Auswahl der wissenschaftlichen Literatur zum Thema „Metamorphoses 12,1-13,622“

Abstract The Kozani earthquake (Ms = 6.6) of 13 May 1995 is the strongest event of the decade in Greece and occurred in a region of low seismic activity. Using regional data and the strong-motion record at the Kozani station, we relocate the mainshock at 40.183° N and 21.660° E, beneath the Vourinos massif at a depth of 14.2 km. We also compute a focal mechanism by body-waveform modeling at teleseismic distance, which confirms a normal mechanism. The most likely plane strikes 240° ± 1° N and dips 40° ± 1° N with a centroid depth of 11 ± 1 km. Modeling of the strong-motion record at Kozani confirms that nucleation started at the eastern termination of the bottom of the fault. Six days after the mainshock, we installed a network of 40 portable seismological stations for one week around the epicentral region. Several thousand aftershocks were recorded, among which we locate 622 with a precision better than 1 km. We compute 181 focal mechanisms that mostly show normal faulting. The aftershock seismicity is restricted between 5 and 15 km depth and defines a plane dipping north at an angle of about 35°, consistent with the mainshock mechanism. Seismic activity with the same pattern of normal fault mechanisms is also seen on an antithetic fault connected to the main one at 12 km depth, which cuts the ground surface north of the Vourinos ophiolite massif in the Siatista valley. These results suggest two possibilities for the active fault plane; either it is the Deskati fault that is flat and dips with a constant angle, and therefore the surface breaks are secondary features, or, more likely, it is the Paleohori fault that is new, of listric shape, and located ahead of the Deskati fault, which was not active during the earthquake.

Background CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "do not eat" signal to suppress macrophage phagocytosis. Overexpression of CD47 serves as a mechanism of immune surveillance evasion, and is found to be associated with poor prognosis in both hematologic and solid malignancies. TTI-622 is a fusion protein consisting of the CD47-binding domain of human SIRPα linked to the Fc region of human IgG4. It is designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc. Importantly, unlike many CD47-blocking agents, TTI-622 does not bind to human red blood cells. Methods TTI-622-01 is an ongoing multicenter, Phase 1 study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of TTI-622 in adult patients with relapsed/refractory (R/R) lymphoma (NCT03530683). Based on a modified 3+3 scheme, weekly doses are escalated through pre-planned dose levels ranging from 0.05 to 8 mg/kg. The observation period for dose limiting toxicity (DLT) is the initial 3 weeks of treatment. Safety monitoring includes weekly clinical laboratories and assessments of adverse events (AEs) based on CTCAE v 4.03. Blood samples are collected for PK analysis and assessment of receptor occupancy on normal peripheral T cells. Disease assessments are performed per Lugano criteria every 8 weeks within the first 6 months, every 3 months up to two years, and every 6 months thereafter until the end of treatment. Results As of the July 16, 2020 cutoff, 25 patients (12M/13F) with a median age of 68 years (range 24-86) have received dose levels of 0.05−8 mg/kg with testing at 8 mg/kg ongoing. Patients with the following histologies have been enrolled: diffuse large B-cell lymphoma (DLBCL; n=13), Hodgkin lymphoma (n=5), follicular lymphoma (FL; n=2), peripheral T-cell lymphoma (PTCL; n=2), cutaneous T-cell lymphoma with CD30 negative large cell transformation (CTCL-LCT, n=2), and mantle cell lymphoma (n=1). Disease stages at entry have been III or IV in 23 patients; patients had received a median of 3 (range 1-9) prior systemic therapies including CAR-T in 5 patients and HSCT in 6 patients. Treatment-related AEs have been reported in 12 (48%) patients. Most AEs have been grade 1 or 2. The most frequent treatment-related AEs include thrombocytopenia (n=4; 1 grade ≥3), neutropenia (n=3; 3 grade ≥3) and fatigue (n=3; 0 grade ≥3). Grade 4 thrombocytopenia occurred in 1 patient in the 8 mg/kg cohort and accounted for the only DLT and treatment-related serious AE reported to date. This event that occurred on Day 8 was not associated with bleeding and resolved within 1 day after prophylactic platelet transfusion. Mild to moderate platelet decreases seen in the majority of patients generally occurred on dosing days and recovered quickly to baseline levels. No other grade ≥3 thrombocytopenia have been observed in the 4 other DLT evaluable patients dosed with 8 mg/kg to date. Preliminary PK results suggest dose-dependent increases in exposure following both single and repeated TTI-622 infusions. PD results indicate that end-of-infusion