Autumn fueling behavior in passerines in relation to migratory distance and daylength.

Songbirds have evolved diverse strategies to cope with seasonality, including long-, medium-, and short-distance migration. There is some evidence that birds with a longer migration distance deposit fuel faster. However, most studies focus on long-distance migrants. Comparisons between species with different migration distances are necessary to broaden our understanding of fueling capacity in migratory birds. We present maximum fuel deposition rates of five songbird species migrating along the southeast coast of Sweden in autumn with migration distances ranging from long (neotropical migrant) to short (partial/irruptive migrant) (Willow Warbler Phylloscopus trochilus, Lesser Whitethroat Curruca curruca, Common Chiffchaff P. collybita, European Robin Erithacus rubecula, and Blue Tit Cyanistes caeruleus). The birds were fed ad libitum in captivity and were exposed to either extended or natural daylength. All species ceased to increase in mass when they reached a certain fuel load, generally corresponding to migration distance, despite unlimited access to food and ample time for foraging. Blue Tits, Willow Warblers, and Lesser Whitethroats had the highest fuel deposition rates with extended daylength (19%, 20%, and 20%, respectively), and about 13% with natural daylength, which is comparable to the highest rates found in migratory songbirds in nature. European Robins and Common Chiffchaffs that winter in the temperate Mediterranean had the lowest fuel deposition rates (12% and 12% with extended daylength, respectively). Our results suggest that the long- and short-distance migrants in this study have developed an extreme capacity for rapid refueling for different reasons; speedy migration to distant wintering grounds or winter survival in Scandinavia. This study contributes to our current knowledge of maximum fuel deposition rates in different species and the limitations posed by daylength. We highlight the need for future studies of species with different migration strategies in order to draw broad conclusions about fueling strategies of migratory birds.

The Yellow-browed Warbler (Phylloscopus inornatus) as a model to understand vagrancy and its potential for the evolution of new migration routes.

Why and how new migration routes emerge remain fundamental questions in ecology, particularly in the context of current global changes. In its early stages, when few individuals are involved, the evolution of new migration routes can be easily confused with vagrancy, i.e. the occurrence of individuals outside their regular breeding, non-breeding or migratory distribution ranges. Yet, vagrancy can in theory generate new migration routes if vagrants survive, return to their breeding grounds and transfer their new migration route to their offspring, thus increasing a new migratory phenotype in the population. Here, we review the conceptual framework and empirical challenges of distinguishing regular migration from vagrancy in small obligate migratory passerines and explain how this can inform our understanding of migration evolution. For this purpose, we use the Yellow-browed Warbler (Phylloscopus inornatus) as a case study. This Siberian species normally winters in southern Asia and its recent increase in occurrence in Western Europe has become a prominent evolutionary puzzle. We first review and discuss available evidence suggesting that the species is still mostly a vagrant in Western Europe but might be establishing a new migration route initiated by vagrants. We then list possible empirical approaches to check if some individuals really undertake regular migratory movements between Western Europe and Siberia, which would make this species an ideal model for studying the links between vagrancy and the emergence of new migratory routes.

Customer perceptions of COVID-19 countermeasures on passenger ships during the pandemic.

The COVID-19 pandemic devastated substantial portions of the tourism industry; the cruise industry particularly suffered from negative publicity as the virus spread rapidly on cruise ships. The pandemic is a disaster that the industry has been forced to adapt to. This study illustrates, through a mixed-methods research design, what factors cruiseferry operators considered in their responses to the pandemic, whether the implemented countermeasures increased their customers' sense of security, and what countermeasures customers would agree to follow before boarding a ship. The study thereby provides insights into which countermeasures are likely to decrease customers' perceived health risks and which they are ready to accept or not on cruises during pandemics.

Is medical urgency of elderly patients with traumatic brain injury underestimated by emergency department triage?

Background: Mortality is high among elderly patients with traumatic brain injury (TBI). Recent data suggest that early surgical intervention and aggressive rehabilitation may reduce mortality rates even in elderly patients. Our aim was therefore to study the Rapid Emergency Triage and Treatment System-Adult (RETTS-A) triage of patients with isolated TBI and examine the differences in acute management according to age.Methods: We included 306 adult patients with isolated severe TBI and an abbreviated injury scale (AIS) score ≥3. Using a cut-off of 60 years of age, differences in triage priority according to RETTS-A, time to first computed tomography (CT) scan, length of hospital stay (LOS), and 30-day survival were studied.Results: In patients with an AIS score of 3 and 4, we observed that elderly patients had a longer time from admission to first CT scan. In addition, we observed that elderly patients were less often triaged with the highest priority level, despite similar AIS scores. LOS was significantly higher in elderly patients (median 9 days compared with 3 days for younger patients, p < 0.001). Finally, age, triage priority, and AIS score were independent risk factors for mortality.Conclusion: Elderly patients with isolated TBI are managed differently than younger patients, which could be due to an under-triage of elderly patients by RETTS-A.

[11C]Acetate positron emission tomography-computed tomography imaging of prostate cancer lymph-node metastases correlated with histopathological findings after extended lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the efficacy of combined [(11)C]acetate positron emission tomography and computed tomography ([(11)C]acetate-PET/CT) in regional lymph-node staging in patients with prostate cancer (PCa). MATERIAL AND METHODS: [(11)C]Acetate-PET/CT was performed in 19 PCa patients who subsequently underwent extended pelvic lymph-node dissection (ePLND). The [(11)C]acetate-PET/CT results were compared with the surgical and histopathological findings from 13 defined lymph-node regions. RESULTS: [(11)C]Acetate-PET/CT was true-positive for lymph-node metastases in nine patients, false-positive in three, false-negative in one patient and true-negative in six. The patient-by-patient-based sensitivity was 90% and the specificity 67%, the positive predictive value (PPV) was 75% and the negative predictive value (NPV) 86%. From a total of 114 nodal regions (mean 5.9 regions per patient), 484 lymph nodes (mean 25.5 nodes per patient) were removed and evaluated histopathologically. Forty-six lymph nodes from 24 out of 114 (21%) nodal regions were positive for PCa metastasis. The nodal-region-based sensitivity of [(11)C]acetate-PET/CT was 62%, specificity was 89%, PPV 62% and NPV 89%. CONCLUSION: [(11)C]Acetate-PET/CT detects PCa lymph-node metastases with high patient-by-patient-based sensitivity but low specificity, and low nodal-region-based sensitivity but high specificity. Its limited ability to detect microscopic lymph-node involvement makes ePLND essential in all patients diagnosed with positive nodes on [(11)C]acetate-PET/CT.

Atypical stromal hyperplasia of the prostate.

This paper reports a case of atypical stromal hyperplasia (ASH) of the prostate, i.e. a proliferation of stromal cells with scattered atypical nuclei, growing between benign prostatic glands. This is a rare lesion, but at least 36 cases have been reported. Although most ASHs arise in the transition zone in conjunction with benign prostatic hyperplasia, the current lesion was found in the peripheral zone of a 58-year-old man who underwent radical prostatectomy because of prostatic adenocarcinoma. The clinical impact of ASH is discussed and the literature reviewed.

Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005.

OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.

Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up.

To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levels < 2 microg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 microg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate.

Prevalence of prostate cancer at different levels of serum prostate-specific antigen (PSA) and different free: total PSA ratios in a consecutive series of men referred for prostate biopsies.

OBJECTIVE: In this retrospective study we report on the detection rate of prostate cancer (PCa) at different levels of prostate-specific antigen in serum (s-PSA) and at different PSA ratios (free:total PSA) during a 2-year period in patients without previously known PCa. MATERIAL AND METHODS: During the years 2001 and 2002, 361 consecutive patients were examined with ultrasound-guided core needle biopsies at our department. The patients were biopsied due to an increased s-PSA level, a low PSA ratio or findings at digital rectal examination (DRE). Patients with previously known cancer (T1a/b or cancer already detected with fine-needle aspiration cytology) were excluded. We used the BioPince biopsy needle, which has a stroke length of 32 mm. In 91% of the patients, eight biopsies were taken from the apex, mid-medial, mid-lateral and base positions bilaterally. RESULTS: Of the 361 patients, 188 (52%) had PCa. Most cancers were T1c or T2 tumors (51% and 34%, respectively). Among patients with an s-PSA level of < 4 ng/ml, 8/35 (23%) had PCa. Five of 13 patients with a normal DRE (T1c) and an s-PSA level of < 4 ng/ml had PCa. In total, in the PSA ratio intervals 0.05-0.1 and 0.11-0.17, cancer was found in 71% and 51% of cases, respectively. In contrast, only 35% of patients had positive biopsies when the PSA ratio was normal (p<0.01). CONCLUSIONS: The overall cancer detection rate was high and a large proportion of patients with an s-PSA level of < 4 ng/ml had PCa. The risk of having PCa increased considerably with a low PSA ratio.

