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Multiple myeloma (MM) remains incurable. Although early diagnosis improves outcomes, it has been unclear which populations to target for screening with serum electrophoresis, serum free light chains and urine electrophoresis. Here, we assessed the value of MM screening in a Fracture Liaison Service, finding that 1 per 195 fragility fractures has undiagnosed MM, which can be expedited to Haematology Services. Purpose A key role of the Fracture Liaison Service (FLS) is screening for secondary causes of osteoporosis. In 2019, the Royal Osteoporosis Society recommended that all patients attending FLS who are recommended anti-osteoporosis therapy have universal screening for myeloma based on serum electrophoresis, serum free light chains and urine electrophoresis. Here, we examined the impact of universal myeloma screening within an FLS. Methods We sampled all patients seen by the Oxfordshire FLS between January and April 2018. The completion rates and outcomes of screening were checked using the hospital and FLS databases. Results Of 950 patients identified by the FLS, 628 were eligible for MM screening; 473 (75%) of these were female, and the average age was 78.4 years. Overall, 584 had some form of myeloma screening, of which 577 (92%) had serum electrophoresis, 525 (84%) had serum free light chains and 407 (65%) had urine electrophoresis measured. A total of 327 (59%) patients had complete screening. Three patients (0.5%) had newly diagnosed myeloma and were urgently referred to Haematology Services. Furthermore, 46 (8%) patients had a detectable serum paraprotein with a likely diagnosis of monoclonal gammopathy of uncertain significance (MGUS) and referred for community annual surveillance according to local guidelines. Conclusion Addition of universal myeloma screening to laboratory testing identified myeloma in 1 per 195 patients, and its precursor state MGUS in 1 per 13 patients, which may have otherwise been missed. Further analysis with long-term follow-up is needed to clearly define the value of diagnosing MGUS within the FLS setting and establish the benefits vs. costs and methods to improve screening completion rates.

A single pulse of high intensity electrical current delivered to the digits of the hand during voluntary contractions produces a period of decreased electromyographic (EMG) activity, known as a cutaneous silent period (CSP) (Caccia and Violini, 1973; Inghilleri et al., 1997; Uncini et al., 1991). Pairing transcranial magnetic stimulation (TMS) with digit stimulation results in motor evoked potentials (MEPs) with reduced amplitudes in a thenar muscle (Kofler, 2008). It is not known if similar behavior can be observed in more proximal upper-limb muscles. The current study investigated the CSP on several muscles throughout the upper-limb. Fourteen subjects performed isometric contractions with the following muscles: abductor pollicis brevis (APB), flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BIC), triceps brachii (TRI), anterior deltoid (AD), and posterior deltoid (PD). During the isometric contractions, subjects experienced three different stimulation conditions: electrical stimulation (10x perceptual threshold) of digit II only (CSP), transcranial magnetic stimulation only (TMS), and a pairing of digit II stimulation and TMS (TMS+). The TMS evoked MEP was significantly greater than the TMS+ MEP for APB (p 0.001), FCR (p = 0.006), and BIC (p 0.049) muscles. The opposite relationship was seen within the PD (p 0.047) muscle. An ANOVA test of normalized MEP values (TMS+/TMS) showed significant differences in APB vs TRI (p = 0.004) and PD (p = 0.003), and in FCR vs TRI (p = 0.046) and PD (p = 0.037) muscles. The results suggest that the CSP modulates descending drive differentially across upper-limb muscles.

Multiple myeloma (MM) remains incurable. Although early diagnosis improves outcomes, it has been unclear which populations to target for screening with serum electrophoresis, serum free light chains and urine electrophoresis. Here, we assessed the value of MM screening in a Fracture Liaison Service, finding that 1 per 195 fragility fractures has undiagnosed MM, which can be expedited to Haematology Services.A key role of the Fracture Liaison Service (FLS) is screening for secondary causes of osteoporosis. In 2019, the Royal Osteoporosis Society recommended that all patients attending FLS who are recommended anti-osteoporosis therapy have universal screening for myeloma based on serum electrophoresis, serum free light chains and urine electrophoresis. Here, we examined the impact of universal myeloma screening within an FLS.We sampled all patients seen by the Oxfordshire FLS between January and April 2018. The completion rates and outcomes of screening were checked using the hospital and FLS databases.Of 950 patients identified by the FLS, 628 were eligible for MM screening; 473 (75%) of these were female, and the average age was 78.4 years. Overall, 584 had some form of myeloma screening, of which 577 (92%) had serum electrophoresis, 525 (84%) had serum free light chains and 407 (65%) had urine electrophoresis measured. A total of 327 (59%) patients had complete screening. Three patients (0.5%) had newly diagnosed myeloma and were urgently referred to Haematology Services. Furthermore, 46 (8%) patients had a detectable serum paraprotein with a likely diagnosis of monoclonal gammopathy of uncertain significance (MGUS) and referred for community annual surveillance according to local guidelines.Addition of universal myeloma screening to laboratory testing identified myeloma in 1 per 195 patients, and its precursor state MGUS in 1 per 13 patients, which may have otherwise been missed. Further analysis with long-term follow-up is needed to clearly define the value of diagnosing MGUS within the FLS setting and establish the benefits vs. costs and methods to improve screening completion rates.

Compared to other species of Candida yeasts, the growth of Candida glabrata was inhibited by many different strains of Saccharomyces killer yeasts. The ionophoric K1 and K2 killer toxins were broadly inhibitory to all clinical isolates of C. glabrata from patients with recurrent vulvovaginal candidiasis despite high levels of resistance to clinically relevant antifungal therapeutics.

Ausgehend vom Gesundheitsbegriff der WHO, wird anhand der Geschichte der Korperpsychotherapie herausgearbeitet, wie sich das Verstandnis von Korper und Gesundheit verandert und ausdifferenziert hat. Seit Beginn des 20. Jahrhunderts geht es in der Korperpsychotherapie um die Entfaltung menschlicher Potenziale, die mit der Befreiung von individuellen und gesellschaftlichen Zwangen begannen. Die reformgymnastische Bewegung Elsa Gindlers, die Forschungen Wilhelm Reichs sowie achtsamkeitsbasierte Korperpsychotherapieformen beleuchten unterschiedliche Aspekte von Korper und Gesundheit sowie verschiedene Wege des Zugangs. Die gesellschaftliche Relevanz ihrer Ziele ist bis heute gultig.

Temporal summation of second pain (TSSP) is a psychophysical indication of a central pain encoding mechanism, potentially enhanced in pathological pain conditions. Low-frequency repetitive stimulation of unmyelinated (C) nociceptors results in a progressive increase of pain intensity when thermal stimulation intensity remains constant. However, when using different methods of nociceptive delivery to the skin, regularity as well as rate of pain enhancement with repetition varies between experiments. Specifically, repetitive ramping up and down from a neutral to a painful temperature has produced weak and inconsistent pain summation. In contrast, repetitive contact of the skin with a preheated probe has generated substantial pain summation. In the present study, TSSP by the intermittent contact with a preheated thermode and constant contact, ramp and hold methods were compared during 10 iterations of stimulation of glabrous skin of the hand or hairy forearm skin, with an onset to onset interval of 3.3 seconds and stimulus interval of .8 seconds. Significantly greater TSSP was observed for intermittent contact stimulation at both sites (P .001). Differential activation of myelinated and unmyelinated nociceptors by ramping and tapping may account for different rates of temporal summation of heat pain.This article presents direct evidence suggesting the constant contact, ramp and hold stimulus may underestimate the level of TSSP. This evidence suggests the re-evaluation of stimulation techniques used for temporal summation tests, especially within clinical models.

© 2017 IEEE. This paper presents an analysis of the direct- and quadrature-axis inductances for linear tubular actuators with permanent magnet arrays, highlighting and featuring how they are affected by the end effects. A semi-analytical and an experimental analysis are performed to prove the influence of end effects on self- and mutual inductances. The synchronous parameters, i.e., d - and q -axis inductances of the actuator, are determined using a semi-analytical method and an experimental method. Once the synchronous parameters are all identified, high performance control methods (such as direct force control and vector control) may be implemented.

Acute pain arises from activation of myelinated (A delta) and unmyelinated (C) nociceptive afferents, leading to first (A-fiber) or second (C-fiber) pain sensations. The current study sought to investigate first and second pain within glabrous and hairy skin sites in human upper limbs. Fifty healthy adults (25 male/25 female, 18–30 years old, mean = 20.5 ± 1.4 years) participated in a psychophysical study investigating electronically rated, thermal first and second pain sensations within the glabrous skin at the palm and hairy skin of the forearm. Repeated measures analysis of variance indicated that the threshold for first pain was lower (more sensitive) than for second pain ( P = .004), for glabrous as well as hairy skin, and thresholds at glabrous skin were higher than for hairy skin ( P = .001). Hairy skin presented a steeper slope for testing, whereas there were no differences in slope between first and second pain. The study findings support assumptions associated with mechanistic differences between first and second pain sensations, while offering a novel method for producing first and second pain with the same thermal stimulus. Efforts to understand abnormalities among people with clinical pain and development of new therapeutic agents will benefit from specific psychophysical methods. Perspective This article presents a novel method for directly comparing first and second pain within the same thermal stimulus. The ability to directly compare first and second pain sensations can aid in understanding pain abnormalities in clinical pain and development of therapeutic aids.

This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), in magnitude as well as time course. Eight younger and 9 older adults underwent 3 experimental sessions using well validated laboratory pain models: cold pressor task, contact heat pain, and a nonpainful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60 minutes after stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared with younger adults. After the cold pressor task, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. After heat pain, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the nonpainful control session. Perspective Older adults had higher baseline levels of substance P and β-endorphin suggesting increased peripheral activity compared with younger adults. After pain evocation, older adults demonstrated a more intense early response for both neuropeptides suggesting peripheral mechanisms involved in the response to pain may change with age.

The present study investigated the relations between morally disengaged attitudes, psychopathic affective traits, and a variety of antisocial and risky behaviors in a sample of adults (N = 181). A second aim of the study was to examine the unique contributions of moral disengagement and psychopathic traits in predicting problematic behavior while the other construct is statistically controlled. Results indicated that whereas psychopathic traits and moral disengagement were both uniquely predictive of non-violent antisocial behaviors, only remorselessness was uniquely predictive of violence and only morally disengaged attitudes were uniquely predictive of academic cheating. Differing relationships also emerged by gender.

We present an optical system which integrates a plasmonic sensing surface and an angular tracking system to enable a compact refractive index measurement. A refractive index change at the surface of the sensing membrane causes a change in the angle at which monochromatic light is transmitted through the membrane. This transmission angle is measured by the angular tracking system. We show good theoretical and experimental agreement of the transmission of the plasmonic sensing surface at different angular illumination of the membranes. Using this compact optical setup the embedded angular tracking system has an accuracy of

Streptococcus mutans has been implicated as the major acid-producing (cariogenic) bacterium. Dietary sugars and other factors may cause an imbalance of oral microflora that enables S. mutans to become dominant in the multi-species biofilms on the tooth surface, which could lead to dental caries. The application of broad-spectrum antimicrobials often results in re-colonization and re-dominance of S. mutans within oral flora, while in contrast, therapies capable of selective elimination of S. mutans from oral microbial communities may help to re-establish the normal flora and provide long-term protection. C16G2, a novel synthetic antimicrobial peptide with specificity for S. mutans, was found to have robust killing efficacy and selectivity for S. mutans in vitro. A subsequent pilot human study found that a single application of C16G2 in the oral cavity (formulated in a mouthrinse vehicle) was associated with a reduction in plaque and salivary S. mutans, lactic acid production, and enamel demineralization during the entire 4-day testing period. C16G2 is now being developed as a new anticaries drug.

PurposeThis paper seeks to explain Financial Industry Regulatory Authority (“FINRA”) Rule 4530, which requires members to report to FINRA certain internal and external findings of violative conduct and quarterly statistical and summary customer complaint information.Design/methodology/approachThe paper explains the background and provides an overview of FINRA Rule 4530; analyzes key provisions of the Rule, including the way it differs from legacy NASD and New York Stock Exchange Reporting Rules; and discusses next steps for FINRA members.FindingsFINRA Rule 4530 requires members to promptly report findings of internal and external violations and provides interpretive guidance regarding these requirements. The new Rule imposes obligations beyond those set forth in current NASD Rule 3070, requires reporting of internal findings, and alters the now familiar materiality standard applied to NYSE Rule 351(a).Practical implicationsThe new Rule will require members to enhance their policies and procedures to address the reporting of internal findings to define potentially reportable violations, identify decision‐makers to assess potential violations, create or modify reporting escalation procedures, and institute appropriate controls over reporting. Members may want to review their internal audit processes to reflect the new guidance regarding reporting based on internal findings of violations.Originality/valueThe paper provides practical guidance from expert securities lawyers.

Controlled-environment and field experiments were done to investigate effects of the fungicide Punch C (flusilazole plus carbendazim) on growth of Leptosphaeria maculans and L. biglobosa in oilseed rape. In controlled-environment experiments, for plants inoculated with L. maculans, fungicide treatment decreased lesion size and amount of L. maculans DNA in leaves; for plants inoculated with L. biglobosa, fungicide did not affect lesion size or amount of pathogen DNA. When release of ascospores was monitored using a Burkard spore sampler, the timing and pattern of ascospore release differed between the four seasons. In 2006/2007, the majority of ascospores released were L. maculans, whilst in 2007/2008 the majority were L. biglobosa; in both seasons L. maculans ascospores were released before L. biglobosa ascospores. In field experiments in 2002/2003 and 2003/2004, fungicide treatment decreased severity of stem canker on cv. Apex, but gave no significant yield response. In 2006/2007 and 2007/2008, fungicide treatment decreased phoma leaf spot incidence in autumn and stem canker severity at harvest, and increased yield. Fungicide treatment decreased stem canker severity more on cv. Courage, with a good yield response, than on cv. Canberra. In 2002/2003 and 2003/2004, fungicide treatment decreased the frequency of spread of L. maculans into stem pith tissues and in 2006/2007 fungicide decreased the amount of L. maculans DNA in stem tissues (measured by quantitative PCR). These results are used to suggest how effects of fungicides on interactions between L. maculans and L. biglobosa might affect severity of phoma stem canker and yield response.

CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.

BACKGROUND Ablative fractional photothermolysis (AFP) has been reported to be effective in the treatment of photoaging. MATERIALS AND METHODS Treatment was administered using an AFP device and assessed photographically 3 months after treatment by a blinded physician. Ultrasound measurements evaluated skin thickness and subepidermal low echogenic band thickness (SLEB), the portion of the papillary dermis filled with solar elastosis. RESULTS Three months after treatment, the mean score improved 61.0% (95% confidence interval (CI)=56.8–65.2%) for dyschromia, 54.3% (95% CI=51.6–57.0%) for skin laxity, 51.5% (95% CI=49.6–53.4%) for rhytides, and 60.2%9 (95% CI=56.8–63.6%) for overall cosmetic outcome. Patients had a significant decrease in SLEB in all anatomic sites treated (0.078 cm at baseline, 0.038 cm at 3 months, 40.0% decrease) (p

Thirty-four species of the genus Plectranthus (including species of the former genera Coleus and Solenostemon, fam. Lamiaceae) were surveyed for exudate flavonoids to see whether the distribution of these compounds would support a recent classification of the genus based on molecular and morphological characters. In this classification two major groups had been identified, the Coleus and Plectranthus clades. Only about 40% of the species, predominantly from the Plectranthus clade, were found to produce exudate flavonoids, which were mainly flavones. Flavanones were restricted to five species of the Plectranthus clade, whereas flavonols were only found in two species of the Coleus clade, Plectranthus montanus Benth. (synonyms Plectranthus marrubioides Hochst. ex Benth. and Plectranthus cylindraceus Hochst. ex Benth.) and Plectranthus pseudomarrubioides R.H.Willemse. Four of these flavonols were isolated from P. montanus and identified by NMR spectroscopy as the 3,7-dimethyl ether and 3,7,4′-trimethyl ether of quercetin and the 3,6,7-trimethyl ether and 3,6,7,4′-tetramethyl ether of quercetagetin. The remaining flavonols and flavones were identified by HPLC–UV and LC–MS of crude extracts on the basis of their UV and mass spectra, retention times and comparison with standards. Most flavonols were 3-methyl ethers and many of the flavones and flavonols were oxygenated at the 6-position. The most common flavones, occurring in both clades, were cirsimaritin and salvigenin, which are methoxylated at the 6- and 7-positions. 6-Hydroxylated flavones such as scutellarein and ladanein were restricted to species of the Plectranthus clade.

