Development of a bead-based multiplex assay for the simultaneous detection of porcine inflammation markers using xMAP technology

Commercially available assays for the simultaneous detection of multiple inflammatory and cardiac markers in porcine blood samples are currently lacking. Therefore, this study was aimed at developing a bead-based, multiplexed flow cytometric assay to simultaneously detect porcine cytokines [interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor alpha], chemokines (IL-8 and monocyte chemotactic protein 1), growth factors [basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and platelet-derived growth factor-bb], and injury markers (cardiac troponin-I) as well as complement activation markers (C5a and sC5b-9). The method was based on the Luminex xMAP technology, resulting in the assembly of a 6- and 11-plex from the respective individual singleplex situation. The assay was evaluated for dynamic range, sensitivity, cross-reactivity, intra-assay and interassay variance, spike recovery, and correlation between multiplex and commercially available enzyme-linked immunosorbent assay as well as the respective singleplex. The limit of detection ranged from 2.5 to 30,000 pg/ml for all analytes (6- and 11-plex assays), except for soluble C5b-9 with a detection range of 2-10,000 ng/ml (11-plex). Typically, very low cross-reactivity (<3% and <1.4% by 11- and 6-plex, respectively) between analytes was found. Intra-assay variances ranged from 4.9 to 7.4% (6-plex) and 5.3 to 12.9% (11-plex). Interassay variances for cytokines were between 8.1 and 28.8% (6-plex) and 10.1 and 26.4% (11-plex). Correlation coefficients with singleplex assays for 6-plex as well as for 11-plex were high, ranging from 0.988 to 0.997 and 0.913 to 0.999, respectively. In this study, a bead-based porcine 11-plex and 6-plex assay with a good assay sensitivity, broad dynamic range, and low intra-assay variance and cross-reactivity was established. These assays therefore represent a new, useful tool for the analysis of samples generated from experiments with pigs.

The Think Manager-Think Male Stereotype - Malleable or Stable?

Purpose Stereotypes about leadership still represent a potent barrier to women’s advancement to leadership roles. Successful leaders are perceived to possess predominately agentic traits (e.g., assertive, dominant) that are more similar to those ascribed to men than women. This perceived incongruity of people’s beliefs about leaders and women underlies prejudice against women leaders (Eagly & Karau, 2002). Thus, an important question is whether such stereotypical beliefs about the traits of leaders, men, and women incorporate change or stability over time. Design/Methodology To examine this question, 235 Irish business students (113 men, 122 women) rated a target group’s characteristics (men, women, middle managers) as of a specific time (50 years ago, present, 50 years into the future) on gender‐stereotypical traits. Results Following Schein’s (1973) approach, intraclass correlation coefficients estimated the extent to which the stereotype of managers was similar to that of men or women. The results showed a large, significant correlation between the stereotypes about men and managers within each time condition and overall. In contrast, the women‐manager correlation was negative and nonsignificant overall. However, this negative correlation weakened from the past to the present and became positive and marginally significant for the future. Research/Practical Implications Altogether the results suggest that people perceive stereotypes about leaders to be more similar to men than to women. These perceptions may continue to function as impediments to women leaders’ advancement despite the trend over time toward femalemanager similarity. Originality/Value To our knowledge this is the first study to systematically test perceptions of change in the think manager‐think male stereotype overtime.

Variability between laboratories performing coagulation tests with identical platforms: a nationwide evaluation study.

BACKGROUND While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.

Short-term Functional and Patient Outcome of the Bi-cruciate Stabilized Total Knee Replacement: Prospective Consecutive Case-series

Background: Total knee replacement is the gold standard treatment for patients suffering from advanced symptomatic knee osteoarthritis. The main goals of knee prosthetics are pain reduction and restoration of knee motion. The new prostheses on the market such as the bi-cruciate stabilized Journey knee implant, promise a reconstruction of total physiological function of the knee with physiological range of motion and therefore high patient satisfaction. Purpose: The aim of this study was to analyze the patient-based Knee Injury and Osteoarthritis Outcome Score (KOOS) outcome after total knee replacement with new physiological bi-cruciate stabilized Journey knee prosthesis. Study Design: Prospective, consecutive case-series. Patients: Ninety nine patients, who received bi-cruciate stabilized Journey total knee prosthesis between January 1st 2006 and May 31st 2012, were included in the study. A single surgeon operated all patients. There were 61.1% females and the overall average age was 68 years (range 41-83 years). Left knee was replaced in 55.6%. Methods: The patients filled in KOO’s questionnaire pre- and 1 year postoperative. Range of motion (ROM) was studied preoperatively and at 1-year follow-ups. The pre- and postoperative KOOS subscores and ROM were compared using the Wilcoxon signed rank test. Results: There are significant improvements of all KOOS subscores. Ninety percent of patients have reached the minimum clinically relevant 10 points in symptoms, 94.5% in pain, 94.5% in activities of daily living, 84.9% in sport and recreation, and 90% in knee related quality of life. Postoperative, the average passive ROM was 131° (range 110-145°) and the average active ROM 122° (range 105-135°). The highest correlation coefficients ROM and the KOOS were observed for the activity and pain subscores. Very low or no correlation was seen for the sport subscore. Conclusions: Bi-cruciate stabilized knee prosthetic offers a solid outcome 1 year postoperative based on the results measured with the KOOS evaluation questionnaire. The Patients showed a generalized improvement in all domains measured in the KOOS of minimally 35, and up to over 52 points, what can be described as statistically significant. Patients described the level of functionality close to double compared to the preoperative status.

Validation of middle-atmospheric campaign-based water vapour measured by the ground-based microwave radiometer MIAWARA-C

Middle atmospheric water vapour can be used as a tracer for dynamical processes. It is mainly measured by satellite instruments and ground-based microwave radiometers. Ground-based instruments capable of measuring middle-atmospheric water vapour are sparse but valuable as they complement satellite measurements, are relatively easy to maintain and have a long lifetime. MIAWARA-C is a ground-based microwave radiometer for middle-atmospheric water vapour designed for use on measurement campaigns for both atmospheric case studies and instrument intercomparisons. MIAWARA-C's retrieval version 1.1 (v1.1) is set up in a such way as to provide a consistent data set even if the instrument is operated from different locations on a campaign basis. The sensitive altitude range for v1.1 extends from 4 hPa (37 km) to 0.017 hPa (75 km). For v1.1 the estimated systematic error is approximately 10% for all altitudes. At lower altitudes it is dominated by uncertainties in the calibration, with altitude the influence of spectroscopic and temperature uncertainties increases. The estimated random error increases with altitude from 5 to 25%. MIAWARA-C measures two polarisations of the incident radiation in separate receiver channels, and can therefore provide two measurements of the same air mass with independent instrumental noise. The standard deviation of the difference between the profiles obtained from the two polarisations is in excellent agreement with the estimated random measurement error of v1.1. In this paper, the quality of v1.1 data is assessed for measurements obtained at two different locations: (1) a total of 25 months of measurements in the Arctic (Sodankylä, 67.37° N, 26.63° E) and (2) nine months of measurements at mid-latitudes (Zimmerwald, 46.88° N, 7.46° E). For both locations MIAWARA-C's profiles are compared to measurements from the satellite experiments Aura MLS and MIPAS. In addition, comparisons to ACE-FTS and SOFIE are presented for the Arctic and to the ground-based radiometer MIAWARA for the mid-latitude campaigns. In general, all intercomparisons show high correlation coefficients, confirming the ability of MIAWARA-C to monitor temporal variations of the order of days. The biases are generally below 13% and within the estimated systematic uncertainty of MIAWARA-C. No consistent wet or dry bias is identified for MIAWARA-C. In addition, comparisons to the reference instruments indicate the estimated random error of v1.1 to be a realistic measure of the random variation on the retrieved profile between 45 and 70 km.

A quality of life subscale for terminally ill cancer patients

A subscale was developed to assess the quality of life of cancer patients with a life expectancy of six months or less. Phase I of this study identified the major concerns of 74 terminally ill cancer patients (19 with breast cancer, 19 with lung cancer, 18 with colorectal cancer, 9 with renal cell cancer, 9 with prostate cancer), 39 family caregivers, and 20 health care professionals. Patients interviewed were being treated at the University of Texas M. D. Anderson Cancer Center or at the Hospice at the Texas Medical Center in Houston. In Phase II, 120 patients (30 with breast cancer, 30 with lung cancer, 30 with colorectal cancer, 15 with prostate cancer, and 15 with renal cell cancer) rated the importance of these concerns for quality of life. Items retained for the subscale were rated as "extremely important" or "very important" by at least 60% of the sample and were reported as being applicable by at least two-thirds of the sample. The 61 concerns that were identified were formatted as a questionnaire for Phase III. In Phase III, 356 patients (89 with breast cancer, 88 with lung cancer, 88 with colorectal cancer, 44 with prostate cancer, and 47 with renal cell cancer) were interviewed to determine the subscale's reliability and sensitivity to change in clinical status. Both factor analysis and item response theory supported the inclusion of the same 35 items for the subscale. Internal consistency reliability was moderate to high for the subscale's domains: spiritual (0.87), existential (0.76), medical care (0.68), symptoms (0.67), social/family (0.66), and emotional (0.61). Test-retest correlation coefficients also were high for the domains: social/family (0.86), emotional (0.83), medical care (0.83), spiritual (0.75), existential (0.75), and symptoms (0.81).^ In addition, concurrent validity was supported by the high correlation between the subscale's symptom domain and symptom items from the European Organization for Research and Treatment of Cancer (EORTC) scale (r = 0.74). Patients' functional status was assessed with the Eastern Cooperative Oncology Group (ECOG) Performance status rating. When ECOG categories were compared to subscale domains, patients who scored lower in functional status had lower scores in the spiritual, existential, social/family, and emotional domains. Patients who scored lower in physical well-being had higher scores in the symptom domain. Patient scores in the medical care domain were similar for each ECOG category. The results of this study support the subscale's use in assessing quality of life and the outcomes of palliative treatment for cancer patients in their last six months of life. ^

HUMAN PROPHASE CHROMOSOME UNIQUE BAND SEQUENCES; DEFINITION, CHARACTERIZATION, AND APPLICATION (CYTOGENETICS, IMAGE PROCESSING)

Extensive experience with the analysis of human prophase chromosomes and studies into the complexity of prophase GTG-banding patterns have suggested that at least some prophase chromosomal segments can be accurately identified and characterized independently of the morphology of the chromosome as a whole. In this dissertation the feasibility of identifying and analyzing specified prophase chromosome segments was thus investigated as an alternative approach to prophase chromosome analysis based on whole chromosome recognition. Through the use of prophase idiograms at the 850-band-stage (FRANCKE, 1981) and a comparison system based on the calculation of cross-correlation coefficients between idiogram profiles, we have demonstrated that it is possible to divide the 24 human prophase idiograms into a set of 94 unique band sequences. Each unique band sequence has a banding pattern that is recognizable and distinct from any other non-homologous chromosome portion.^ Using chromosomes 11p and 16 thru 22 to demonstrate unique band sequence integrity at the chromosome level, we found that prophase chromosome banding pattern variation can be compensated for and that a set of unique band sequences very similar to those at the idiogram level can be identified on actual chromosomes.^ The use of a unique band sequence approach in prophase chromosome analysis is expected to increase efficiency and sensitivity through more effective use of available banding information. The use of a unique band sequence approach to prophase chromosome analysis is discussed both at the routine level by cytogeneticists and at an image processing level with a semi-automated approach to prophase chromosome analysis. ^

Scaling relations between trabecular bone volume fraction and microstructure at different skeletal sites

