Longer Intervals Research Articles

Stereotactic radiotherapy for patients with bone metastases: a selected group with low rate of radiation treatment during the last month of life?

BackgroundComplex high-precision radiotherapy, such as stereotactic body radiotherapy (SBRT), should only be offered to patients with sufficiently long survival. In the context of bone metastases radiotherapy, low rates of treatment close to the end of life, e.g. last 30 days (RT30), may serve as a quality of care indicator. While traditional, pain-relieving short-course regimens have been studied comprehensively, real-world SBRT results are still limited.MethodsRetrospective analysis (2010–2023, n = 1117 episodes) of patients with bone metastases treated with traditional single-fraction (8 Gy × 1) or multi-fraction regimens (often 4 Gy × 5 or 3 Gy × 10) compared to stereotactic single-fraction (12–16 Gy × 1) or multi-fraction regimens.ResultsExcept for gender, almost all baseline variables were uneven distributed. Failure to complete fractionated radiotherapy was uncommon in the stereotactic (4%) and non-stereotactic group (3%), p = 1.0. With regard to RT30, relevant differences emerged (19% for 8-Gy single-fraction versus 0% for stereotactic single-fraction, p = 0.01). The corresponding figures were 11% for multi-fraction non-stereotactic and 2% for multi-fraction stereotactic, p = 0.08. Median overall survival was shortest after 8-Gy single-fraction irradiation (4.2 months) and longest after stereotactic multi-fraction treatment (13.9 months). Neither stereotactic radiotherapy nor multi-fraction treatment improved survival in multivariate Cox regression analysis. Factors significantly associated with longer survival included better performance status, lower LabBM score (5 standard blood test results), stable disease outside of irradiated area(s), metachronous distant metastases, longer time interval from metastatic disease to bone irradiation, and outpatient status.ConclusionThe implementation of SBRT for selected patients has resulted in low rates of non-completion and RT30. Optimal selection criteria remain to be determined, but in current clinical practice we exclude patients with poor performance status, unfavorable blood test results (high LabBM score) and progressive disease sites not amenable to SBRT. Established, guideline-endorsed short-course regimens, especially 8-Gy single-fraction treatment, continue to represent an important palliative approach.

Incidental findings of borderline ovarian tumor or ovarian cancer - real-world data on surgical and oncological outcomes.

Centralization of ovarian cancer treatment is associated with higher rates of optimal surgery and longer survival. However, preoperative diagnosis of ovarian cancer is challenging and some diagnoses are made incidentally after surgery. This study investigated the surgical and oncological outcomes of patients with incidental findings of borderline ovarian tumors or ovarian cancer who were centralized postoperatively and treated with a two-stage surgical procedure, and compared these with those of patients with adnexal masses of suspected malignancy who were offered a single-stage surgical procedure with intraoperative frozen section in a tertiary hospital. A database of 390 patients with adnexal masses and surgical treatment at the Bern University Hospital, Switzerland was retrospectively reviewed to identify patients with borderline ovarian tumors or ovarian cancer between 2010 and 2020. Among 390 patients with adnexal masses, 223 were diagnosed with a borderline ovarian tumor or ovarian cancer. Compared with patients with suspected malignancy and a centralized single-stage surgical procedure, patients with an incidental postoperative malignancy diagnosis and a two-stage surgical procedure underwent more surgical interventions (1.3 vs. 2.1 p<.001) and had a longer time interval from diagnosis to initiation of chemotherapy (33.3 vs. 45.1 p=.005) and to completion of surgical cytoreduction (31.9 vs. 73.7 days, p<.001). However, there were no differences in the rates of complete cytoreduction (90.0% vs. 93.2%, p=.719), intraoperative (11.3% vs. 13.7%, p=.664) or postoperative (38.7% vs. 37.0%, p=.884) complication rates, and number of hospitalization days (11.1 vs. 12.0 days, p=.369). An incidental diagnosis of malignancy with postoperative referral was neither associated with an increased risk of recurrence (hazard ratio (HR) 0.8, 95% confidence interval (CI) 0.6-1.8, p=.839) nor death (HR 0.7, 95% CI 0.4-1.1, p=.113), and there was no difference in mean recurrence-free survival between the study subgroups. Although patients with incidental findings of borderline ovarian tumors or ovarian cancer treated with a two-stage surgical procedure had a longer time to completion of surgical staging and initiation of chemotherapy, our results showed no negative impact on oncological outcomes.

Unlocking delays: revealing barriers to early diagnosis of childhood central nervous system tumors in an upper-middle-income country.

Childhood central nervous system (CNS) tumors tend to have a longer time interval until diagnosis than other pediatric malignancies. The aim is to describe the time to diagnosis among Brazilian pediatric patients treated at a tertiary center and explore associated factors. Cross-sectional study; application of questionnaires to parents of children with CNS tumors during outpatient visit or inpatient care. One hundred parents participated between August and November 2023. The median age of the children at diagnosis was 7.2years old. Low-grade glioma (LGG) was the most common tumor type (37%), followed by medulloblastoma (24%). The most frequent symptoms were morning and/or persistent vomiting and headache. The mean prediagnostic symptomatic interval (PSI) was 150days. The mean parental interval was shorter than the medical (58.1days vs 92.8days). LGGs and tumors located in the central area had longer intervals to diagnosis than other tumors (296 vs 54days) (p = 0.005) and (206 vs 155days) (p = 0.007), respectively. Despite 81% of the patients undergoing pediatric routine follow-up, 87% of them had been diagnosed at an emergency department. Children attended by the same physician had a shorter mean interval (18.2 vs 88.3days) than those assisted by different professionals (p = 0.015). The mean time for referral to our specialized center was 23days. This study is a crucial step in recognizing barriers to early diagnosis of CNS tumors in a middle-income country as low awareness of signs/symptoms by parents and health professionals, aiming to provide opportunities for intervention strategies to reduce the time to diagnosis.

Evidence at the landscape level links high predator/pest ratios to biocontrol services against aphids

Compared with external environment interferences, the interaction between arthropod natural enemies and pests is the key inherent driver determining the strength of biocontrol services. However, the extent to which this effect can suppress pests is still inconclusive. We combined two complementary experiments to determine how variation in an assemblage of generalist arthropod predators modified the level of biocontrol services for suppression of a key aphid pest in cotton fields. Using generalized linear mixed effect models (GLMM) and path analysis, we clarified the causal relationship between predator/aphid ratios (PAR) and (1) the resulting biocontrol services index (BSI) and (2) the aphid population growth index (APGI) as seen in field predator exclusion trials. We also measured the effect of PAR on APGI in more commercial cotton fields. Our results, at landscape level, indicate that when PAR values increased one unit, BSI values improved 34.1 %, and reduced aphid population growth 28.3 % (the standardized effect coefficient in path analysis) during two weeks in field cage-exclusion trials. The effect of high predator/aphid ratios on reducing the aphid population growth rates was also significant in more commercial cotton fields, which were sampled over a longer time interval (4 weeks). Our study confirmed that there was a causal relationship between the natural enemy/pest ratio and the level of biological pest control services for predators and aphid population growth in crop fields. PAR values (predator/aphid ratios) can, therefore, be used to predict the level of biocontrol services in this context instead of relying on more labor-intensive cage exclusion studies.

Floristic changes following the chestnut blight may be delayed for decades.

A survey conducted in the 1920s, prior to the chestnut blight, indicated that chestnuts and oaks were codominant canopy species in White Oak Canyon, Shenandoah National Park, Virginia. A second survey in 1977 suggested that chestnuts were being replaced by tree species present before the blight, particularly oaks. In 2021, we resurveyed the 10 sites included in our 1977 survey and also recorded canopy and understory trees that grew above remnant chestnut sprouts. The canopy changed more substantially during the second interval (since 1977). Birch and maples were now more abundant. Hemlock declined, and oaks were less common in the canopy. In general, the trees considered as early to mid-successional have replaced oaks and hemlock. Chestnut sprouts have become much less common since 1977, presumably as repeated cycles of diebacks have weakened rootstocks. Those sites where chestnut sprouts have persisted until 2021 differed from neighboring sites without them. Chestnut sprouts were rare in sites with birch and hemlock; chestnut has persisted in locations with red oaks in the canopy and with few other understory competitors. This survey has been conducted over a longer time interval than previous studies that asked similar questions and our results suggest that changes to the forest composition following the loss of the American chestnut may be greater than previously recognized although the relative contribution of losing this codominant species is unclear.

Phenology Across Scales: An Intercontinental Analysis of Leaf‐Out Dates in Temperate Deciduous Tree Communities

ABSTRACTAimTo quantify the intra‐community variability of leaf‐out (ICVLo) among dominant trees in temperate deciduous forests, assess its links with specific and phylogenetic diversity, identify its environmental drivers and deduce its ecological consequences with regard to radiation received and exposure to late frost.LocationEastern North America (ENA) and Europe (EUR).Time Period2009–2022.Major Taxa StudiedTemperate deciduous forest trees.MethodsWe developed an approach to quantify ICVLo through the analysis of RGB images taken from phenological cameras. We related ICVLo to species richness, phylogenetic diversity and environmental conditions. We quantified the intra‐community variability of the amount of radiation received and of exposure to late frost.ResultsLeaf‐out occurred over a longer time interval in ENA than in EUR. The sensitivity of leaf‐out to temperature was identical in both regions (−3.4 days per °C). The distributions of ICVLo were similar in EUR and ENA forests, despite the latter being more species‐rich and phylogenetically diverse. In both regions, cooler conditions and an earlier occurrence of leaf‐out resulted in higher ICVLo. ICVLo resulted in ca. 8% difference of radiation received from leaf‐out to September among individual trees. Forest communities in ENA had shorter safety margins as regards the exposure to late frosts, and were actually more frequently exposed to late frosts.Main ConclusionsWe conducted the first intercontinental analysis of the variability of leaf‐out at the scale of tree communities. North American and European forests showed similar ICVLo, in spite of their differences in terms of species richness and phylogenetic diversity, highlighting the relevance of environmental controls on ICVLo. We quantified two ecological implications of ICVLo (difference in terms of radiation received and exposure to late frost), which should be explored in the context of ongoing climate change, which affects trees differently according to their phenological niche.

Immunotherapy at the end of life.

188 Background: It is well established in the literature that cancer treatment administered at the end of life (EOL) does not improve either quality of life or survival rates. Patients undergoing systemic cancer treatments at near the EOL often have reduced access to hospice services and an increased likelihood of acute medical interventions, including emergency department visits, intensive care unit admissions, and in-hospital deaths. The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer care over the past decade, demonstrating the ability to extend progression-free survival and overall survival in patients with various cancers. Furthermore, ICIs may represent a promising therapeutic option for adults with impaired performance status (PS) due to their relatively favorable side-effect profile when compared to conventional chemotherapy. While numerous studies have examined chemotherapy at the end of life, research specifically focusing on the administration of immunotherapy during this period is scarce. Methods: We conducted a retrospective chart review using the electronic medical record database at Scripps clinic focusing on cancer patients undergoing immunotherapy who passed away between June 1, 2017, and August 30, 2023, comprising a cohort of 641 individuals. Our investigation was designed to provide a retrospective overview of patient characteristics and outcomes, with a specific emphasis on factors at EOL. Results: The most prevalent tumor types were lung (34%), GI (21%), skin (13%), GU (12.6%) and others (19.4%). On average, no patients received immunotherapy in the last 30 days of their lives. Among the different cancer types, breast cancer patients had the longest interval between last treatment and death, averaging 259 days. This was followed by patients with head and neck cancer (207 days), skin cancer (199 days), genitourinary (GU) cancers (177 days), lung cancer (140 days), gynecological (GYN) cancers (135 days), and gastrointestinal (GI) cancers (134 days). 19 patients died from immune-related adverse events (IrAEs). These patients had the shortest interval between their last treatment and death, with a mean of 34 days. This was followed by those who died due to cancer progression, with an average interval of 148 days. Conclusions: The decision to administer anticancer therapies near the EOL is increasingly complex. Oncologists must carefully discuss immunotherapy with patients, monitor for IrAEs, and consider discontinuing treatment if there is disease progression, worsening PS or after two years of treatment.

Socio-demographic predictors of the time interval between successive hospitalizations among patients with borderline personality disorder

Background: Borderline personality disorder (BPD) affects 0.7 to 2.7% of the adult population and higher rates are reported in inpatient care. Hospitalizations of BPD patients are a complex and controversial challenge for mental health professionals. Recurrent hospitalizations are common and it is essential to identify risk factors that characterize patients who benefit from their hospitalization and those who return to the ward shortly after discharge. Aim: To investigate the potential link between BPD patients’ socio-demographic factors and the expected time interval between their successive hospitalizations. Methods: A retrospective analysis of 1051 hospitalization records from 174 BPD patients. Through univariate, bivariate, and multivariate analyses, we investigated the possible relationship between patients’ primary socio-demographic factors and the time between their successive hospitalizations. Results: Patients’ age, marital status, and living arrangement were found to be statistically connected with the time interval between successive hospitalizations. Specifically, being older, married and/or patients to live with one’s spouse/partner seem to be linked with a longer time interval between successive hospitalizations compared to patients who are young, single/divorced and/or those who live with their parents. Conclusions: The expected time interval between successive hospitalization of BPD patients can be partly explained by their socio-demographic characteristics.

The performance of alternative GPS tracking devices: a case report on wild boars (Sus scrofa)

BackgroundTelemetry studies on terrestrial mammals have been carried out almost exclusively using neck collar-mounted devices. However, collars are not suitable for all species and all age classes and may therefore compromise animal welfare and data quality requirements. Here, we evaluate the use of non-collar tracking devices on wild boars (Sus scrofa), a species for which collars may be problematic due to neck shape and seasonal body mass variation. We tested pelt-glued tags and three types of GPS ear tags. In addition, animals were marked with plain cattle ear tags.ResultsThe tested GPS tags exhibited various technical challenges related mostly to satellite coverage of the study area and tag loss. However, GPS devices enabled moderate movement monitoring of weeks to months, whereas plain cattle ear tags offered information on displacement over longer time intervals. The longest direct dispersal distance (163 km) by a wild boar sounder was discovered by cattle tags.ConclusionsData volume and quality obtained from small tags are inferior to data provided by GPS collars, but low-fix rate tags may enable monitoring of individuals with reduced invasiveness. Moreover, these tags enable tracking in cases where the collar is not an option. The low price and small size of the devices together with technical developments may offer cost-effective tools for future studies on dispersal and survival.

Schwabe Solar Cycle in 1000–1700: Variations in the Length and Amplitude

One of the most significant features of solar activity is its variability over a wide range of periods, with the dominance of the 11-year cycle or the Schwabe cycle. In this work, a wavelet analysis of data on solar activity in 1000–1700 was carried out, obtained using the number of auroras, taking into account the contribution of the geomagnetic field. The obtained results demonstrate the stable presence of an 11-year cycle during the entire time interval of 1000–1700 A. D. It was found that in 1000–1350 there was a systematic increase in the length of the Schwabe cycle, after which its decline was traced. At the same time, the length of the solar cycle increases during the grand minima of Oort (13 years), Wolf (14 years) and Spörer (14–15 years). It was found that the correlation between the amplitude and the length of the solar cycle was maintained throughout the entire period of time 1000–1700, but its sign changed. In addition, it was obtained that the correlation between the amplitude of the cycle and the length of the previous cycle is stronger than the correlation between the amplitude and length of the same cycle. This result is similar to that previously known for instrumental series. However, we have shown that this pattern persists over a much longer time interval, and it does not depend on the sign of the correlation. The paper also provides indications of the existence of a variation with a period of 30–40 years in solar activity in 1000–1550.

Evolution of Characteristics of Vertical Electric Current and Magnetic Field in Active Regions of the Sun and their Relation to Powerful Flares

The study of evolution of magnetic field and electric currents in active regions of the Sun over a long-time interval is of interest for understanding the processes of accumulation and release of energy in them, leading to various phenomena that affect space weather. In this work, based on the photospheric vector magnetograms of the Helioseismic and Magnetic Imager instrument aboard the Solar Dynamics Observatory, an analysis was made of the evolution of a number of characteristics of the magnetic field and vertical electric current in three active regions 11158, 11675, and 12673 that produced class M and X flares, during the time from their origin in the Eastern hemisphere, during the passage through the solar disk, and until the disappearance near the Western limb with a step of 2 hours. The characteristics under consideration included: the power-law exponent of the probability density function of the absolute value of the vertical electric current density, the maximum of the absolute value of the vertical current density, the signed and unsigned total vertical currents and the unsigned total vertical and horizontal magnetic fluxes, the energy of the nonlinear force-free and potential magnetic fields, the free magnetic energy, and the number of islands with strong vertical current. Some regularities in the behaviour of the characteristics under consideration are found, in particular regarding the occurrence of solar flares. The correlation coefficients between pairs of these characteristics are calculated. Additionally, M. Aschwanden’s approach is shown to be promising for predicting the maximum X-ray class of a flare based on the calculation of the energy of the potential magnetic field in active regions. The results obtained can be used to predict powerful solar flares.

2287 Residents with dementia had an increase in BMI after the introduction of an extra meal in nursing homes in Norway

Abstract Introduction The past decade, many nursing homes in Norway have introduced an extra meal daily, with a hot lunch, and pushing dinner to later in the day. This initiative aims to reduce the long-time interval between breakfast and supper. This study examines how an extra meal affects the residents’ body mass index (BMI) at nursing homes in Norway. Research questions include how an extra meal affects BMI among residents in the dementia unit. Method We used a cross-sectional design to analyse data from residents over 65 years old in dementia care units. Both parametric and non-parametric statistical tests were used to evaluate changes in BMI. Results The results of the study show that the dementia unit experienced an increase in BMI following the introduction of an extra meal. At most, we saw a weight gain of up to 7 kg over two years among residents. Our study reveals that the introduction of an extra meal resulted in a slight increase in BMI among the residents with dementia, which does not correspond with previous studies indicating malnutrition among these residents. The dementia disease reduces functional abilities, and challenges related to mealtime behaviour, restlessness, and depression can lead to weight loss. The fact that our results show a slight increase in BMI at the dementia units may be related to these residents often being troubled with restlessness and not finding the peace to consume a full meal. By introducing an extra meal, the total food intake increases since residents still eat a little at each meal, and focusing more on accommodating each resident might have influenced the increase in BMI values. Conclusion The study indicates that the introduction of an extra meal has a positive effect on the BMI value of residents with dementia in nursing homes.

Optimizing tracking and completion of follow-up colonoscopy after abnormal stool tests at health systems participating in the Centers for Disease Control and Prevention's Colorectal Cancer Control Program.

We present findings from an assessment of award recipients' partners from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP). We describe partners' processes of identifying and tracking patients undergoing stool-based screening. We analyzed data from eight CRCCP award recipients purposively sampled and their partner health systems from 2019 to 2023. The data included number of stool-based tests distributed and returned; abnormal findings; referrals and completion of follow-up colonoscopies; and colonoscopy findings. We also report on strategies to improve tracking of stool-based tests and facilitation of follow-up colonoscopies. Five of eight CRCCP award recipients reported that all or some partner health systems were able to report stool test return rates. Six had health systems that were able to report abnormal stool test findings. Two reported that health systems could track time to follow-up colonoscopy completion from date of referral, while four could report colonoscopy completion but not the timeframe. Follow-up colonoscopy completion varied substantially from 24.2 to 75.5% (average of 47.9%). Strategies to improve identifying and tracking screening focused mainly on the use of electronic medical records; strategies to facilitate follow-up colonoscopy were multi-level. Health systems vary in their ability to track steps in the stool-based screening process and few health systems can track time to completion of follow-up colonoscopy. Longer time intervals can result in more advanced disease. CRCCP-associated health systems participating in this study could support the implementation of multicomponent strategies at the individual, provider, and health system levels to improve tracking and completion of follow-up colonoscopy.

Revisiting the Spatial Cycle: Intra-Regional Development Patterns and Future Population Dynamics in Metropolitan Athens, Greece

Being intertwined with economic development, urbanization determines the present and future development path of regions and countries. The intimate relationship between urban expansion and economic development is of particular interest in the case of large regions with complex (and mostly non-linear) socio-demographic dynamics and a relevant primacy in the metropolitan system of a given country. Typical examples of advanced economies with settlement systems characterized by a high degree of city primacy are peripheral and disadvantaged European countries such as Portugal and Greece. For instance, the administrative region of Attica—centered on Athens, the Greek capital city—represents the largest metropolitan area of the country, hosting almost 3.8 million inhabitants in 2021 (36.2% of the Greek population). In this context, this study investigates the internal redistribution of the resident population in metropolitan Athens and the progressive development of satellite cities over a relatively longtime interval, testing the assumptions of the Spatial Cycle Theory (SCT) between 1951 and 2021 and predicting future development paths up to 2051. To investigate past, present, and future intra-regional population trends, we used data released from decadal (1951–2021) censuses and demographic forecasts for the years 2031, 2041, and 2051. Being in line with the SCT, the empirical results of our study document how demographic dynamics of individual centers influence largely—and independently—the long-term development of metropolitan regions, both with policy/planning regulation and in conditions of non-intervention (spontaneous urban growth).

