Neurological pain relief interventional radiology procedures.

Neurological interventions have taken on a significant role in interventional radiology (IR) practice. Indications fall under three main categories: (1) intraprocedural pain management, (2) cancer pain palliation, and (3) chronic non-cancer pain control. Short-term regional anaesthesia can be achieved with local anaesthetics, while longer-term pain control can be attained with radiofrequency neuromodulation (pulsed or otherwise) or thermal/chemical neurolysis. This review article summarises the therapeutic options, applications, and techniques of commonly used peripheral nerve and plexus interventions in IR.

Validation of a three-dimensionally printed simulator for training in endoscopic sinonasal surgery.

BACKGROUND: The ability to incorporate different materials in the construction of 3-D printed models has resulted in the ability to mimic a variety of anatomical structures such as cartilage, mucosa and bone. The aim of this study was to evaluate the face and content validities of a model as a training tool for endoscopic sinus surgery. METHODS: Twenty-six delegates and ten teaching faculty members were invited to complete a post-hoc questionnaire survey. The survey consisted of a 22-question 5-point Likert scale to assess the model's realism (face validity) and its effectiveness as a training tool (content validity). RESULTS: Over 80% of the delegates agreed or strongly agreed that the appearance of anatomical structures within the model was realistic and mimicked actual sinus anatomy. In addition, a similar proportion agreed or strongly agreed that the application of instruments on the composite materials of the model realistically mimicked bone. All faculty agreed that the model was useful to develop hand-eye coordination and was a useful training tool for endoscopic sinus surgery. Overall, the sinus model received high scores regarding its use for training surgeons, especially to develop camera and instrument handling skills. CONCLUSION: The results of this study suggest that otolaryngology doctors in their early or intermediate stage of training would benefit most from a clinical-based modular programme. The model requires further development in areas such as the realism of mucosa, incorporation of sinonasal pathology and having more complex anatomy to be useful for the training of more advanced surgeons.

Octyl cyanoacrylate skin adhesive with or without subcuticular suture for skin closure after implantable venous port placement for oncology patients: a propensity-score matching analysis.

AIM: To compare peri-operative outcomes of skin closure with octyl cyanoacrylate (OCA) skin adhesive (Dermabond) with or without subcuticular sutures after deep dermal suturing for implantable venous port placement closure. MATERIALS AND METHODS: Seven hundred and ninety-two single-lumen implantable venous port insertions for chemotherapy were reviewed from September 2019 to March 2021 in a retrospective single-centre study. Propensity-score matching by a 1:1 nearest neighbour algorithm was conducted to control for confounding baseline differences. Distances were determined by logistic regression. Propensity-score matching was performed based on the following variables: age at procedure, gender, race, operator's seniority, use of anchoring polypropylene suture (PROLENE), port model, and volume of intra-operative local analgesia. The primary outcome was wound dehiscence at the first follow-up (∼1 week). RESULTS: The 792 port insertions were conducted in 302 males (38.1%), median age 63 years (IQR: 54-69). Of the 656 wounds closed with subcuticular sutures and skin adhesive, 136 were matched in a 1:1 fashion against procedures closed without a subcuticular suture. No significant differences were demonstrated in pain scores, bleeding, swelling, bruising, fever, wound dehiscence, and discharge at postoperative day 1 (POD1) and at first follow-up between the groups (all p>0.05). Of note, no significant differences in wound dehiscence at first follow-up was found in both unmatched (p=0.133) and matched cohorts (McNemar-Bowker's χ2 = 1.167, p=0.761). CONCLUSION: These findings suggest that the omission of subcuticular sutures during implantable venous port closure may not compromise peri-operative outcomes when OCA skin adhesives were used.

Outcome of neoadjuvant treatment for pancreatic cancer in elderly patients: comparative, observational cohort study.

BACKGROUND: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. METHODS: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared. RESULTS: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor. CONCLUSION: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.

In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids.

A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.

A risk prediction model for the development of subsequent primary melanoma in a population-based cohort.

BACKGROUND: Guidelines for follow-up of patients with melanoma are based on limited evidence. OBJECTIVES: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors. METHODS: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed. RESULTS: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score. CONCLUSIONS: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education.

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases.

Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.

Case series of testicular adrenal rest tumours in boys with congenital adrenal hyperplasia: A single centre experience.

Testicular adrenal rest tumours (TART) are aberrant adrenal tissue within the testes (1). Although benign, they can lead to obstruction of the seminiferous tubules and infertility in patients with congenital adrenal hyperplasia (CAH). We report six boys who developed TART, a complication of CAH. Diagnosis was confirmed by ultrasound and testicular vein sampling of elevated 17-hydroxyprogesterone (17-OHP) levels. Glucocorticoids dosages were increased 1½-2 folds to suppress size of the aberrant adrenal tissues. Despite reductions in 17-OHP, the lesions remained unchanged. Three patients had testis-sparing surgery to excise the TART and to preserve normal testicular tissues.

Sino-Nasal Outcome Test-22 quality-of-life patterns in patients presenting with nasal septal perforation.

OBJECTIVES: To assess the impact of nasal septal perforation (NSP) on quality of life. DESIGN: Retrospective cohort study. SETTING: Rhinology clinics from two hospitals in Liverpool, United Kingdom. PARTICIPANTS: Patients diagnosed with NSP. MAIN OUTCOME MEASURES: Patients (n = 26) diagnosed with NSP completed the Sino-Nasal Outcome Test-22 (SNOT-22). The collated data were compared with SNOT-22 scores from a cohort of healthy volunteers (n = 34) and a cohort of patients (n = 30) diagnosed with chronic rhinosinusitis (CRS). RESULTS: The mean total SNOT-22 score of NSP and CRS cohorts was higher than that observed in healthy volunteers. The mean total SNOT-22 score in the CRS cohort (57.2, standard deviation SD 10.3) was the higher than NSP (50.2, SD 23.5), although this difference did not achieve statistical significance. The mean score for the rhinologic-specific domains (rhinologic symptoms, extranasal rhinologic symptoms), ear/facial symptoms and psychological dysfunction domain was higher in the CRS cohort compared to NSP, although statistical significance was only observed in the extranasal rhinologic symptoms domain (11.2, SD 2.4 vs 6.4, SD 4.1). Conversely, the mean sleep dysfunction domain score for NSP (12.7, SD 7.5) was higher than CRS (10.0, SD 4.9, respectively) although this was not statistically significant. CONCLUSIONS: This study has assessed the clinimetric and psychometric properties of patients suffering from symptomatic NSP. Future reports should consider inclusion of SNOT-22 data but with the addition of perforation-specific symptoms (nasal crusting, epistaxis, whistling noise).

Assessing the ideal microwave duration for disinfection of sinus irrigation bottles-A quantitative study.

OBJECTIVES: Saline irrigation of the nasal cavity and paranasal sinuses has a recognised role in the management of chronic rhinosinusitis. However, bacterial recontamination of irrigation bottles through backflow from the sinonasal cavity is a concern in recurrent sinus cavity infections. While patients are encouraged to clean the irrigation bottles regularly, there remains significant concern that the use of contaminated bottles may perpetuate chronic rhinosinusitis. This study assesses the optimal microwave duration to achieve decontamination for each irrigation bottle component part (reservoir, tube and nozzle) using a standard, commercially available microwave. In addition, the irrigation fluid was also tested for contamination after each microwave cycle. STUDY DESIGN: Laboratory-based experimental study. PARTICIPANTS: No patients were involved in this study. MAIN OUTCOME MEASURES: The percentage in vitro decontamination of the bottles' components was determined following 30, 60, 90, 120, 150 seconds of microwave cycles. RESULTS: Complete decontamination of the bottles was not achieved at any of the tested microwave cycles. Levels of decontamination differed for the different bottle components, and the greatest degree of decontamination for all bottle components occurred at 90 seconds. Although higher levels of decontamination were observed at microwave durations exceeding 90 seconds, this was at the expense of thermal degradation and deformation of the reservoir plastic component of the irrigation bottle. Similarly, lowest contamination of irrigation fluid was observed at 120 seconds. CONCLUSIONS: This study highlights the importance of establishing precise decontamination procedures and recommends a microwave cycle of 90 seconds for optimal decontamination.

Phylogenetic analysis of Monascus and new species from honey, pollen and nests of stingless bees.

The genus Monascus was described by van Tieghem (1884) to accommodate M. ruber and M. mucoroides, two species with non-ostiolate ascomata. Species delimitation in the genus is still mainly based on phenotypic characters, and taxonomic studies that include sequence data are limited. The genus is of economic importance. Species are used in fermented Asian foods as food colourants (e.g. 'red rice' (ang-kak, angka)) and found as spoilage organisms, and recently Monascus was found to be essential in the lifecycle of stingless bees. In this study, a polyphasic approach was applied combining morphological characters, ITS, LSU, ß-tubulin, calmodulin and RNA polymerase II second largest subunit sequences and extrolite data, to delimit species and to study phylogenetic relationships in Monascus. Furthermore, 30 Monascus isolates from honey, pollen and nests of stingless bees in Brazil were included. Based on this polyphasic approach, the genus Monascus is resolved in nine species, including three new species associated with stingless bees (M. flavipigmentosus sp. nov., M. mellicola sp. nov., M. recifensis sp. nov., M. argentinensis, M. floridanus, M. lunisporas, M. pallens, M. purpureus, M. ruber), and split in two new sections (section Floridani sect. nov., section Rubri sect. nov.). Phylogenetic analysis showed that the xerophile Monascus eremophilus does not belong in Monascus and monophyly in Monascus is restored with the transfer of M. eremophilus to Penicillium (P. eremophilum comb. nov.). A list of accepted and excluded Monascus and Basipetospora species is given, together with information on (ex-)types cultures and barcode sequence data.

What is the publication rate for presentations given at the British Academic Conference in Otolaryngology (BACO)?

OBJECTIVES: The publication rate of some large academic meetings such as the American Academy of Otolaryngology-Head and Neck Surgery has been reported as 32%. We aimed to compare the rate of publication at the British Academic Conference in Otolaryngology (BACO) to allow surveillance of research activity in the United Kingdom (UK). DESIGN AND SETTING: The abstract records of both BACO 2009 and 2012 were examined. The MEDLINE database was searched using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and an iterative approach. We recorded time to publication as well as the authors' region and journal. MAIN OUTCOME MEASURES: publication rate by conference, region and journal. RESULTS: Twice the number of presentations were made at BACO 2012 (n = 814) compared to BACO 2009 (n = 387). Absolute numbers of publications were 158 in 2012 and 92 in 2009. Overall, the publication rate dropped from 24% overall in 2009 to 19% in 2012. This difference in proportions was not significant (P = 0.08). The number of abstracts accepted for BACO 2012 doubled from BACO 2009 in nearly every subspecialty category, except the general/training category, which trebled. For both conferences, head and neck was the largest subspecialty abstract category, as well as the largest subspecialty publication category. CONCLUSIONS: This study showed that the majority of abstracts presented at BACO 2009 and 2012 did not progress to publication. The rate of publication was similar to that seen in other general ENT meetings but do not compare favourably to the 69% rate seen for presentations made at the Otorhinolaryngological Research Society (ORS). The large increase in accepted abstracts at BACO 2012 may reflect growing competition for entry to specialist training.

An analysis of the fate of 917 manuscripts rejected from Clinical Otolaryngology.

OBJECTIVES: The fate of all manuscripts rejected from the journal Clinical Otolaryngology (CO) over a three-year period was investigated. The aim was to review publication rate, delay and the impact factors of the journals that the papers went on to be published in. DESIGN: In total, 917 papers were rejected from CO between 2011 and 2013. The fate of these manuscripts was determined by searching for the corresponding author's surname, and if necessary keywords from the manuscript title, in both PubMed and Google Scholar. MAIN OUTCOME MEASURES: The main outcome measures recorded were as follows: the subsequent publication of the article, delay to publication and journal of publication. RESULTS: In all, 511 papers were subsequently published in journals, representing 55.7% of all rejected manuscripts. The average delay was 15.1 months (standard deviation [sd] = 8.8). The impact factor of CO was found to be higher than the average of the journals that accepted the rejected manuscripts in all 3 years. Only 41 (8%) papers were published in journals with a higher impact factor than CO. Of all subsequently accepted manuscripts, 60 (11.7%) were found only on Google Scholar (and not on PubMed). CONCLUSIONS: Rejection from CO certainly does not prevent subsequent publication, although the papers tend to be published after a lengthy delay and in journals with a lower impact factor than CO. When performing literature searches, it is important to search more than one database to ensure as many of the relevant articles are found as possible.

A re-appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings.

OBJECTIVES: To review the rate of publication of papers in peer-reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979-1995). DESIGN: Literature review. SETTING: Merseyside ENT Research Collaborative. PARTICIPANTS: The abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations. MAIN OUTCOME MEASURES: Publication rates. RESULTS: A total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer-reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory-based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%). CONCLUSIONS: The publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high-impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and European journals.

Postoperative pain after laparoscopic cholecystectomy is not reduced by intraoperative analgesia guided by analgesia nociception index (ANI®) monitoring: a randomized clinical trial.

BACKGROUND: Laparoscopic cholecystectomy frequently results in significant immediate postoperative pain. A new pain monitor, analgesic nociception index (ANI®), based on heart rate variability, has recently been approved for intraoperative nociception monitoring. We designed a single-blind, parallel-group, randomized control trial to test the hypothesis that protocol-driven intraoperative analgesia guided by ANI during laparoscopic cholecystectomy would improve titration of intraoperative analgesics leading to decreased postoperative pain. METHODS: One hundred and twenty consecutive adult participants presenting for elective laparoscopic cholecystectomy were recruited. Participants were randomly allocated by sealed envelope to receive intraoperative morphine either guided by ANI via a protocol (intervention group) or guided by the anaesthetist with ANI concealed (control group). All participants received paracetamol, parecoxib, fentanyl at induction, and local anaesthetic to port sites. The primary endpoint was the presence of moderate/severe pain (visual analogue scale ≥50 mm) at any of the four time points in the first postoperative hour. Secondary endpoints included postoperative rescue morphine. RESULTS: Sixty participants were randomized to each group, and all but one drop-out from the intervention group were analysed. The usage of ANI guidance did not result in a decrease in the rate of moderate/severe pain (50.8% vs 45.0%: difference of -5.8%, 95% confidence interval, -23.7% to 12.1%, P=0.58), or the use of postoperative rescue analgesia. CONCLUSIONS: This randomized control trial of intraoperative ANI-guided morphine administration in elective laparoscopic cholecystectomy failed to show any advantage over the current standard of care, and demonstrated a high level of postoperative pain, despite the use of multimodal analgesia. CLINICAL TRIAL REGISTRATION: ANZCTR Reference ACTRN12612000953831 (URL: http://www.anzctr.org.au/trial_view.aspx?ID=362949).

Characterisation of patients with endoscopy-negative, computer tomography-negative midfacial segment pain using the sino-nasal outcome test.

