Delayed reception of live blowfly (Calliphora vicina and Chrysomya rufifacies) larval samples: implications for minimum postmortem interval estimates.

Forensic entomology evidence collected by police and mortuary staff may be delayed in getting to the entomologist. Live samples may continue developing and alter minimum postmortem interval (PMImin) estimates. This study investigated development of simulated evidential samples of Calliphora vicina Robineau-Desvoidy and Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) maggots. Maggots of each species were studied in three developmental classes: "small" (late second/early third instar), "mid" (mid third instar) and "large" (late third instar). Seven replicates of 11 maggots in each class were assigned without food to four treatments: (1) 24 h at 20 °C; (2) 24 h at 4 °C; (3) 48 h at 20 °C and (4) 48 h at 4 °C. There was a significant difference in absolute length change across treatments, reflecting size for C. vicina, and interaction between size, time and temperature for Ch. rufifacies. Calliphora vicina maggots showed minimal mortality, and most second instar larvae moulted by the experiment's end. Chrysomya rufifacies showed heavy mortality and minimal moulting from the second to third instar. Only "large" Ch. rufifacies maggots kept at room temperature for 48 h pupariated. Since these results confirm that development can continue in live unfed maggot samples after their collection, it is not advisable to delay their preservation

Climate Dynamics: A Network-Based Approach for the Analysis of Global Precipitation

Precipitation is one of the most important meteorological variables for defining the climate dynamics, but the spatial patterns of precipitation have not been fully investigated yet. The complex network theory, which provides a robust tool to investigate the statistical interdependence of many interacting elements, is used here to analyze the spatial dynamics of annual precipitation over seventy years (1941-2010). The precipitation network is built associating a node to a geographical region, which has a temporal distribution of precipitation, and identifying possible links among nodes through the correlation function. The precipitation network reveals significant spatial variability with barely connected regions, as Eastern China and Japan, and highly connected regions, such as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe. Sahel and Eastern Australia are remarkably dry regions, where low amounts of rainfall are uniformly distributed on continental scales and small-scale extreme events are rare. As a consequence, the precipitation gradient is low, making these regions well connected on a large spatial scale. On the contrary, the Asiatic South-East is often reached by extreme events such as monsoons, tropical cyclones and heat waves, which can all contribute to reduce the correlation to the short-range scale only. Some patterns emerging between mid-latitude and tropical regions suggest a possible impact of the propagation of planetary waves on precipitation at a global scale. Other links can be qualitatively associated to the atmospheric and oceanic circulation. To analyze the sensitivity of the network to the physical closeness of the nodes, short-term connections are broken. The African Sahel, Eastern Australia and Northern Europe regions again appear as the supernodes of the network, confirming furthermore their long-range connection structure. Almost all North-American and Asian nodes vanish, revealing that extreme events can enhance high precipitation gradients, leading to a systematic absence of long-range patterns

Radiation management and credentialing of fluoroscopy users

During the last 15 years, developments in X-ray technologies have substantially improved the ability of practitioners to treat patients using fluoroscopically guided interventional techniques. Many of these procedures require a greater use of fluoroscopy and more recording of images. This increases the potential for radiation-induced dermatitis and epilation, as well as severe radiation-induced burns to patients. Many fluoroscope operators are untrained in radiation management and do not realize that these procedures increase the risk of radiation injury and radiation-induced cancer in personnel as well as patients. The hands of long-time fluoroscope operators in some cases exhibit radiation damage—especially when sound radiation protection practices have not been followed. In response, the Center for Devices and Radiological Health of the United States Food and Drug Administration has issued an Advisory calling for proper training of operators. Hospitals and administrators need to support and enforce the need for this training by requiring documentation of credentials in radiation management as a prerequisite for obtaining fluoroscopy privileges. A concerted effort on the part of professional medical organizations and regulatory agencies will be required to train fluoroscopy users to prevent physicians from unwittingly imparting serious radiation injuries to their patients

Absent cervical spine pedicle and associated congenital spinal abnormalities - a diagnostic trap in a setting of acute trauma: case report

BACKGROUND: Congenital spinal abnormalities can easily be misdiagnosed on plain radiographs. Additional imaging is warranted in doubtful cases, especially in a setting of acute trauma. Case Presentation This patient presented at the emergency unit of our university hospital after a motor vehicle accident and was sent to our radiology department for imaging of the cervical spine. Initial clinical examination and plain radiographs of the cervical spine were performed but not conclusive. Additional CT of the neck helped establish the right diagnosis. CONCLUSION: CT as a three-dimensional imaging modality with the possibility of multiplanar reconstructions allows for the exact diagnosis and exclusion of acute traumatic lesions of the cervical spine, especially in cases of doubtful plain radiographs and when congenital spinal abnormalities like absent cervical spine pedicle with associated spina bifida may insinuate severe trauma

Ecologic Niche Modeling of Blastomyces dermatitidis in Wisconsin

Background: Blastomycosis is a potentially fatal mycosis that is acquired by inhaling infectious spores of Blastomyces dermatitidis present in the environment. The ecology of this pathogen is poorly understood, in part because it has been extremely difficult to identify the niche(s) it occupies based on culture isolation of the organism from environmental samples. Methodology/Principal Findings: We investigated the ecology of blastomycosis by performing maximum entropy modeling of exposure sites from 156 cases of human and canine blastomycosis to provide a regional-scale perspective of the geographic and ecologic distribution of B. dermatitidis in Wisconsin. Based on analysis with climatic, topographic, surface reflectance and other environmental variables, we predicted that ecologic conditions favorable for maintaining the fungus in nature occur predominantly within northern counties and counties along the western shoreline of Lake Michigan. Areas of highest predicted occurrence were often in proximity to waterways, especially in northcentral Wisconsin, where incidence of infection is highest. Ecologic conditions suitable for B. dermatitidis are present in urban and rural environments, and may differ at the extremes of distribution of the species in the state. Conclusions/Significance: Our results provide a framework for a more informed search for specific environmental factors modulating B. dermatitidis occurrence and transmission and will be useful for improving public health awareness of relativ

Accuracy of Doppler-Echocardiographic Mean Pulmonary Artery Pressure for Diagnosis of Pulmonary Hypertension

Background: The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. Methodology/Principal Findings: 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r = 0.93) and not sPAP (r = 0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP$25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n = 50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98 % and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. Conclusion: mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation-in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company's economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company's economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company's model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations

Performance of Ultra-Deep Pyrosequencing in Analysis of HIV-1 pol Gene Variation

INTRODUCTION: Ultra-deep pyrosequencing (UDPS) has been used to detect minority variants within HIV-1 populations. Some aspects of the quality and reproducibility of UDPS have been previously evaluated, but comprehensive studies are still needed. PRINCIPAL FINDING: In this study the UDPS technology (FLX platform) was evaluated by analyzing a 120 base pair fragment of the HIV-1 pol gene from plasma samples from two patients and artificial mixtures of molecular clones. UDPS was performed using an optimized experimental protocol and an in-house data cleaning strategy. Nine samples and mixtures were analyzed and the average number of reads per sample was 19,404 (range 8,858-26,846). The two patient plasma samples were analyzed twice and quantification of viral variants was found to be highly repeatable for variants representing >0.27% of the virus population, whereas some variants representing 0.11-0.27% were detected in only one of the two UDPS runs. Bland-Altman analysis showed that a repeated measurement would have a 95% likelihood to lie approximately within ±0.5 log(10) of the initial estimate. A similar level of agreement was observed for variant frequency estimates in forward vs. reverse sequencing direction, but here the agreement was higher for common variants than for rare variants. UDPS following PCR amplification with alternative primers indicated that some variants may be incorrectly quantified due to primer-related selective amplification. Finally, the in vitro recombination rate during PCR was evaluated using artificial mixtures of clones and was found to be low. The most abundant in vitro recombinant represented 0.25% of all UDPS reads. CONCLUSION: This study demonstrates that this UDPS protocol results in low experimental noise and high repeatability, which is relevant for future research and clinical use of the UDPS technology. The low rate of in vitro recombination suggests that this UDPS system can be used to study genetic variants and mutational linkage