly, the DlEPV putative protein had only 3–26.4 % similarity with RIF-like homologs/orthologs found in other large DNA non-poxviruses, demonstrating its closer relationship to the Poxviridae. DlEPV remains an unassigned member of the Entomopoxvirinae (http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm) until its relationship to other diptera-infecting (Gammaentomopoxvirus or Genus C) entomopoxviruses can be verified. The GenBank accession number for the nucleotide sequence data reported in this paper is EF541029

RNA:protein ratio of the unicellular organism as a characteristic of phosphorous and nitrogen stoichiometry and of the cellular requirement of ribosomes for protein synthesis

Background Mean phosphorous:nitrogen (P:N) ratios and relationships of P:N ratios with the growth rate of organisms indicate a surprising similarity among and within microbial species, plants, and insect herbivores. To reveal the cellular mechanisms underling this similarity, the macromolecular composition of seven microorganisms and the effect of specific growth rate (SGR) on RNA:protein ratio, the number of ribosomes, and peptide elongation rate (PER) were analyzed under different conditions of exponential growth. Results It was found that P:N ratios calculated from RNA and protein contents in these particular organisms were in the same range as the mean ratios reported for diverse organisms and had similar positive relationships with growth rate, consistent with the growth-rate hypothesis. The efficiency of protein synthesis in microorganisms is estimated as the number of active ribosomes required for the incorporation of one amino acid into the synthesized protein. This parameter is calculated as the SGR:PER ratio. Experimental and theoretical evidence indicated that the requirement of ribosomes for protein synthesis is proportional to the RNA:protein ratio. The constant of proportionality had the same values for all organisms, and was derived mechanistically from the characteristics of the protein-synthesis machinery of the cell (the number of nucleotides per ribosome, the average masses of nucleotides and amino acids, the fraction of ribosomal RNA in the total RNA, and the fraction of active ribosomes). Impairment of the growth conditions decreased the RNA:protein ratio and increased the overall efficiency of protein synthesis in the microorganisms. Conclusion Our results suggest that the decrease in RNA:protein and estimated P:N ratios with decrease in the growth rate of the microorganism is a consequence of an increased overall efficiency of protein synthesis in the cell resulting from activation of the general stress response and increased transcription of cellular maintenance genes at the expense of growth related genes. The strong link between P:N stoichiometry, RNA:protein ratio, ribosomal requirement for protein synthesis, and growth rate of microorganisms indicated by the study could be used to characterize the N and P economy of complex ecosystems such as soils and the oceans

Impact of the physical-chemical properties of poly(lactic acid)-poly (ethylene glycol) polymeric nanoparticles on biodistribution

Nanoparticle (NP) formulations are inherently polydisperse making their structural characterization and justification of specifications complex. It is essential, however, to gain an understanding of the physico-chemical properties that drive performance in vivo. To elucidate these properties, drug-containing poly(lactic acid) (PLA)–poly(ethylene glycol) (PEG) block polymeric NP formulations (or PNPs) were sub-divided into discrete size fractions and analyzed using a combination of advanced techniques, namely cryogenic transmission electron microscopy, small-angle neutron and X-ray scattering, nuclear magnetic resonance, and hard-energy X-ray photoelectron spectroscopy. Together, these techniques revealed a uniquely detailed picture of PNP size, surface structure, internal molecular architecture and the preferred site(s) of incorporation of the hydrophobic drug, AZD5991, properties which cannot be accessed via conventional characterization methodologies. Within the PNP size distribution, it was shown that the smallest PNPs contained significantly less drug than their larger sized counterparts, reducing overall drug loading, while PNP molecular architecture was critical in understanding the nature of in vitro drug release. The effect of PNP size and structure on drug biodistribution was determined by administrating selected PNP size fractions to mice, with the smaller sized NP fractions increasing the total drug-plasma concentration area under the curve and reducing drug concentrations in liver and spleen, due to greater avoidance of the reticuloendothelial system. In contrast, administration of unfractionated PNPs, containing a large population of NPs with extremely low drug load, did not significantly impact the drug's pharmacokinetic behavior - a significant result for nanomedicine development where a uniform formulation is usually an important driver. We also demonstrate how, in this study, it is not practicable to validate the bioanalytical methodology for drug released in vivo due to the NP formulation properties, a process which is applicable for most small molecule-releasing nanomedicines. In conclusion, this work details a strategy for determining the effect of formulation variability on in vivo performance, thereby informing the translation of PNPs, and other NPs, from the laboratory to the clinic.</p

Repetitive Behavior in Rubinstein–Taybi Syndrome:Parallels with Autism Spectrum Phenomenology

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein–Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS

Brexit and the everyday politics of emotion: methodological lessons from history

The 2016 European Union referendum campaign has been depicted as a battle between ‘heads’ and ‘hearts’, reason and emotion. Voters’ propensity to trust their feelings over expert knowledge has sparked debate about the future of democratic politics in what is increasingly believed to be an ‘age of emotion’. In this article, we argue that we can learn from the ways that historians have approached the study of emotions and everyday politics to help us make sense of this present moment. Drawing on William Reddy’s concept of ‘emotional regimes’, we analyse the position of emotion in qualitative, ‘everyday narratives’ about the 2016 European Union referendum. Using new evidence from the Mass Observation Archive, we argue that while reason and emotion are inextricable facets of political decision-making, citizens themselves understand the two processes as distinct and competing

Extinction of eastern Sahul megafauna coincides with sustained environmental deterioration

Abstract: Explanations for the Upper Pleistocene extinction of megafauna from Sahul (Australia and New Guinea) remain unresolved. Extinction hypotheses have advanced climate or human-driven scenarios, in spite of over three quarters of Sahul lacking reliable biogeographic or chronologic data. Here we present new megafauna from north-eastern Australia that suffered extinction sometime after 40,100 (±1700) years ago. Megafauna fossils preserved alongside leaves, seeds, pollen and insects, indicate a sclerophyllous forest with heathy understorey that was home to aquatic and terrestrial carnivorous reptiles and megaherbivores, including the world’s largest kangaroo. Megafauna species diversity is greater compared to southern sites of similar age, which is contrary to expectations if extinctions followed proposed migration routes for people across Sahul. Our results do not support rapid or synchronous human-mediated continental-wide extinction, or the proposed timing of peak extinction events. Instead, megafauna extinctions coincide with regionally staggered spatio-temporal deterioration in hydroclimate coupled with sustained environmental change

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Planck 2015 results. XXVII. The Second Planck Catalogue of Sunyaev-Zeldovich Sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest all-sky catalogue of galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data-sets, and is the first SZ-selected cluster survey containing > $10^3$ confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the Y5R500 estimates are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires. the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical and X-ray data-sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under- luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples