Neighbourhood species richness and drought-tolerance traits modulate tree growth and δ13 C responses to drought.

Mixed-species forests are promoted as a forest management strategy for climate change adaptation, but whether they are more resistant to drought than monospecific forests remains contested. In particular, the trait-based mechanisms driving the role of tree diversity under drought remain elusive. Using tree cores from a large-scale biodiversity experiment, we investigated tree growth and physiological stress responses (i.e. increase in wood carbon isotopic ratio; δ13 C) to changes in climate-induced water availability (wet to dry years) along gradients in neighbourhood tree species richness and drought-tolerance traits. We hypothesized that neighbourhood species richness increases growth and decreases δ13 C and that these relationships are modulated by the abiotic (i.e. climatic conditions) and the biotic context. We characterised the biotic context using drought-tolerance traits of focal trees and their neighbours. These traits are related to cavitation resistance versus resource acquisition and stomatal control. Tree growth increased with neighbourhood species richness. However, we did not observe a universal relief of water stress in species-rich neighbourhoods. The effects of neighbourhood species richness and climate on growth and δ13 C were modulated by the traits of focal trees and the traits of their neighbours. At either end of each drought-tolerance gradient, species responded in opposing directions during dry and wet years. We show that species' drought-tolerance traits can explain the strength and nature of biodiversity-ecosystem functioning relationships in experimental tree communities experiencing drought. Mixing tree species can increase growth but may not universally relieve drought stress.

Temperature stability of static and dynamic properties of 1.55 µm quantum dot lasers.

Static and dynamic properties of InP-based 1.55 µm quantum dot (QD) lasers were investigated. Due to the reduced size inhomogeneity and a high dot density of the newest generation of 1.55 µm QD gain materials, ridge waveguide lasers (RWG) exhibit improved temperature stability and record-high modulation characteristics. Detailed results are shown for the temperature dependence of static properties including threshold current, voltage-current characteristics, external differential efficiency and emission wavelength. Similarly, small and large signal modulations were found to have only minor dependences on temperature. Moreover, we show the impact of the active region design and the cavity length on the temperature stability. Measurements were performed in pulsed and continuous wave operation. High characteristic temperatures for the threshold current were obtained with T0 values of 144 K (15 - 60 °C), 101 K (60 - 110 °C) and 70 K up to 180 °C for a 900-µm-long RWG laser comprising 8 QD layers. The slope efficiency in these lasers is nearly independent of temperature showing a T1 value of more than 900 K up to 110 °C. Due to the high modal gain, lasers with a cavity length of 340 µm reached new record modulation bandwidths of 17.5 GHz at 20 °C and 9 GHz at 80 °C, respectively. These lasers were modulated at 26 GBit/s in the non-return to zero format at 80 °C and at 25 GBaud using a four-level pulse amplitude format at 21 °C.

Factors correlating with lymph node metastases in patients with T1 breast cancer.

BACKGROUND: Identification of reliable predictors of axillary metastases (ALNM) may be useful in selecting appropriate management for patients with T1-size breast cancer. This study was undertaken to determine the degree of correlation between ALNM and several variables, including age, race, menopausal status, palpability, tumor size, positive margin on initial excision, histology, grade, lymphatic invasion (LI), estrogen receptor status (ER), progesterone receptor status, S-phase, and ploidy. METHODS: Data from 1416 patients with T1 breast cancers treated at Columbia-Presbyterian Medical Center between 1989 and 1998 was reviewed. Patients with multifocal tumors were excluded. RESULTS: Mean patient age was 57.5 years (SD = 12.0); 65% of the patients were postmenopausal. One hundred thirty-one patients with Tla (< or =0.5 cm), 435 with T1b (0.6-1.0 cm), and 850 patients with T1c (1.1-2.0 cm) lesions were studied. The overall rate of ALNM was 23%. AM was identified in 11% of T1a, 15% of T1b, and 29% of T1c patients. Statistically significant factors from univariate analysis were age, palpability, skin changes, tumor size, LI, histology, grade, ER status, and positive margin on initial excision. CONCLUSIONS: Axillary staging by either sentinel lymph node biopsy or level I/II axillary dissection is indicated for most T1 breast cancer patients. Omission of axillary staging can be considered for highly selected patients with T1a cancers.

Estimating the effect of an intensive surveillance program on stage of breast carcinoma at diagnosis: a propensity score analysis.

BACKGROUND: The authors used propensity score adjustment to investigate the impact of intensive screening on stage of breast carcinoma at diagnosis in women who were at elevated risk for breast carcinoma. METHODS: The authors compared 58 women participating in a surveillance program at the Columbia Presbyterian Medical Center of New York Presbyterian Hospital who developed breast carcinoma with 3022 nonparticipating breast carcinoma patients. A propensity score was constructed for each woman by using important background covariates, and multivariable regression modeling was used to estimate the association of program membership with disease stage after adjusting for the propensity score. RESULTS: Before propensity score adjustment, nine baseline covariates significantly differed between the two groups (number of pregnancies, number of births, age at first delivery, race, how the tumor was discovered, history of prior breast disease, breast carcinoma in mother, breast carcinoma in maternal aunt, and breast carcinoma in sister), and there was a significant difference in stage at diagnosis. After adjustment, no significant differences remained. Program participants were more likely to have lower stage tumors at diagnosis than nonparticipants, but this association did not reach statistical significance (odds ratio, 1.52; 95% confidence interval, 0.94--2.46). CONCLUSIONS: Propensity score methods can remove bias in treatment comparisons in observational studies. An intensive surveillance program at a major cancer center may have had some effect on improving stage at diagnosis, but this effect was not statistically significant.