BACKGROUND: Phoma stem canker, caused by the coexisting related fungal pathogens Leptosphaeria maculans (Des.) Ces. & de Not and L. biglobosa Shoemaker & H Brun, is a major disease of winter oilseed rape in the UK. Annually, over 90% of UK crops receive at least one foliar application of fungicide, but little is known about the sensitivity of the more damaging L. maculans and the less damaging L. biglobosa to these fungicides. The effects of flusilazole, tebuconazole and Methyl Benzimidazole Carbamate (MBC) fungicides (benomyl and carbendazim) on the germination of ascospores, conidia and germ tube growth of both species were examined. Isolates collected from different oilseed rape crops in England and Wales were assessed for their mycelial growth on fungicide-amended medium, and ED50 values were calculated. RESULTS:Leptosphaeria maculans and L. biglobosa differed in their sensitivity to fungicides. Conidial germination of L. maculans was more sensitive to these fungicides than that of L. biglobosa. Isolates of L. maculans had smaller ED50 values for mycelial growth for all fungicides tested than isolates of L. biglobosa. CONCLUSION: These results suggest that fungicide applications might affect the structure of L. maculans/L. biglobosa populations in UK winter oilseed rape crops. Copyright © 2009 Society of Chemical Industry

The working electrode of a dye-sensitized photovoltaic fiber is constituted of a porous TiO2 coated titanium wire. The cohesion and adhesion of such a brittle oxide coating on the ductile metal substrate are identified as crucial factors in maintaining photovoltaic efficiency during textile manufacture and weaving operations. The influence of coating thickness on these factors has been investigated in the present work. The tensile mechanical characterization with in situ microscopic observations shows that two damaging processes are involved. For the smaller thickness, loss of adherence appears to be at the interface and inside the coating bulk. Cracks become visible in a random distribution in size and density and do not cross the entire coating circumference. Large patches of coating are still anchored on the wire. For the larger thickness no cohesive rupture in the coating bulk has been observed. The loss of adherence appears at the interface closed to the cracks and grows rapidly as the strain increases. Numerical investigations based on the finite element method permit to analyze the distribution and the combination of radial interfacial stress and circumferential coating stress and their influence on the observed damage.

Die Nachsorge von Patienten nach Primärbehandlung einer Tumorerkrankung wird aufgrund teilweise widersprüchlicher Empfehlungen und dem Fehlen von evidenzbasierten Daten bei vielen Erkrankungen unterschiedlich gehandhabt. Nur bei wenigen Krankheiten besteht ein kurativer Ansatz oder zumindest die Chance einer deutlichen Verbesserung der Lebenserwartung bei der Diagnose eines asymptomatischen Rezidivs. Für eine weitaus grössere Zahl von Krankheitsbildern ist eine symptomorientierte Nachsorge angezeigt, die Schwerpunkte auf Aspekte der Lebensqualität, aber auch auf Behandlungskomplikationen legen sollte. Psychologische Aspekte der ärztlichen Begleitung sind von besonderer Bedeutung. Bei Abneigung von Patienten gegen regelmässige Nachsorgetermine oder bei Fehlen von Interventionsmöglichkeiten kann sich die Tumornachsorge auf Arztkontakte bei Beschwerden oder bei Krankheitssymptomen beschränken. Der Artikel empfiehlt Vorgehensweisen bei der Nachsorge häufiger Tumorkrankheiten insbesondere auf der Grundlage der Empfehlungen der Europäischen Krebsgesellschaft ESMO.