CD47 receptor occupancy (RO) is above 60% at doses ≥2 mg/kg and that RO is more sustained with TTI-622 doses ≥1 mg/kg compared to lower doses. Objective responses have been achieved in 5 patients, including 1 complete response (CR) in DLBCL (0.8 mg/kg) and 4 partial responses (PR) in PTCL (2 mg/kg), DLBCL (4 mg/kg), CTCL-LCT and FL (8 mg/kg). Initial responses were achieved at the first disease assessment (week 8) in all 5 responders including initial PR in the patient who subsequently achieved CR at week 36 (See Figure 1). In the dose range of 0.8-8 mg/kg, objective responses occurred in 31% (5/16) of patients with ≥1 post-treatment response assessment (See Table 1). Two of 4 response evaluable patients in the ongoing 8 mg/kg cohort achieved a PR, and 2 other patients have been on treatment for <8 weeks. Conclusions Results to date from this ongoing Phase 1 study in patients with R/R lymphomas indicate that weekly doses of TTI-622 up to 4 mg/kg are well tolerated with dose-dependent increases in exposure and RO. TTI-622 has shown activity in R/R lymphoma with objective responses across a broad dose range (0.8-8 mg/kg) and in multiple histologies. The study is currently evaluating the 8 mg/kg dose level. Disclosures Patel: Pharmacyclics: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Kite: Consultancy; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy. Ramchandren:Seattle Genetics, Sandoz-Novartis, Pharmacyclics/Janssen, Bristol-Myers Squibb: Consultancy; Merck, Seattle Genetics, Janssen, Genentech: Research Funding. Lesokhin:Juno: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Janssen: Research Funding; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Takeda: Consultancy, Honoraria. von Keudell:Pharmacyclics: Research Funding; Genentech: Research Funding; Bayer: Research Funding. Cheson:Symbio: Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees; Jannsen: Consultancy; Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; TG Therapeutics: Speakers Bureau; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Kite: Consultancy; Parexel: Consultancy. Zonder:Intellia, Amgen, Takeda, Janssen, Regeneron, Alnylam, Caelum, Oncopeptides: Consultancy; BMS, Celgene: Research Funding. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Catalano:Trillium Therapeutics Inc.: Current Employment. Lin:Trillium Therapeutics Inc.: Current Employment. Uger:Trillium Therapeutics Inc.: Current Employment. Petrova:Trillium Therapeutics Inc.: Current Employment. Roberge:Trillium Therapeutics Inc.: Current Employment. Shou:Trillium Therapeutics Inc.: Current Employment. Iyer:Target Oncology: Honoraria; Seattle Genetics, Inc.: Research Funding; Rhizen: Research Funding; CRISPR: Research Funding; Curio Biosciences: Honoraria; Trillium: Research Funding; Daiichi Sankyo: Consultancy; Legend Biotech: Consultancy; Spectrum: Research Funding; Merck: Research Funding; Afffimed: Research Funding.

BackgroundGPs are crucial in adequately diagnosing and initiating appropriate management for patients with psychological problems, but face many challenges and require support.AimTo determine the effects of the e-tool PsyScan.Design and settingA randomised controlled trial with a 1-year follow-up, comparing care using PsyScan with usual care for psychological problems, was undertaken in 10 multidisciplinary primary healthcare centres in Eindhoven, the Netherlands.MethodBetween consultations with their GP, participants in the intervention group could complete PsyScan. The e-tool consists of a distress screener and Four-Dimensional Symptom Questionnaire to differentiate between stress, depression, anxiety, and somatisation symptoms, and to explore symptom severity. PsyScan generated diagnostic and therapeutic advice for GPs and participants that was automatically transferred to each patient’s electronic medical record. The primary outcome was the proportion of participants that achieved a successful treatment result; namely, a decrease of ≥50% on the Symptom Checklist-90-Revised, after 1 year.ResultsThere were 176 participants in the intervention group and 160 in the control group. After multiple imputation, the participants in the intervention group had higher chances of achieving a successful treatment result compared with those in the control group (odds ratio [OR] 2.7, 95% confidence interval [CI] = 1.5 to 4.8, P = 0.002). Quality of life was higher in the intervention group at 12 months (mean difference in EuroQol 5 Dimensions 5 Levels index values was 0.076, 95% CI = 0.015 to 0.136, P = 0.01). The mean 1-year costs per participant were similar (€13 622 in intervention group, €12 487 in control group [β = −0.03, P = 0.71, R2 = 0.05]).ConclusionPsyScan generated clinically relevant and statistically significant effects, and could be useful in offering effective individualised care to patients.

