Validity of the modified Rankin Scale in patients with aneurysmal subarachnoid hemorrhage: a randomized study.

PURPOSE: The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs). METHODS: This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses. RESULTS: In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = - 0.546, while with RAND-36 physical and mental component scores the correlation was r = - 0.439and r = - 0.574 respectively, and with SS-QoL it was r = - 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was - 0.08 (SD 0.915). None of the hypotheses for responsiveness were met. CONCLUSION: The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints. REGISTRATION: URL: https://trialsearch.who.int ; Unique identifier: NL7859, Date of first administration: 08-07-2019.

The effect of smell training on COVID-19 induced smell loss.

OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.

A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Review of technologies for biomethane production and assessment of Eu transport share in 2030.

The upgrade to biomethane allows extending biogas applications to transport sectors, supporting EU goals toward carbon neutrality. Biomethane produced from biogas upgrading can today rely on a large number of plants, estimated by the European Biogas Association in over 17000 in 2016, for a total installed capacity of 9985 GW (EBA, 2017). After 2020, biogas and biomethane will count towards the 32% target of renewable energy share of the EU energy consumption, and towards a sub-target of minimum 14% of the energy consumed in the transport sector by 2030 (REDII). In this framework, the paper aims to define the current market penetration of biogas upgrading technologies. A database has been created for EU-28, to highlight the relative importance of each technology. Based on the database, a EU production potential is defined, along with the EU demand potential for transport, in order to verify the match between supply and demand. The analysis of the current state of play of the sector suggests that a large potential can be foreseen for near future; the expected increase in biomethane production is based also on the possibility to convert residual feedstocks, such as Municipal Solid Wastes. In this work a moderate technology penetration scenario has been set for EU-28, reaching a potential for biomethane of 18 billion m3/year in 2030. A large share of this potential can be devoted to transport, with a relevant impact on the sector. LNG appears suitable for pushing the market uptake of biomethane in the transport sector. Among the potential uses of biomethane for transport, it is worth considering that the natural gas use in the maritime and internal waterways sectors is getting momentum. The current analysis aimed to highlight the potential of renewable energy-based alternatives to natural gas. Eventually, it is worth noticing that the real market deployment of this potential will be determined by the energy market conditions, and by the member states capability to stimulate the industry through a coherent set of supporting initiatives.

Fluctuating selection and its (elusive) evolutionary consequences in a wild rodent population.

Temporal fluctuations in the strength and direction of selection are often proposed as a mechanism that slows down evolution, both over geological and contemporary timescales. Both the prevalence of fluctuating selection and its relevance for evolutionary dynamics remain poorly understood however, especially on contemporary timescales: unbiased empirical estimates of variation in selection are scarce, and the question of how much of the variation in selection translates into variation in genetic change has largely been ignored. Using long-term individual-based data for a wild rodent population, we quantify the magnitude of fluctuating selection on body size. Subsequently, we estimate the evolutionary dynamics of size and test for a link between fluctuating selection and evolution. We show that, over the past 11 years, phenotypic selection on body size has fluctuated significantly. However, the strength and direction of genetic change have remained largely constant over the study period; that is, the rate of genetic change was similar in years where selection favoured heavier vs. lighter individuals. This result suggests that over shorter timescales, fluctuating selection does not necessarily translate into fluctuating evolution. Importantly however, individual-based simulations show that the correlation between fluctuating selection and fluctuating evolution can be obscured by the effect of drift, and that substantially more data are required for a precise and accurate estimate of this correlation. We identify new challenges in measuring the coupling between selection and evolution, and provide methods and guidelines to overcome them.

Phenotype-associated inbreeding biases estimates of inbreeding depression in a wild bird population.