In this study, we investigated the scaling relations between trabecular bone volume fraction (BV/TV) and parameters of the trabecular microstructure at different skeletal sites. Cylindrical bone samples with a diameter of 8mm were harvested from different skeletal sites of 154 human donors in vitro: 87 from the distal radius, 59/69 from the thoracic/lumbar spine, 51 from the femoral neck, and 83 from the greater trochanter. μCT images were obtained with an isotropic spatial resolution of 26μm. BV/TV and trabecular microstructure parameters (TbN, TbTh, TbSp, scaling indices (< > and σ of α and αz), and Minkowski Functionals (Surface, Curvature, Euler)) were computed for each sample. The regression coefficient β was determined for each skeletal site as the slope of a linear fit in the double-logarithmic representations of the correlations of BV/TV versus the respective microstructure parameter. Statistically significant correlation coefficients ranging from r=0.36 to r=0.97 were observed for BV/TV versus microstructure parameters, except for Curvature and Euler. The regression coefficients β were 0.19 to 0.23 (TbN), 0.21 to 0.30 (TbTh), −0.28 to −0.24 (TbSp), 0.58 to 0.71 (Surface) and 0.12 to 0.16 (<α>), 0.07 to 0.11 (<αz>), −0.44 to −0.30 (σ(α)), and −0.39 to −0.14 (σ(αz)) at the different skeletal sites. The 95% confidence intervals of β overlapped for almost all microstructure parameters at the different skeletal sites. The scaling relations were independent of vertebral fracture status and similar for subjects aged 60–69, 70–79, and >79years. In conclusion, the bone volume fraction–microstructure scaling relations showed a rather universal character.

Cardiothoracic ratio in postmortem computed tomography: reliability and threshold for the diagnosis of cardiomegaly

The aim of this study was to evaluate the reliability of the cardiothoracic ratio (CTR) in postmortem computed tomography (PMCT) and to assess a CTR threshold for the diagnosis of cardiomegaly based on the weight of the heart at autopsy. PMCT data of 170 deceased human adults were retrospectively evaluated by two blinded radiologists. The CTR was measured on axial computed tomography images and the actual cardiac weight was weighed at autopsy. Inter-rater reliability, sensitivity, and specificity were calculated. Receiver operating characteristic curves were calculated to assess enlarged heart weight by CTR. The autopsy definition of cardiomegaly was based on normal values of the Zeek method (within a range of both, one or two SD) and the Smith method (within the given range). Intra-class correlation coefficients demonstrated excellent agreements (0.983) regarding CTR measurements. In 105/170 (62 %) cases the CTR in PMCT was >0.5, indicating enlarged heart weight, according to clinical references. The mean heart weight measured in autopsy was 405 ± 105 g. As a result, 114/170 (67 %) cases were interpreted as having enlarged heart weights according to the normal values of Zeek within one SD, while 97/170 (57 %) were within two SD. 100/170 (59 %) were assessed as enlarged according to Smith's normal values. The sensitivity/specificity of the 0.5 cut-off of the CTR for the diagnosis of enlarged heart weight was 78/71 % (Zeek one SD), 74/55 % (Zeek two SD), and 76/59 % (Smith), respectively. The discriminative power between normal heart weight and cardiomegaly was 79, 73, and 74 % for the Zeek (1SD/2SD) and Smith methods respectively. Changing the CTR threshold to 0.57 resulted in a minimum specificity of 95 % for all three definitions of cardiomegaly. With a CTR threshold of 0.57, cardiomegaly can be identified with a very high specificity. This may be useful if PMCT is used by forensic pathologists as a screening tool for medico-legal autopsies.

Ice Layers as an Indicator of Summer Warmth and Atmospheric Blocking in Alaska

Samples were collected from a snow pit and shallow urn core near Kahiltna Pass (2970 m a.s.l.), Denali National Park, Alaska, USA, in May 2008. The record spans autumn 2003 to spring 2008 and reveals clusters of ice layers interpreted as summertime intervals of above-freezing temperatures. High correlation coefficients (0.75-1.00) between annual ice-layer thickness and regional summertime station temperatures for 4 years (n=4) indicate ice-layer thickness is a good proxy for mean and extreme summertime temperatures across Alaska, at least over the short period of record. A Rex-block (aka high-over-low) pattern, a downstream trough over Hudson Bay, Canada, and an upstream trough over eastern Siberia occurred during the three melting events that lasted at least 2 weeks. About half of all shorter melting events were associated with a cut-off low traversing the Gulf of Alaska. We hypothesize that a surface-to-bedrock core extracted from this location would provide a high-quality record of summer temperature and atmospheric blocking variability for the last several hundred years.