Background and purpose: In the past decade, a shift occurred in surgical total hip arthroplasty (THA) approaches to the posterolateral (PLA) and direct anterior approach (DAA). Comparisons of postoperative activities and participation between surgical approaches for THA are sparse. We therefore investigated the association between PLA and DAA for THA regarding the construct “activity and participation” (ICF model) during the first postoperative year.Patients and methods: This was an observational cohort study on osteoarthritis patients scheduled for primary THA in 2 hospitals. Questionnaires to assess the ICF domain “activity and participation” were completed preoperatively, and 3, 6, and 12 months postoperatively (HOOS Activities of daily living (ADL) and Sport and Recreation Function (SR), Hospital for Special Surgery Hip Replacement Expectations Survey, and questions regarding return to work). Each hospital exclusively performed one approach (PLA [Alloclassic-Zweymüller stem] or DAA [Taperloc Complete stem]) for uncemented THA. Hospital was included as instrumental variable, thereby addressing bias by (un)measured confounders. Adjusted mixed-effect models were used, stratified by employment.Results: Total population: 238 PLA (24% employed) and 622 DAA (26% employed) patients. At 12 months, the PLA group had a lower ADL score (–7, 95% CI –12 to –2 points). At 6 months, significantly fewer PLA patients had fulfillment of the expectation sports-performance (OR = 0.3, CI 0.2–0.7]. Other outcomes were comparable.Employed population: At 6 and 12 months, PLA patients scored clinically lower on ADL (respectively –10, CI –19 to 0 and –9, CI –19 to 0 points) and SR (respectively –13, CI –21 to –4 and –9, CI –18 to –1 points). At 6 months, fewer PLA patients fulfilled the expectation joining recreational activities (OR = 0.2, CI 0.1–0.7]. Fulfillment of other expectations was comparable between groups. PLA patients less often returned to work within 3 months (31% vs. 45%), but rates were comparable at 12 months (86% vs. 87%).Interpretation: Overall, functional recovery regarding “activity and participation” was comparable for PLA and DAA. Among employed patients, DAA resulted in better functional recovery and more fulfillment of expectations compared with PLA patients. DAA might also facilitate faster return to work.

To date there have been few reports on the impact of dietary intervention on the clinical course of acute shigellosis. Current management of acute shigellosis is primarily focused on antibiotic therapy with less emphasis on nutritional management. In a randomised clinical trial, we examined the role of an energy-dense diet on the clinical outcome in malnourished children with acute dysentery due to shigellosis. Seventy-five children aged 12–48 months with acute dysentery randomly received either a milk–cereal formula with an energy density of 4960 kJ/l (test group) or a milk–cereal formula with energy of 2480 kJ/l (control group) for 10 d in hospital. In both milk–cereal formulas, protein provided 11 % energy. In addition, the standard hospital diet was offered to all children and all children received an appropriate antibiotic for 5 d. The mean food intakes (g/kg per d) in the test and control groups were: 112 (SE 2·28) AND 116 (se 3·48) (P=0·16) on day 1; 118 (se 2·72) and 107 (se 3·13) (P=0·04) on day 5; 120 (se 2·25) and 100 (se 3·83) (P=0·04) on day 10. The mean energy intakes (kJ/kg per d) in the test and control groups respectively were: 622 (se 13·2) and 315 (se 11·3) (P<0·05) on day 1; 655 (se 15·1) and 311 (se 7·98) (P<0·05) on day 5; 672 (se 14·7) and 294 (se 11·1) (P<0·05) on day 10. The food and energy intakes were mostly from the milk–cereal diet. There was no difference between two groups in resolution of fever, dysenteric (bloody and or mucoid) stools, stool frequency and tenesmus. However, vomiting was more frequently observed among the test-group children during the first 5 d of intervention (67 % v. 41 %, P=0·04). There was an increase in the mean weight-for-age (%) in the test group compared with the control group after the 10 d of dietary intervention (6·2 (se 0·6) v. 2·7 (se 0·4), P<0·01). In addition, resolution of rectal prolapse was better (26 % v. 8 %, P=0·04) in the test group v. control group after 5 d, and 13 % v. 6 %, (P=0·08) after 10 d of dietary intervention. Supplementation with a high-energy diet does not have any adverse effect on clinical course of acute shigellosis and reduces the incidence of rectal prolapse in malnourished children.