Inbreeding depression is usually quantified by regressing individual phenotypic values on inbreeding coefficients, implicitly assuming there is no correlation between an individual's phenotype and the kinship coefficient to its mate. If such an association between parental phenotype and parental kinship exists, and if the trait of interest is heritable, estimates of inbreeding depression can be biased. Here we first derive the expected bias as a function of the covariance between mean parental breeding value and parental kinship. Subsequently, we use simulated data to confirm the existence of this bias, and show that it can be accounted for in a quantitative genetic animal model. Finally, we use long-term individual-based data for white-throated dippers (Cinclus cinclus), a bird species in which inbreeding is relatively common, to obtain an empirical estimate of this bias. We show that during part of the study period, parents of inbred birds had shorter wings than those of outbred birds, and as wing length is heritable, inbred individuals were smaller, independent of any inbreeding effects. This resulted in the overestimation of inbreeding effects. Similarly, during a period when parents of inbred birds had longer wings, we found that inbreeding effects were underestimated. We discuss how such associations may have arisen in this system, and why they are likely to occur in others, too. Overall, we demonstrate how less biased estimates of inbreeding depression can be obtained within a quantitative genetic framework, and suggest that inbreeding and additive genetic effects should be accounted for simultaneously whenever possible.

Genetic variance components and heritability of multiallelic heterozygosity under inbreeding.

The maintenance of genetic diversity in fitness-related traits remains a central topic in evolutionary biology, for example, in the context of sexual selection for genetic benefits. Among the solutions that have been proposed is directional sexual selection for heterozygosity. The importance of such selection is highly debated. However, a critical evaluation requires knowledge of the heritability of heterozygosity, a quantity that is rarely estimated in this context, and often assumed to be zero. This is at least partly the result of the lack of a general framework that allows for its quantitative prediction in small and inbred populations, which are the focus of most empirical studies. Moreover, while current predictors are applicable only to biallelic loci, fitness-relevant loci are often multiallelic, as are the neutral markers typically used to estimate genome-wide heterozygosity. To this end, we first review previous, but little-known, work showing that under most circumstances, heterozygosity at biallelic loci and in the absence of inbreeding is heritable. We then derive the heritability of heterozygosity and the underlying variances for multiple alleles and any inbreeding level. We also show that heterozygosity at multiallelic loci can be highly heritable when allele frequencies are unequal, and that this heritability is reduced by inbreeding. Our quantitative genetic framework can provide new insights into the evolutionary dynamics of heterozygosity in inbred and outbred populations.

Predicting Cognitive Functioning for Patients with a High-Grade Glioma: Evaluating Different Representations of Tumor Location in a Common Space.

Cognitive functioning is increasingly considered when making treatment decisions for patients with a brain tumor in view of a personalized onco-functional balance. Ideally, one can predict cognitive functioning of individual patients to make treatment decisions considering this balance. To make accurate predictions, an informative representation of tumor location is pivotal, yet comparisons of representations are lacking. Therefore, this study compares brain atlases and principal component analysis (PCA) to represent voxel-wise tumor location. Pre-operative cognitive functioning was predicted for 246 patients with a high-grade glioma across eight cognitive tests while using different representations of voxel-wise tumor location as predictors. Voxel-wise tumor location was represented using 13 different frequently-used population average atlases, 13 randomly generated atlases, and 13 representations based on PCA. ElasticNet predictions were compared between representations and against a model solely using tumor volume. Preoperative cognitive functioning could only partly be predicted from tumor location. Performances of different representations were largely similar. Population average atlases did not result in better predictions compared to random atlases. PCA-based representation did not clearly outperform other representations, although summary metrics indicated that PCA-based representations performed somewhat better in our sample. Representations with more regions or components resulted in less accurate predictions. Population average atlases possibly cannot distinguish between functionally distinct areas when applied to patients with a glioma. This stresses the need to develop and validate methods for individual parcellations in the presence of lesions. Future studies may test if the observed small advantage of PCA-based representations generalizes to other data.

Cost-effectiveness of radioguided occult lesion localization (ROLL) versus wire-guided localization (WGL) in breast conserving surgery for nonpalpable breast cancer: results from a randomized controlled multicenter trial.

BACKGROUND: Accurate preoperative localization of nonpalpable breast cancer is essential to achieve complete resection. Radioguided occult lesion localization (ROLL) has been introduced as an alternative for wire-guided localization (WGL). Although efficacy of ROLL has been established in a randomized controlled trial, cost-effectiveness of ROLL compared with WGL is not yet known. The objective of this study was to determine whether ROLL has acceptable cost-effectiveness compared with WGL. METHODS: An economic evaluation was performed along with a randomized controlled trial (ClinicalTrials.gov, No. NCT00539474). Women (>18 years) with histologically proven nonpalpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomized to ROLL (n = 162) or WGL (n = 152). Empirical data on direct medical costs were collected, and changes in quality of life were measured over a 6-month period. Bootstrapping was used to assess uncertainty in cost-effectiveness estimates, and sensitivity of the results to the missing data approach was investigated. RESULTS: In total, 314 patients with 316 invasive breast cancers were enrolled. On average ROLL required the same time as WGL for the surgical procedure (119 vs 118 min), resulted in a 7 % higher reinterventions risk, and 13 % more complications. Quality of life effects were similar (difference 0.00 QALYs 95 % CI (-0.04-0.05). Total costs were also similar for ROLL and WGL (+26 per patient 95 % CI -250-311). CONCLUSION: ROLL is comparable to WGL with respect to both costs and quality of life effects as measured with the EQ5D and will therefore not lead to more cost-effective medical care.

Sentinel lymph node biopsy of the internal mammary chain in breast cancer.

Routine removal of the internal mammary chain (IMC) sentinel node in breast cancer patients remains a subject of discussion. The aim of this study was to determine the impact of routinely performed IMC sentinel node biopsy on the systemic and locoregional treatments plan. All patients with biopsy proven breast cancer who underwent a sentinel node procedure between 2002 and 2011 were included in a prospective database. In cases of IMC drainage, successful exploration of the IMC (i.e., sentinel node removed) and surgical complications were registered. If the removed sentinel node contained malignant cells we determined if this altered the treatment plan when practising the current guidelines. In total, 119 of the 493 included patients showed IMC drainage on lymphoscintigraphy. Exploration of the IMC was performed in 107 (89 %) patients; in 86/107 (80 %) exploration was successful. In 14/107 patients (13 %) the IMC sentinel node was tumor positive. Macro and micro metastases were found in eight and six patients, respectively. In the group of patients who underwent surgical exploration of the IMC, systemic treatment was changed in none, radiotherapy treatment in 13/107 patients (11 %). Routine sentinel node biopsy of the IMC does not alter the systemic treatment. Radiotherapy treatment is altered in a small proportion of the patients; however, solid scientific evidence for this adjustment is lacking.

Efficacy of 'radioguided occult lesion localisation' (ROLL) versus 'wire-guided localisation' (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial.

For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisation. Women (>18 years.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99 m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with negative margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86 %) patients in the ROLL group versus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) patients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). No significant differences were seen in the duration and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first multicentre randomised controlled comparison of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care.

Robotic nipple-sparing mastectomy complication rate compared to traditional nipple-sparing mastectomy: a systematic review and meta-analysis.

Breast cancer is worldwide the most common cause of cancer in women and causes the second most common cancer-related death. Nipple-sparing mastectomy (NSM) is commonly used in therapeutic and prophylactic settings. Furthermore, (preventive) mastectomies are, besides complications, also associated with psychological and cosmetic consequences. Robotic NSM (RNSM) allows for better visualization of the planes and reducing the invasiveness. The aim of this study was to compare the postoperative complication rate of RNSM to NSM. A systematic search was performed on all (R)NSM articles. The primary outcome was determining the overall postoperative complication rate of traditional NSM and RNSM. Secondary outcomes were comparing the specific postoperative complication rates: implant loss, hematoma, (flap)necrosis, infection, and seroma. Forty-nine studies containing 13,886 cases of (R)NSM were included. No statistically significant differences were found regarding postoperative complications (RNSM 3.9%, NSM 7.0%, p = 0.070), postoperative implant loss (RNSM 4.1%, NSM 3.2%, p = 0.523), hematomas (RNSM 4.3%, NSM 2.0%, p = 0.059), necrosis (RNSM 4.3%, NSM 7.4%, p = 0.230), infection (RNSM 8.3%, NSM 4.0%, p = 0.054) or seromas (RNSM 3.0%, NSM 2.0%, p = 0.421). Overall, there are no statistically significant differences in complication rates between NSM and RNSM.

Inter-method reliability of the modified Rankin Scale in patients with subarachnoid hemorrhage.

BACKGROUND AND OBJECTIVES: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS. METHODS: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire. RESULTS: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible. DISCUSSION: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials. TRIAL REGISTRATION: www.trialregister.nl ; Unique identifier: NL7859.

Genetic and environmental sources of covariance among internal reproductive traits in the yellow dung fly.

Substantial inter- and intraspecific variation is found in reproductive traits, but the evolutionary implications of this variation remain unclear. One hypothesis is that natural selection favours female reproductive morphology that allows females to control mating and fertilization and that diverse male reproductive traits arise as counter adaptations to subvert this control. Such co-evolution predicts the establishment of genetic correlations between male and female reproductive traits that closely interact during mating. Therefore, we measured phenotypic and genetic correlations between male and female reproductive tract characteristics in the yellow dung fly, Scathophaga stercoraria (Diptera: Scathophagidae), using a nested half-sib breeding experiment. We found significant heritabilities for the size of most reproductive tract traits investigated in both females (spermathecae and their ducts, accessory glands and their ducts) and males (testis size but not sperm length). Within the sexes, phenotypic and genetic correlations were mostly nil or positive, suggesting functional integration of or condition-dependent investment in internal reproductive traits. Negative intrasexual genetic correlations, potentially suggestive of resource allocation trade-offs, were not evident. Intersexual genetic correlations were mostly positive, reflecting expected allometries between male and female morphologies. Most interestingly, testis size correlated positively with female accessory gland size and duct length, potentially indicative of a co-evolutionary arms race. We discuss these and alternative explanations for these patterns of genetic covariance.

Investigating morphological changes in the brain in relation to etiology and duration of olfactory dysfunction with voxel-based morphometry.

Olfactory loss (OL) affects up to 20% of the general population and is related to changes in olfaction-related brain regions. This study investigated the effect of etiology and duration of OL on gray matter volume (GMV) of these regions in 257 patients. Voxel-based morphometry was applied to measure GMV in brain regions of interest to test the effects of etiology and duration on regional GMV and the relation between olfactory function and regional GMV. Etiology of OL had a significant effect on GMV in clusters representing the gyrus rectus and orbitofrontal cortex (OFC), bilaterally. Patients with congenital anosmia had reduced GMV in the gyrus rectus and an increased OFC volume compared to patients with acquired OL. There was a significant association between volume of the left OFC and olfactory function. This implies that changes in GMV in patients with acquired OL are mainly reflected in the OFC and depend on olfactory function. Morphology of olfactory areas in the brain therefore seems to relate to olfactory function and the subsequent degree of exposure to olfactory input in patients with acquired OL. Differences in GMV in congenital anosmia are most likely due to the fact that patients were never able to smell.

Inbred women in a small and isolated Swiss village have fewer children.

Despite overwhelming evidence for a negative effect of inbreeding on fitness in plants and nonhuman animals, the exact nature of its effect in humans remains subject to debate. To obtain a better understanding of the effects of inbreeding on reproductive success in humans, we reconstructed the genealogies of the current inhabitants of a small and isolated Swiss village and used these to estimate the level of inbreeding of both members of all married couples, as well as their relatedness (i.e. the level of inbreeding of their offspring). Although there was no effect of parental relatedness on the number of children a couple had, we found that inbred mothers, but not inbred fathers, had significantly fewer children. Thus, although related couples did not have fewer children themselves, their inbred daughters did leave them with fewer grandchildren. Thereby, we provide evidence for the existence of inbreeding depression in human fertility, also in relatively outbred and egalitarian communities.

Chemosensory perception and food preferences in colorectal cancer patients undergoing adjuvant chemotherapy.

BACKGROUND AND AIM: Cancer is one of the major public health problems, with colorectal cancer being one of the most occurring types of cancer. During treatment, patients may experience changes in their dietary intake due to side-effects of treatment, like changes in chemosensory perception, i.e. smell and taste function. This study investigated alterations in chemosensory perception and food preferences in colorectal cancer patients during and after adjuvant chemotherapy. METHODS: Objective olfactory and gustatory function were measured by the Sniffin' Sticks and the Taste Strips test. Subjective smell and taste perception were determined with a questionnaire, while food preferences were assessed with a computer-based ranking task. To investigate changes during chemotherapy, patients undergoing adjuvant chemotherapy were measured before the start, halfway through (approximately 3 months after the start of adjuvant chemotherapy), and within one month after finishing chemotherapy (longitudinal measurements, n = 15 patients). As a comparison group, colorectal cancer patients not undergoing chemotherapy (n = 20), underwent the same measurements at similar time points. To measure changes after treatment, chemosensory perception and food preferences of patients who had undergone chemotherapy treatment were measured once, either at 6, 12 or 24 months after diagnosis (cross-sectional measurements; n = 20 for all time points). Changes during treatment were assessed using linear mixed model analyses, and changes after treatment were assessed with a one-way ANOVA or a Kruskal Wallis test. RESULTS: Objective olfactory and gustatory function did not differ statistically significantly between any of the groups and at any time point during or after treatment (all p > 0.05). In contrast, subjective smell (F(1,84) = 8.17, p = 0.005) and taste (F(1,99) = 4.08, p = 0.046) perception were rated statistically significantly lower by patients undergoing chemotherapy than the comparison group during treatment. At 6 months after diagnosis, patients who underwent chemotherapy rated their subjective taste perception significantly lower than patients at 12 and 24 months after treatment (F(2,57) = 12.05, p = 0.002). Food preferences did not change during treatment, or thereafter (all p > 0.05). Preference for protein-rich foods was positively correlated with objective gustatory function (r = 0.36, p < 0.001), while the preference for low-energy foods showed a negative correlation with objective gustatory function (r = -0.28, p = 0.004). CONCLUSIONS: Similar to other cancer patient populations, mainly subjective smell and taste perception are affected in colorectal cancer patients undergoing adjuvant chemotherapy. Changes in objective olfactory and gustatory function in relation to chemotherapy were not detected by the tests used in our study nor did food preferences change. However, it should be noted that subjective changes in smell and taste perception can affect subsequent flavor perception and food enjoyment, which might negatively impact eating behavior and nutritional intake.

Short- and long-term consequences of early developmental conditions: a case study on wild and domesticated zebra finches.

Divergent selection pressures among populations can result not only in significant differentiation in morphology, physiology and behaviour, but also in how these traits are related to each other, thereby driving the processes of local adaptation and speciation. In the Australian zebra finch, we investigated whether domesticated stock, bred in captivity over tens of generations, differ in their response to a life-history manipulation, compared to birds taken directly from the wild. In a 'common aviary' experiment, we thereto experimentally manipulated the environmental conditions experienced by nestlings early in life by means of a brood size manipulation, and subsequently assessed its short- and long-term consequences on growth, ornamentation, immune function and reproduction. As expected, we found that early environmental conditions had a marked effect on both short- and long-term morphological and life-history traits in all birds. However, although there were pronounced differences between wild and domesticated birds with respect to the absolute expression of many of these traits, which are indicative of the different selection pressures wild and domesticated birds were exposed to in the recent past, manipulated rearing conditions affected morphology and ornamentation of wild and domesticated finches in a very similar way. This suggests that despite significant differentiation between wild and domesticated birds, selection has not altered the relationships among traits. Thus, life-history strategies and investment trade-offs may be relatively stable and not easily altered by selection. This is a reassuring finding in the light of the widespread use of domesticated birds in studies of life-history evolution and sexual selection, and suggests that adaptive explanations may be legitimate when referring to captive bird studies.