Proteomics in prostate cancer research.

The incidence of early prostate cancer (PCa) among middle-aged men has increased rapidly. For many of these men, curatively intended treatment does more harm than good. Established prognostic factors are tumor stage and grade. As a result of earlier detection a majority of patients now have nonpalpable tumors (T1c) of intermediate grade (Gleason score 6). Prostate specific antigen in serum in such cases is generally at a low level and not a reliable predictor of prognosis. Altogether there is an urgent need for adjunctive prognostic indicators. In the search for relevant tumor markers for improved patient selection an exploration of the proteome (the human proteins) could be fruitful. This paper critically reviews the use of 2-dimensional gel electrophoresis (2-DE) for proteome research. Additional steps such as image analysis and mass spectrometry are described. Techniques based on non-2-DE platforms: surface-enhanced laser desorption/ionization (SELDI), isotope coded affinity tags (ICAT) and array-based technologies are also summarized. Although labor-intensive and time-consuming, 2-DE is presently the most powerful method for analysis of cellular protein phenotype and may potentially reveal gene regulations that cannot be detected on a genetic level.

Proteomics in clinical prostate research.

The incidence of early prostate cancer (PCa) has increased rapidly in recent years. The majority of newly diagnosed PCa are in early tumor phase. Presently, we do not have adequate biomarkers to assess tumor aggressiveness in individual cases. Consequently, too many patients are given curatively intended treatment. An exploration of the human proteome may provide clinically useful markers. 2-DE has been successfully used for analysis of the protein phenotype using clinical samples. Proteins are separated according to size and charge, gels are compared by image analysis, protein spots of interest are excised, and proteins identified by MS. This method is exploratory and allows protein identification. However, low-abundance proteins are difficult to detect and 2-DE is currently too labor-intensive for routine use. In recent years, nongel based techniques, such as LC-MS, SELDI-MS, and protein arrays have emerged. They require smaller sample sizes and can be more automated than 2-DE. In this review, we describe studies of the protein expression of benign prostatic tissue and PCa, which is likely to serve as the first step in prognostic biomarker discovery. The prostate proteome is still far from a complete mapping which would enhance our understanding of PCa biology.

CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients.

In this study, we investigated whether CD4+CD25high regulatory T cells (Treg) are increased in the tumor tissue and peripheral blood of early-stage prostate cancer patients undergoing prostatectomy. We show that the prevalence of CD4+CD25high T cells inside the prostate was significantly higher in the tumor compared with benign tissue from the same prostate. Furthermore, the frequency of CD4+CD25high T cells in peripheral blood was significantly higher in prostate cancer patients compared with normal donors. A proportion of the CD4+CD25high T cells was also shown to be glucocorticoid-induced TNF receptor, ICOS, and FOXP3 positive. Moreover, CD4+CD25+ T cells from blood and supernatants from cultured prostate tumor tissue samples exhibited immunosuppressive function in vitro. Furthermore, supernatants from cultured prostate tissue samples and prostate cancer ascites fluid induced migration of CD4+CD25+ T cells and were shown to contain the regulatory T cell chemokine CCL22 by ELISA. Our findings indicate that Tregs are an important cellular component of early-stage prostate tumors, and thus new therapeutic strategies aimed at inhibition or depletion of Tregs may improve prostate cancer immunotherapy.

Tissue shrinkage after fixation with formalin injection of prostatectomy specimens.

Prostate cancer volume correlates with stage, grade, and progression after prostatectomy. When tumor volume is measured planimetrically, results are multiplied by a correction factor to compensate for tissue shrinkage caused by processing. Injection of formalin into prostatectomy specimens was suggested for improved fixation. Our aim was to investigate how this affects the prostate volume. We studied 142 radical prostatectomy specimens. All prostates were immersed in 10% formalin. In 84 prostates (59%) we also injected 20 ml of formalin before routine fixation. The prostates were weighed unfixed after injection and after final fixation. The specimens were sliced and totally embedded. The transverse diameters of the prostates were measured on unfixed specimens and microscopic sections. The average weight loss after final fixation was 5.8 and 8.6% for formalin-injected specimens and standard-fixed specimens, respectively (p<0.001). However, when total shrinkage was estimated from the transverse diameters, there was no difference related to fixation technique (p=0.59). The average linear shrinkage was 4.5%, corresponding to a volume correction factor of 1.15. We conclude that formalin injection for fixation of prostate tissue does not influence tumor volume calculation compared to conventional fixation.