Room-temperature single-crystal X-ray studies are recorded for 2- and 4-nitrophenoxide salts of silver(I) and thallium(I), M(2-np) and Tl(4-np) (anhydrous), and Ag(4-np).H2O. Ag(2-np) is monoclinic, P21/c, a 9·012(4), b 5·743(5), c 12·594(5) Å, β 104·34(4)°, Z = 4; conventional R on |F| was 0·042 for No 1378 independent ‘observed’ (I > 3σ(I)) reflections. Tl(2-np) is monoclinic, C2/c, a 27·250(3), b 3·712(1), c 15·147(3) Å, β 114·41(1)°, Z = 8, R 0·025 for No 1346. Ag(4-np).H2O is monoclinic, P21/a, a 5·613(6), b 13·191(7), c 9·844(5) Å, β 92·50(6)°, Z = 4, R 0 ·033 for No 622. Tl(4-np) is tetragonal, I 41/a, a 18·037(8), c 8·979(8) Å, Z = 16, R 0·043 for No 924. An acid salt of the latter, Tl(4-np).(4-npH)3, triclinic, P-1, a 11·861(8), b 11·45(1), c 11· 423(1) Å, α 114·00(6), β 109·78(5), γ 96·87(7)°, Z = 2, R 0·042 for No 3814, is isomorphous with its rubidium analogue. These comprise a novel array of structures: although the structures of the silver(I) complexes are two-dimensional sheets with familiar head-tail connecting ligands, a strong silver-aromatic carbon interaction is found in Ag(2-np) (Ag–C 2·496(5) Å). Tl(2-np) and Tl(4-np) both present unusual forms related to the stair-polymer and cubane adducts found in 1 : 1 coinage metal(I)/halide-unidentate nitrogen base adducts; Tl(2-np) is a double-stranded stair-polymer array, with the phenoxide oxygen atoms incorporated in the stair and the nitro oxygen atoms linking successive thallium atoms. The structure of Tl(4-np) is based on a tetranuclear cubane motif of -4 symmetry, [Tl(O-phenoxide)]4, these being linked into a three-dimensional network by further Tl · · · O-nitro interactions from adjacent units. The structure of silver(I) picrate monohydrate, isomorphous with its sodium counterpart, is also recorded: monoclinic, C 2/m, a 12·818(7), b 20·208(8), c 3· 741(1) Å, β 88·25(3)°, Z = 4, R 0·047 for No 1042, void of any significant Ag · · · C contacts.

Epidemiological studies show that adherence to a Mediterranean diet (MD) increases longevity; however, few studies are restricted to Mediterranean populations or explore the effect of a MD pattern that directly incorporates olive oil. Therefore the relationship between adherence to the MD and mortality was studied within the the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain analysis included 40 622 participants (37·7 % males) aged 29–69 years who were recruited from five Spanish regions in 1992–1996. During a mean follow-up of 13·4 years, 1855 deaths were documented: 913 from cancer, 399 from CVD, 425 from other causes and 118 from unknown causes of death. Risk of all-cause and cause-specific mortality was assessed according to the level of adherence to a relative MD (rMED) score, measured using an 18-unit scale incorporating nine selected dietary components. A high compared with a low rMED score was associated with a significant reduction in mortality from all causes (hazard ratio (HR) 0·79; 95 % CI 0·69, 0·91), from CVD (HR 0·66; 95 % CI 0·49, 0·89), but not from overall cancer (HR 0·92; 95 % CI 0·75, 1·12). A 2-unit increase in rMED score was associated with a 6 % (P < 0·001) decreased risk of all-cause mortality. A high olive oil intake and moderate alcohol consumption contributed most to this association. In this Spanish cohort, following an olive oil-rich MD was related to a significant reduction in all-cause mortality, and reduced the risk of mortality from CVD. These results support the important role that the MD pattern has on reducing mortality in Mediterranean countries.