Diurnal variations in middle-atmospheric water vapor by ground-based microwave radiometry

Abstract. In this paper, we compare the diurnal variations in middle-atmospheric water vapor as measured by two ground-based microwave radiometers in the Alpine region near Bern, Switzerland. The observational data set is also compared to data from the chemistry–climate model WACCM. Due to the small diurnal variations of usually less than 1%, averages over extended time periods are required. Therefore, two time periods of five months each, December to April and June to October, were taken for the comparison. The diurnal variations from the observational data agree well with each other in amplitude and phase. The linear correlation coefficients range from 0.8 in the upper stratosphere to 0.5 in the upper mesosphere. The observed diurnal variability is significant at all pressure levels within the sensitivity of the instruments. Comparing our observations with WACCM, we find that the agreement of the phase of the diurnal cycle between observations and model is better from December to April than from June to October. The amplitudes of the diurnal variations for both time periods increase with altitude in WACCM, but remain approximately constant at 0.05 ppm in the observations. The WACCM data are used to separate the processes that lead to diurnal variations in middle-atmospheric water vapor above Bern. The dominating processes were found to be meridional advection below 0.1 hPa, vertical advection between 0.1 and 0.02 hPa and (photo-)chemistry above 0.02 hPa. The contribution of zonal advection is small. The highest diurnal variations in water vapor as seen in the WACCM data are found in the mesopause region during the time period from June to October with diurnal amplitudes of 0.2 ppm (approximately 5% in relative units).

Multi-modal glioblastoma segmentation: man versus machine

BACKGROUND AND PURPOSE Reproducible segmentation of brain tumors on magnetic resonance images is an important clinical need. This study was designed to evaluate the reliability of a novel fully automated segmentation tool for brain tumor image analysis in comparison to manually defined tumor segmentations. METHODS We prospectively evaluated preoperative MR Images from 25 glioblastoma patients. Two independent expert raters performed manual segmentations. Automatic segmentations were performed using the Brain Tumor Image Analysis software (BraTumIA). In order to study the different tumor compartments, the complete tumor volume TV (enhancing part plus non-enhancing part plus necrotic core of the tumor), the TV+ (TV plus edema) and the contrast enhancing tumor volume CETV were identified. We quantified the overlap between manual and automated segmentation by calculation of diameter measurements as well as the Dice coefficients, the positive predictive values, sensitivity, relative volume error and absolute volume error. RESULTS Comparison of automated versus manual extraction of 2-dimensional diameter measurements showed no significant difference (p = 0.29). Comparison of automated versus manual segmentation of volumetric segmentations showed significant differences for TV+ and TV (p<0.05) but no significant differences for CETV (p>0.05) with regard to the Dice overlap coefficients. Spearman's rank correlation coefficients (ρ) of TV+, TV and CETV showed highly significant correlations between automatic and manual segmentations. Tumor localization did not influence the accuracy of segmentation. CONCLUSIONS In summary, we demonstrated that BraTumIA supports radiologists and clinicians by providing accurate measures of cross-sectional diameter-based tumor extensions. The automated volume measurements were comparable to manual tumor delineation for CETV tumor volumes, and outperformed inter-rater variability for overlap and sensitivity.

A Comparison of Complications in 400 Patients After Native Nail Versus Silicone Nail Splints for Fingernail Splinting After Injuries