SARS-CoV-2 reinfection rate before and after VOC Omicron emergence: a retrospective study in Brazil.

SARS-COV-2 reinfection has been reported worldwide, although its rate remains unclear. VOC Omicron's emergence and its sub-variants led to an unprecedented number of COVID-19 cases in several countries, raising concerns regarding reinfection rates. 324,979 RT-qPCR-confirmed positive cases (72.57% from Minas Gerais State) diagnosed between April 1, 2020, and August 31, 2022, at the Hermes Pardini, Grupo Fleury (Brazil) were used to estimate the reinfection rate. Instances of reinfection were characterized by two positive tests occurring with a minimum interval of 60 days. We identified 11,669 cases of reinfection. The states of Minas Gerais, São Paulo, Rio de Janeiro and Goiás represented almost 41% of the reinfections. Up until epidemiological week 46 of 2020, only 14 cases of reinfection were recorded. The majority of reinfections, totalling 6,316 cases, were detected during the circulation period of the Omicron and its sublineages BA.1 and BA.2. Another 4,273 reinfections occurred during the circulation period of sublineages BA.4 and BA.5, revealing two distinct groups of observations. The first group comprised cases of reinfection with a shorter time interval (two infections within a period of up to 200 days), while the second group was associated with a longer time interval (two infections within a period of more than 500 days). The reinfection rate during this period was nearly 8%, which is six times higher than the rate observed at the beginning of the study. In conclusion, our study underscores the dynamic nature of SARS-CoV-2 reinfections and their correlation with emerging variants such as Omicron.

Coping with stress: Salt type, concentration, and exposure history limit life history tradeoffs in response to road salt salinization

Substantial increases in the salinity of freshwater ecosystems has occurred around the globe from causes such as climate change, industrial operations, and the application of road deicing salts. We know very little about how plastic responses in life history traits or rapid evolution of new traits among freshwater organisms could promote stability in ecological communities affected by salinization. We performed a cohort life history analysis from birth to death with 180 individuals of a ubiquitous freshwater zooplankter to understand how life history traits are affected by exposure to two common salt types causing salinization—sodium chloride (NaCl) and calcium chloride (CaCl2)—across two environmentally relevant concentrations. We also tested if a multi-generational exposure history to high salinity altered life-history responses. We tracked and measured lifespan, time to maturation, brood size, brood interval, and body size. We found smaller brood sizes but slightly longer lifespans occurred at a low concentration of NaCl (230 mg Cl−/L). The longer lifespans led to more, albeit smaller broods, which generated a similar lifetime reproductive output compared to the no-salt control populations. At higher concentrations of NaCl and CaCl2, we found lifetime reproductive output was reduced by 23 % to 83 % relative to control populations because no tradeoff among life history traits occurred. In CaCl2, we observed shorter life spans, longer time intervals between smaller broods, and smaller body sizes leading to reduced lifetime reproductive output. We also found that a multi-generational exposure to the salt types did not convey any advantages for lifetime reproductive output. In some cases, the exposure history worsened the life history trait responses suggesting maladaptation. Our findings suggest that life history tradeoffs for freshwater species can occur in response to salinization, but these tradeoffs will largely depend on salt type and concentration, which will have implications for biodiversity and ecological stability.

Influence of Tumor Characteristics and Time to Metastatic Disease on Oncological Outcomes in Metachronous Metastatic Prostate Cancer Patients

IntroductionMetachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset. Patients and MethodsWe relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa. ResultsOf 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS. ConclusionTiming of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa.

Assessing The Toxicity Of Heavy Metals And Potential Tolerance Of Common Bean (Phaseolus vulgaris) While Monitoring The Population Dynamics Of The Associated Rhizobia

Microbially-assisted phytoremediation (MAP) is increasingly recognized as the feasible alternative for removing hazardous heavy metals (HMs) from contaminated environments. However, the dynamics of rhizobial-plant interactions during phytoremediation remain unclear. This study investigated the toxicity of some selected heavy metals (Cobalt, Nickel, and Manganese), the potential tolerance of Phaseolus vulgaris grown in the HMs-rich effluents, and the population dynamics of the associated Rhizobia within the Katsina metropolis. After 80 samples of P. vulgaris collected from Lambun Sarki garden were exposed to 10 mL of 0.5-2g/L of Ni and Co and 5-20 g/L Mn, respectively, in mesocosms, and the plants treated with 10 mL HMs solutions daily, for three weeks. Indices of HMs toxicity on seeds and plants (4 and 3, respectively) were monitored in all treatments. Weekly rhizobial counts on Congo Red Yeast Extract Mannitol Agar (CRYEMA) were taken to monitor rhizobial population dynamics. Pure isolates obtained after three iterations were identified biochemically. One-way ANOVA was employed for statistical analyses using AnalyStat (version 1.6.50). Generally, Ni exerts the highest toxicity, with Mn having less toxicity. Average rhizobial counts increased weekly, with high counts obtained in Ni and Mn treatments. However, they did not differ significantly between weeks (p = 0.061). Thus, longer time intervals (&gt;2 weeks) are required to observe significant shifts in population dynamics. Moreover, HMs concentration did not affect the colony counts (p = 1.00). Metabolism profile of the preliminarily identified Rhizobium sp. and Sinorrhizobium melliloti evidenced HMs removal and plant growth promotion ability. The research demonstrated the phytoremediation ability of P. vulgaris and how rhizospheric population dynamics change during phytoremediation and contributed towards understanding HMs impact as environmental stressors on rhizospheric plant-microbe interactions. Future research targeting the hyperaccumulation capacity of the plants and heavy metals tolerance of the identified rhizobia are recommended, as this may help in knowing the BCF, TF, and BAC of the plants as well as the tolerable amount of the heavy metals to the bacteria

Antimicrobial assay and controlled drug release studies with novel eugenol imprinted p(HEMA)-bacterial cellulose nanocomposite, designed for biomedical applications

In this study, a novel bio-composite material that allow sustained release of plant derived antimicrobial compound was developed for the biomedical applications to prevent the infections caused by microorganisms resistant to commercial antimicrobials agents. With this aim, bacterial cellulose (BC)-p(HEMA) nanocomposite film that imprinted with eugenol (EU) via metal chelated monomer, MAH was prepared. Firstly, characterization studies were utilized by FTIR, SEM and BET analysis. Then antimicrobial assays, drug release studies and in vitro cytotoxicity test were performed. A significant antimicrobial effect against both Gram (+) Staphylococcus aureus and Gram (-) Escherichia coli bacteria and a yeast Candida albicans were observed even in low exposure time periods. When antimicrobial effect of EU compared with commercially used agents, both antifungal and antibacterial activity of EU were found to be higher. Then, sustained drug release studies showed that approximately 55% of EU was released up to 50 h. This result proved the achievement of the molecular imprinting for an immobilization of molecules that desired to release on an area in a long-time interval. Finally, the in vitro cytotoxicity experiment performed with the mouse L929 cell line determined that the synthesized EU-imprinted BC nanocomposite was biocompatible.

Three modes of evolution?Remarks on rates of evolution and time scaling.

Rates of evolution get smaller when they are measured over longer time intervals. As first shown by Gingerich, rates of morphological change measured from fossil time series show a robust minus-one scaling with time span, implying that evolutionary changes are just as large when measured over a hundred years as when measured over a hundred-thousand years. On even longer time scales, however, the scaling shifts toward a minus-half exponent consistent with evolution behaving as Brownian motion, as commonly observed in phylogenetic comparative studies. Here, I discuss how such scaling patterns arise, and I derive the patterns expected from standard stochastic models of evolution. I argue that observed shifts cannot be easily explained by simple univariate models, but require shifts in mode of evolution as time scale is changing. To illustrate this idea, I present a hypothesis about three distinct, but connected, modes of evolution. I analyze the scaling patterns predicted from this, and use the results to discuss how rates of evolution should be measured and interpreted. I argue that distinct modes of evolution at different time scales act to decouple micro- and macroevolution, and criticize various attempts at extrapolating from one to the other.