This paper explores the effect of using regional data for livestock attributes on estimation of greenhouse gas (GHG) emissions for the northern beef industry in Australia, compared with using state/territory-wide values, as currently used in Australia’s national GHG inventory report. Regional GHG emissions associated with beef production are reported for 21 defined agricultural statistical regions within state/territory jurisdictions. A management scenario for reduced emissions that could qualify as an Emissions Reduction Fund (ERF) project was used to illustrate the effect of regional level model parameters on estimated abatement levels. Using regional parameters, instead of state level parameters, for liveweight (LW), LW gain and proportion of cows lactating and an expanded number of livestock classes, gives a 5.2% reduction in estimated emissions (range +12% to –34% across regions). Estimated GHG emissions intensity (emissions per kilogram of LW sold) varied across the regions by up to 2.5-fold, ranging from 10.5 kg CO2-e kg–1 LW sold for Darling Downs, Queensland, through to 25.8 kg CO2-e kg–1 LW sold for the Pindan and North Kimberley, Western Australia. This range was driven by differences in production efficiency, reproduction rate, growth rate and survival. This suggests that some regions in northern Australia are likely to have substantial opportunities for GHG abatement and higher livestock income. However, this must be coupled with the availability of management activities that can be implemented to improve production efficiency; wet season phosphorus (P) supplementation being one such practice. An ERF case study comparison showed that P supplementation of a typical-sized herd produced an estimated reduction of 622 t CO2-e year–1, or 7%, compared with a non-P supplemented herd. However, the different model parameters used by the National Inventory Report and ERF project means that there was an anomaly between the herd emissions for project cattle excised from the national accounts (13 479 t CO2-e year–1) and the baseline herd emissions estimated for the ERF project (8 896 t CO2-e year–1) before P supplementation was implemented. Regionalising livestock model parameters in both ERF projects and the national accounts offers the attraction of being able to more easily and accurately reflect emissions savings from this type of emissions reduction project in Australia’s national GHG accounts.

BackgroundReports of an impaired humoral response after COVID-19 vaccination in patients treated with rituximab (RTX) have raised particular concern for patients with inflammatory rheumatic diseases (IRD) receiving RTX (1). This calls for strategies to enhance a humoral response in RTX-treated patients. At present, there is no data on whether it is best to increase the humoral response with a third vaccine dose (a booster) or with a third and fourth dose (re-vaccination).ObjectivesIn IRD patients treated with RTX, without a detectable humoral response after the first vaccination course (two shots), we aimed to investigate the difference of either a booster vaccine (dose 3) or a new re-vaccination course (dose 3 + 4) on the serological response of the COVID-19 mRNA vaccines.MethodsWe included 84 patients with IRD treated with RTX, all without measurable total SARS-CoV-2 antibodies after a full primary COVID-19 vaccination course (2 doses three weeks apart). All patients were offered a new re-vaccination course with the mRNA vaccine not used primarily (Pfizer/Biontec or Moderna). A small number of patients declined the revaccination, and recieved a booster with the mRNA vaccine used initially. Serum total antibodies were measured before and six weeks after the last dose against recombinant SARS-CoV-2 spike S1 protein (VITROS). In addition, CD19+ B-cells were measured at inclussion.ResultsPatient characteristics are in Table 1. The median age was 64 years; 68% were female with a disease duration of 5 years. Sixty-nine out of 84 were re-vaccinated (3 + 4 dose). Details previous exposure to RTX are given in Table 1. CD19+ B-cells were measurable in 12/81 at inclusion.Table 1.Patient CharacteristicsBooster, n=15Revaccination, n=69Age, years median (IQR)60 (45 - 69)65 (54 - 70)Female47%72%Disease duration, years (IQR)5 (2-8)6(2 - 13) ANCA-vasculitis47 %45 % Rheumatoid Arthritis47 %17 % Poly- Dermatomyositis6 %19 % SLE, Scleroderma, other diagnoses-19 %No DMARD treatment27 %35 %Prednisone33 %46 %Methotrexate40 %16 %Azathioprine7 %12 %Mycophenolate7 %7 %Other20 %9 %Rituximab treatment, (IQR) Months from last RTX to vaccination3.9 (1.3 - 9.3)5.4 (4.2 - 7.3) Number of infusions6 (4 - 8)7 (5 - 12) Cummulativ total dose, gram4 (2.5 - 7.5)6 (3.5 - 10) Total treatment time with RTX, months15 (9 - 54)27 (13 - 63)Patients with measurable CD19+ B-cells in peripheral blood at the time of booster or re-vaccination (positive/total)3/149/67We found a combined seroconversion