BACKGROUND: The purpose of this study was to qualitatively characterise patients with midfacial segment pain (MSP) using the Sino-Nasal Outcome Test (SNOT). The data will provide a detailed overview of the physical and psychological impact on patients'well-being, and how it compares with the normal, healthy population. METHODS: Suitable patients were prospectively identified from the Multi-disciplinary Facial Pain Clinic at the Royal Liverpool University Hospital, based on the diagnostic criteria for MSP. The pre-treatment SNOT-22 of these patients were also compared to patients with chronic rhinosinusitis and normal healthy volunteers. RESULTS: Twenty-nine consecutive patients with a diagnosis of MSP were identified, and compared with 30 CRS patients and 34 healthy volunteers. The average SNOT-22 scores of MSP and CRS patients were higher than normal healthy volunteers. Patients with CRS had the highest rhinological subscale SNOT scores compared to normal healthy volunteers and MSP. Conversely, the reported ear and facial symptoms of MSP patients were most unfavourable. A similar trend was observed in reported sleep function where MSP patients recorded higher subscale scores than the other two cohorts. The subscale mean score for psychological function of MSP patients was not significant when compared to the mean score of patients diagnosed with CRS. CONCLUSION: MSP has an adverse impact on both physical and psychological well-being. The subtle differences in the SNOT subscores between MSP and CRS have provided greater insight into the character and disease impact of MSP. We propose that the SNOT may be suitably utilised in MSP to document disease severity and measure response to treatment.

Success and failure of dead-time models as applied to hybrid pixel detectors in high-flux applications.

The performance of a single-photon-counting hybrid pixel detector has been investigated at the Australian Synchrotron. Results are compared with the body of accepted analytical models previously validated with other detectors. Detector functionals are valuable for empirical calibration. It is shown that the matching of the detector dead-time with the temporal synchrotron source structure leads to substantial improvements in count rate and linearity of response. Standard implementations are linear up to ∼0.36 MHz pixel(-1); the optimized linearity in this configuration has an extended range up to ∼0.71 MHz pixel(-1); these are further correctable with a transfer function to ∼1.77 MHz pixel(-1). This new approach has wide application both in high-accuracy fundamental experiments and in standard crystallographic X-ray fluorescence and other X-ray measurements. The explicit use of data variance (rather than N(1/2) noise) and direct measures of goodness-of-fit (χ(r)(2)) are introduced, raising issues not encountered in previous literature for any detector, and suggesting that these inadequacies of models may apply to most detector types. Specifically, parametrization of models with non-physical values can lead to remarkable agreement for a range of count-rate, pulse-frequency and temporal structure. However, especially when the dead-time is near resonant with the temporal structure, limitations of these classical models become apparent. Further, a lack of agreement at extreme count rates was evident.

Nuclear and chloroplast DNA phylogeography reveals Pleistocene divergence and subsequent secondary contact of two genetic lineages of the tropical rainforest tree species Shorea leprosula (Dipterocarpaceae) in South-East Asia.

Tropical rainforests in South-East Asia have been affected by climatic fluctuations during past glacial eras. To examine how the accompanying changes in land areas and temperature have affected the genetic properties of rainforest trees in the region, we investigated the phylogeographic patterns of a widespread dipterocarp species, Shorea leprosula. Two types of DNA markers were used: expressed sequence tag-based simple sequence repeats and chloroplast DNA (cpDNA) sequence variations. Both sets of markers revealed clear genetic differentiation between populations in Borneo and those in the Malay Peninsula and Sumatra (Malay/Sumatra). However, in the south-western part of Borneo, genetic admixture of the lineages was observed in the two marker types. Coalescent simulation based on cpDNA sequence variation suggested that the two lineages arose 0.28-0.09 million years before present and that following their divergence migration from Malay/Sumatra to Borneo strongly exceeded migration in the opposite direction. We conclude that the genetic structure of S. leprosula was largely formed during the middle Pleistocene and was subsequently modified by eastward migration across the subaerially exposed Sunda Shelf.