Summary Leptosphaeria maculans, a Dothideomycete causing stem canker on oilseed rape (Brassica napus), develops gene-for-gene interactions with its host plants. To date, nine resistance genes (Rlm1–9) have been identified in Brassica spp. The corresponding nine avirulence genes (AvrLm1–9) in L. maculans have been mapped at four independent loci, thereby revealing two clusters of three and four linked avirulence genes. Here, we report the completion of map-based cloning of AvrLm1. AvrLm1 was genetically delineated within a 7.3 centimorgan interval corresponding to a 439 kb BAC contig. AvrLm1 is a single copy gene isolated within a 269 kb non-coding, heterochromatin-like region. The region comprised a number of degenerated, nested copies of four long-terminal repeat (LTR) retrotransposons, including Pholy and three novel Gypsy-like retrotransposons. AvrLm1 restored the avirulent phenotype on Rlm1 cultivars following functional complementation of virulent isolates. AvrLm1 homologues were not detected in other Leptosphaeria species or in known fungal genomes including the closely related species Stagonospora nodorum. The predicted AvrLm1 protein is composed of 205 amino acids, of which only one is a cysteine residue. It contains a peptide signal suggesting extracellular localization. Unlike most other fungal avirulence genes, AvrLm1 is constitutively expressed, with a probable increased level of expression upon plant infection, suggesting the absence of tight regulation of AvrLm1 expression.

Leptosphaeria maculans is the most ubiquitous fungal pathogen of Brassica crops and causes the devastating stem canker disease of oilseed rape worldwide. We used minisatellite markers to determine the genetic structure of L. maculans in four field populations from France. Isolates were collected at three different spatial scales (leaf, 2-m 2 field plot, and field) enabling the evaluation of spatial distribution of the mating type alleles and of genetic variability within and among field populations. Within each field population, no gametic disequilibrium between the minisatellite loci was detected and the mating type alleles were present at equal frequencies. Both sexual and asexual reproduction occur in the field, but the genetic structure of these populations is consistent with annual cycles of randomly mating sexual reproduction. All L. maculans field populations had a high level of gene diversity ( H = 0.68 to 0.75) and genotypic diversity. Within each field population, the number of genotypes often was very close to the number of isolates. Analysis of molecular variance indicated that >99.5% of the total genetic variability was distributed at a small spatial scale, i.e., within 2-m 2 field plots. Population differentiation among the four field populations was low ( G ST < 0.02), suggesting a high degree of gene exchange between these populations. The high gene flow evidenced here in French populations of L. maculans suggests a rapid countrywide diffusion of novel virulence alleles whenever novel resistance sources are used.

Kolorektale Karzinome gehören zu den häufigsten Tumorerkrankungen. Effiziente Strategien in ihrer Prävention und Behandlung werden daher unmittelbar zu einer relevanten Reduktion von Todesfällen führen. Neben einer Primärprävention durch Änderung von Lebens- und Ernährungsgewohnheiten kommt insbesondere einem wirksamen Massenscreening grosse Bedeutung zu.Eine komplette Resektion ist die Voraussetzung zur Heilung. Als neue Techniken setzen sich die totale mesorektale Exzision des Rektumkarzinoms und die laparoskopische Operation bei früheren Krankheitsstadien durch. Die adjuvante Therapie senkt beim Rektumkarzinom im Stadium II und III und beim Kolonkarzinom im Stadium III signifikant das Rückfallrisiko. Die dazu geeignetsten Strategien werden derzeit neu definiert.In der palliativen Therapie der metastasierten Erkrankung hat die Erweiterung des Medikamentenarsenals eine deutliche Verbesserung von Ansprechraten und Überlebenszeiten, aber auch Unsicherheiten über die optimale Abfolge der Therapieoptionen mit sich gebracht. Derzeit besteht die erfolgversprechendste Strategie in der Sequenz mehrerer Medikamentenkombinationen. Die operative Resektion lokalisierter hepatischer, aber auch pulmonaler Metastasen kann für einige Patienten eine kurative Chance darstellen.