rate of 33% six weeks after the last shot. There was no statistical difference between the booster (38,5%) and the re-vaccination group (32,3%), p=0.67 (Pearson’s chi-squared). IRD patients with a humoral response in the re-vaccination group had significantly higher levels of total SARS-CoV-2 antibodies (median(IQR) 306(49-464) AU/ml) compared to the booster group (14(4-15) AU/ml) p=0.02, Figure 1A. In multiple logistic regression model, we found that levels of CD19+ B-cells were the only variable able to predict a humoral response, Figure 1B. However, only 39% of the patients with a humoral response to vaccination had measurable CD19+ B-cells before vaccination. We found no effect of age, sex, diagnosis, treatment, and RTX exposure on the chance of seroconversion in multiple logistic regression models when corrected for CD19+ B-cells.Figure 1.ConclusionWe found that re-vaccination (dose 3 + 4) with COVID-19 mRNA vaccines favored a high humoral response in patients with IRD treated with RTX, who did not have a detectable humoral response after the first two vaccine doses, compared to a booster shot (dose 3). A detectable humoral response after re-vaccination was seen in more than half of the patients with no measurable CD19+ B-cells before vaccination. Presence of circulating CD19+ B-cells are a significant predictor of humoral response to mRNA COVID-19 vaccination.References[1]Ammitzbøll et al. ACR Open Rheum. 2021 Sep;3(9):622-628. doi: 10.1002/acr2.11299.AcknowledgementsThe Danish Rheumatism Association - Gigtforeningen for funding the study.Disclosure of InterestsNone declared

White alder (Alnus rhombifolia) is a fast-growing tree native to the western United States and is planted frequently in landscapes. In September 2010, mature leaves of white alder with small, orange-yellow pustules were collected in a commercial nursery in Santa Cruz County, CA. Approximately 25 white alder trees were affected. Collected leaves were sent to the California Department of Food and Agriculture Plant Pest Diagnostics Laboratory. Young uredinial pustules were bullate, with urediniospores emerging from a single pore in the pustule. Spiny cells lined the ostiole. With age, pustules broke open to release more spores. Urediniospores were obovate to oval and measured from 14 to 20 × 27 to 41 μm (17.1 × 32.2 μm average, n = 62). Spores were uniformly echinulate and contained a nearly hyaline cell wall measuring from 1 to 2 μm (1.5 μm average) in thickness. A portion of the 28S ribosomal subunit (GenBank Accession No. KC313888) and the internal transcribed spacer regions (KC313889) were amplified and sequenced from DNA extracted from urediniospores using primers LR6 and rust2inv (1) and ITS1-F and ITS4-B (2), respectively. Our ITS sequence had 99% identity to GenBank accession EF564164, Melampsoridium hiratsukanum. In September 2011, white alder leaves with similar symptoms were collected from a commercial nursery in Santa Barbara County, CA. The spore morphology matched the white alder sample previously collected in Santa Cruz County, CA, in 2010. At that time, pathogenicity assays were conducted on three 1-year-old, 61-cm white alder trees planted in 3.8-liter pots. Six detached leaves with visible rust pustules were rubbed gently onto both the apical and distal side of moistened leaves of the healthy alders. Each infected leaf was used to inoculate a total of 6 to 10 healthy leaves by rubbing two leaves per tree before moving to the next tree. Leaves on three additional white alder trees were rubbed with healthy leaves as controls. Trees were incubated in a dew chamber for 3 days in darkness at 24°C, then placed in a growth chamber at 22°C with a 12-h photoperiod. Twelve days after inoculation, small lesions were visible on a few of the leaf undersides of each inoculated tree. Not all inoculated leaves developed pustules. No lesions developed on the control trees. M. hiratsukanum has been reported in Canada, Europe, and eastern Asia (3). There are no published reports of this rust in the United States, but there is an unpublished specimen from white alder in the USDA Systematic Mycology Herbarium (BPI 028048) collected from California in 1931, which was identified as M. hiratsukanum by G. B. Cummins using morphological criteria. We are unaware if older specimens of this rust exist because we were unable to search other herbaria in the United States. To the best of our knowledge, this rust has been present in California since 1931, but has only recently been found causing disease in nursery plants. There have been no reports of the serious foliar disease symptoms on trees in California wild lands as have been reported in Europe, presumably due to dry summer and fall seasons in white alder's natural habitat. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) M. Gardes and T. D. Bruns. Mol. Ecol. 2:113, 1993. (3) J. Hatula et al. Mycologia 101:622, 2009.