Correlation of protein expression, Gleason score and DNA ploidy in prostate cancer.

The prognosis of prostate cancer correlates with tumor differentiation. Gleason score and DNA ploidy are two prognostic factors that correlate with prognosis. We analyzed differences in protein expression in prostate cancer of high and low aggressiveness according to these measures. From 35 prostatectomy specimens, 29 cancer samples and 10 benign samples were harvested by scraping cells from cut surfaces. DNA ploidy was assessed by image cytometry. Protein preparations from cell suspensions were examined by 2-DE. Protein spots that differed quantitatively between sample groups were identified by MS fingerprinting of tryptic fragments and MS/MS sequence analysis. We found 39 protein spots with expression levels that were raised or lowered in correlation with Gleason score and/or DNA ploidy pattern (31 overexpressed in high-malignant cancer, 8 underexpressed). Of these, 30 were identified by MS. Among overexpressed proteins were heat-shock, structural and membrane proteins and enzymes involved in gene silencing, protein synthesis/degradation, mitochondrial protein import (metaxin 2), detoxification (GST-pi) and energy metabolism. Stroma-associated proteins were generally underexpressed. The protein expression of prostate cancer correlates with tumor differentiation. Potential prognostic markers may be found among proteins that are differentially expressed and the clinical value of these should be validated.

Evaluation of two sample preparation methods for prostate proteome analysis.

For laboratory techniques that require well-preserved proteins, such as 2-DE, fresh tissue must be harvested and processed as fast as possible to avoid proteolytic degradation. We describe a modified method for harvesting tissue from radical prostatectomy specimens for proteome analysis and compare it with the standard technique. Cells were scraped from cut surfaces of 11 prostate specimens. A fraction of the material was smeared on a glass slide and Giemsa stained for morphological control. The sample was collected in a medium with protease inhibitors, and the protein material was prepared for 2-DE. Filtering and Percoll centrifugation were omitted. Sample locations were noted on a specimen map. From the same area, a tissue block was harvested for comparison. The block was processed with the conventional technique including mechanical disintegration, filtering and Percoll centrifugation. Quality measures of 2-DE were similar with both methods. With the scrape sampling technique, control smears showed abundant epithelial cells and a cleaner background and processing was faster than with tissue block sampling. For proteomic analysis, the scrape sample technique has several advantages over the tissue block method.

Geographical variation in incidence of prostate cancer in Sweden.

OBJECTIVE: To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. MATERIAL AND METHODS: Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. RESULTS: The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. CONCLUSION: There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening.

The National Prostate Cancer Register in Sweden 1998-2002: trends in incidence, treatment and survival.

OBJECTIVES: To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. MATERIAL AND METHODS: Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35,223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. RESULTS: Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged < 70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA > 100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8-10) had a markedly reduced relative 5-year survival rate. CONCLUSIONS: It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Differential protein expression in anatomical zones of the prostate.

The prostate has three anatomical zones: the peripheral (PZ), the transition (TZ), and the central (CZ) zone. It is proposed that the CZ may be of mesodermal origin, whereas the other two are of endodermal origin. Proteome patterns in the zones were characterized to test for differences. Cells were scraped from macroscopically normal areas of PZ, TZ, and CZ in radical prostatectomy specimens. After exclusion of samples with cancer or prostatic intraepithelial neoplasia, 18 cases remained for analysis. Cells were collected in a medium with protease inhibitors, and the protein material was prepared for two-dimensional gel electrophoresis. The proteins in spots that differed quantitatively between regions were identified via mass spectrometric fingerprinting of tryptic fragments and selected tandem mass spectrometry sequence analysis. Ten proteins with significant zonal differential expression were identified, eight with underexpression in the CZ versus the PZ and the TZ (arginase II, ATP synthase, cytokeratin 8, lamin A/C, peroxiredoxin 4, protein disulfide isomerase A3, tropomyosin, and vimentin), and two with overexpression in the CZ (peroxiredoxin 2 and creatine kinase B). The PZ and TZ, although differing in terms of incidence of cancer and hyperplasia, have epithelium with highly similar major protein expression profiles. However, the protein profile of the CZ differs from that of the other regions, suggesting functional differences.