BACKGROUND The fingertip is the most commonly injured part of the hand and is an important aesthetic part of the hand. METHODS In this retrospective study we analyzed data from 700 patients operated on between 1997 and 2008 for complications after nail splinting with native nail or silicone nail. Inclusion criteria were patients living in Bern/Berner Land, complete documentation, same surgical team, standard antibiotics, acute trauma, no nail bed transplantation, and no systemic diseases. Groups were analyzed for differences in age, gender, cause and extension of trauma, bony injury and extent, infection, infectious agent, and nail deformities. Statistical analysis was done using the χ (2) test, Fisher's exact test, and Pearson correlation coefficients. RESULTS A total of 401 patients, with a median age of 39.5 years, were included. There were more men with injured nails. Two hundred forty native nails and 161 silicone splints were used. There were 344 compression injuries, 44 amputations, and 13 avulsion injuries. Forty-three patients had an infection, with gram-positive bacteria (Staphylococcus aureus) causing most infections. A total of 157 nail dystrophies were observed, split nails most often. The native nail splint group showed significantly (p < 0.015) fewer nail deformities than the silicone nail splint group; otherwise, there were no statistical differences. However, there were twice as many infections in the silicone nail group. CONCLUSION It seems to be advantageous to use the native nail for splinting after trauma, when possible. In case of a destroyed and unusable nail plate, a nail substitute has to be used.

Multiple tree-ring proxies (earlywood width, latewood width and δ13C) from pedunculate oak (Quercus robur L.), Hungary

The aim of this study was to analyse the effects of climatic factors (i.e. monthly mean temperature and total precipitation) on radial growth (earlywood width, latewood width, and total ringwidth) and on latewood stable carbon isotope composition in a pedunculate oak (Quercus robur L) stand in northeastern Hungary. Earlywood widths showed the weakest common variance and lack of statistically significant relationship to monthly precipitation and temperature. Latewood width showed the strongest common chronological signal. Correlation analysis with the monthly climate series pointed out the strongest positive/negative correlation with June precipitation for latewood width/stable carbon isotope ratio. These parameters shared the strongest climatic response also for seasonal scale since the highest correlation coefficients, 0.49 and -0.62 for latewood width and stable carbon isotope ratio, respectively, were obtained for both with a 10-month precipitation total (from previous November to current August of the growing season). A combined parameter, derived as difference between latewood width and stable carbon isotope indices showed improved statistical relationship compared to the hydroclimatic calibration target both for local and regional spatial scales. Spatial correlation analysis indicated that the hydroclimatic signal encoded in these moisture sensitive tree-ring parameters from Bakta Forest is expected to be representative for the northeastern Carpathians and for the large part of the Great Hungarian Plain. In addition, the hydroclimatic signal of latewood width chronology was compared to three independent records. Results showed that neither the strength nor the rank of the similarity of the local hydroclimate signals were stable throughout the past two centuries. Future palaeo(hydro)climatological efforts targeting the Carpathian(-Balkan) region are recommended to track carefully the spatial domains for which a given, local, proxy-derived hydroclimate reconstruction might provide useful information.

Summer temperature in the eastern part of southern South America: its variability in the twentieth century and a teleconnection with Oceania

The 1907–2001 summer-to-summer surface air temperature variability in the eastern part of southern South America (SSA, partly including Patagonia) is analysed. Based on records from instruments located next to the Atlantic Ocean (36°S–55°S), we define indices for the interannual and interdecadal timescales. The main interdecadal mode reflects the late-1970s cold-to-warm climate shift in the region and a warm-to-cold transition during early 1930s. Although it has been in phase with the Pacific Decadal Oscillation (PDO) index since the 1960s, they diverged in the preceding decades. The main interannual variability index exhibits high spectral power at ~3.4 years and is representative of temperature variability in a broad area in the southern half of the continent. Eleven-years running correlation coefficients between this index and December-to-February (DJF) Niño3.4 show significant decadal fluctuations, out-of-phase with the running correlation with a DJF index of the Southern Annular Mode. The main interannual variability index is associated with a barotropic wavetrain-like pattern extending over the South Pacific from Oceania to SSA. During warm (cold) summers in SSA, significant anticyclonic (cyclonic) anomalies tend to predominate over eastern Australia, to the north of the Ross Sea, and to the east of SSA, whereas anomalous cyclonic (anticyclonic) circulation is observed over New Zealand and west of SSA. This teleconnection links warm (cold) SSA anomalies with dry (wet) summers in eastern Australia. The covariability seems to be influenced by the characteristics of tropical forcing; indeed, a disruption has been observed since late 1970s, presumably due to the PDO warm phase.