The adipocyte fatty acid-binding protein (A-FABP) and leptin receptor (LEPR) genes are candidate quantitative trait loci (QTLs) for fatness traits in the pig. In both genes polymorphic short tandem repeat (STR) sequences in intron 1 (A-FABP) and in intron 3 (LEPR) were revealed. The association studies between both polymorphisms and productive traits were performed in two breeds (Polish Large White and Polish Landrace) and one synthetic line (L990) of the pig. In the A-FABP ten and in the LEPR gene eight alleles were identifi ed, and the polymorphic information content (PIC) values ranged from 0.713 to 0.749 and from 0.441 to 0.557, respectively. The associations with backfat thickness and intramuscular fat content were found. Since the observed relationships considering each gene were not concordant in all the studied populations, it was concluded that both genes are linked with an unknown QTL.

Summary Porcine leptin gene (LEP) and its association with production traits was analysed in the Polish Large White (PLW, n = 135), Polish Landrace (PL, n = 120) and synthetic line 990 (L990, n = 184). Two fragments of exon 3 of LEP were studied with the use of RFLP and SSCP techniques. The frequencies of C allele for the T3469C polymorphic site were 0.11, 0.10 and 0.11 in PLW, PL and L990, respectively. Phenotypic data were collected for the average daily weight gain, the feed conversion ratio, the weight of abdominal fat, backfat thickness (five measurements), intramuscular fat, meat content, loin weight, loin muscle area, ham weight and ham cut weight. The contrasts between TT and TC genotypes at the T3469C polymorphic site were estimated in the unitrait Animal Model with genotype at the RYR1 locus included. The lowest p values occurred for association test between T3469C polymorphism and intramuscular fat content in PLW (0.26 ± 0.14%, p = 0.05) and loin weight in L990 (−0.32 ± 0.13 kg, p = 0.01). We conclude that the detected associations are population-specific and the analysed polymorphism of the LEP gene does not contribute directly to genetic variability of growth and carcass traits in pigs. Zusammenfassung Das porcine Leptin-Gen (LEP) und Assoziationen mit Produktionsmerkmalen wurden in der Polnischen Large White (PLW, n = 135), Polnischen Landrasse (PL, n = 120) und der Synthetischen Linie 990 (L990, n = 184) analysiert. Dazu wurden zwei Fragmente von Exon 3 des LEP mittels RFLP- und SSCP-Techniken untersucht. Die Frequenzen des C-Alleles fur die polymorphe Stelle T3469C betrugen 0,11, 0,10 beziehungsweise 0,11 in PWL, PL und L990. Phanotypische Daten wurden gesammelt fur die durchschnittliche Tageszunahme, die Futterverwertung, das Gewicht des abdominalen Fetts, die Ruckenspeckdicke (5 Messpunkte), das intramuskulare Fett, den Fleischanteil, das Lendengewicht, die Lendenmuskelflache, das Schinkengewicht (abgespeckt) und das Gesamtschinkengewicht. Die Gegensatze zwischen dem TT- und dem TC-Genotyp an der polymorphen Stelle T3469C wurden in einem Ein-Merkmal-Tier-Modell unter Einbeziehung des Genotyps am RYR1-Locus geschatzt. Die niedrigsten P-Werte traten beim Assoziationstest zwischen dem T3469C-Polymorphismus und dem intramuskularem Fettgehalt bei PWL (0,26 ± 0,14 %, p = 0,05) sowie dem Lendengewicht bei L990 (−0,32 ± 0,13 kg, p = 0,01) auf. Wir schliesen daraus, dass die nachgewiesenen Assoziationen populationsspezifisch sind und der analysierte Polymorphismus des LEP-Gens nicht direkt zur genetischen Variabilitat der Wachstums- und Schlachtkorpermerkmale in Schweinen beisteuert.

The fabrication of silicon cantilever-based scanning near-field optical microscope probes with fully aluminium-coated quartz tips was optimized to increase production yield. Different cantilever designs for dynamic- and contact-mode force feedback were implemented. Light transmission through the tips was investigated experimentally in terms of the metal coating and the tip cone-angle. We found that transmittance varies with the skin depth of the metal coating and is inverse to the cone angle, meaning that slender tips showed higher transmission. Near-field optical images of individual fluorescing molecules showed a resolution < 100 nm. Scanning electron microscopy images of tips before and after scanning near-field optical microscope imaging, and transmission electron microscopy analysis of tips before and after illumination, together with measurements performed with a miniaturized thermocouple showed no evidence of mechanical defect or orifice formation by thermal effects.