The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer.

A number of polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants that cause mammary cancer experimentally. We investigated whether exposure and susceptibility to PAH, as measured by PAH-DNA adducts in breast tissue, are associated with human breast cancer. We carried out a hospital-based case-control study using immunohistochemical methods to analyze PAH-DNA adducts in tumor and nontumor breast tissue from cases and benign breast tissue from controls. The subjects were white, African-American and Latina women without prior cancer or treatment, including 119 women with breast cancer and 108 with benign breast disease without atypia. PAH-DNA adducts measured in breast tumor tissue of 100 cases and in normal tissue from 105 controls were significantly associated with breast cancer (OR=4.43, 96% CI 1.09-18.01) after controlling for known breast cancer risk factors and current active and passive smoking, and dietary PAH. There was substantial interindividual (17-fold) variability in adducts overall, with 27% of cases and 13% of controls having elevated adducts. The odds ratio for elevated adducts in tumor tissue compared with control tissue was 2.56 (1. 05-6.24), after controlling for potential confounders. Adduct levels in tumor tissue did not vary by stage or tumor size. Among 86 cases with paired tumor and nontumor tissue, adducts levels in these two tissues were highly correlated (r=0.56, P<0.001). However, the corresponding associations between case-control status and adducts measured in nontumor tissue from 90 cases and in normal tissue from 105 controls were positive but not statistically significant. Overall, neither active nor passive smoking, or dietary PAH were significantly associated with PAH-DNA adducts or breast cancer case-control status. These results suggest that genetic damage reflecting individual exposure and susceptibility to PAH may play a role in breast cancer; but more research is needed to determine whether the findings are relevant to causation or progression of breast cancer.

Short-term outcome of chronic immunosuppression on the development of breast lesions in premenopausal heart and lung transplant patients.

The risk of development of breast lesions in patients on chronic immunosuppression is unknown. In order to assess this risk, a retrospective review was performed of the records of 87 women between the ages of 12 and 47 years who received thoracic organ transplant from 1987 to 1996 at our institution. Inclusion criteria consisted of patients who were premenopausal, had no previous history of breast disease, and survived for at least 1 year posttransplantation. All patients were on a triple immunosuppressive regimen consisting of cyclosporine, steroids, and azathioprine. Mean follow-up was 4 +/- 1.2 years with a range of 1-6 years. During this period, 21 patients (24%) with a mean age of 38 +/- 10 years had screening or diagnostic mammography. The remainder of patients with a mean age of 24 +/- 9 years were followed clinically. Overall, 10 patients (11%) developed a total of 17 palpable, solid lesions at 33 to 72 months posttransplantation. Fifteen of these lesions were surgically excised. Five of the patients had multiple lesions. Pathological examination of the specimens revealed fibroadenoma in nine, fibrocystic disease in four, low grade phylloides tumor in one, and T-cell lymphoma in one case. None of the patients have developed primary breast cancer during follow-up. In conclusion, short-term immunosuppression does not increase the risk of the development of benign breast lesions in young women after thoracic organ transplantation, but rather the distribution of benign lesions is similar in an age-matched population. There were several cases of multiple fibroadenomas in the transplant population, but mammography revealed no malignant disease in this age group and does not need to be utilized in this population beyond what is considered standard for immunocompetent patients. The long-term effect ofimmunosuppressive therapy on the developmentof breast cancer in this group remains to be defined.

Organochlorine compounds (DDE and PCB) in plasma and breast cyst fluid of women with benign breast disease.

The organochlorines, dichloro-diphenyl-trichloroethane and polychlorinated biphenyl (PCB) are pervasive environmental contaminants. Results from previous studies have been conflicting regarding the relationship between the internal dose of these organochlorine residues and breast cancer risk. To determine whether these compounds are present in breast cyst fluids and whether cyst fluid and plasma concentrations are correlated, we analyzed organochlorines in paired cyst fluid and plasma samples from 24 subjects using gas chromatography and electron capture detection. All but one of the women had a history of multiple cysts, suggesting that they were at elevated risk for future breast cancer. DDE (a metabolite of dichloro-diphenyl-trichloroethane) was present in 22 of the cyst samples and PCB was detected in 19 of the cyst samples. Organochlorine levels were more concentrated in the plasma than in breast cyst fluids. Levels of DDE in plasma were significantly correlated with those in cyst fluid (r = 0.73; P < 0.001); in contrast to PCB levels in cyst and plasma (r = 0.37; P = 0.12). Congener specific analysis of the PCBs showed that some individual congeners were preferentially excluded from or concentrated in the cyst fluid. To our knowledge, this study is the first to demonstrate that PCB and DDE are present in cyst fluids and thus in contact with the ductal epithelium of the breast. These results support the use of plasma DDE as a proxy for DDE in the target tissue in research on the role of environmental factors in breast cancer.

Immediate breast reconstruction in patients with locally advanced disease.

Immediate breast reconstruction for patients with early-stage disease is well established. This study evaluates a consecutive series of 22 patients with locally advanced disease (stage IIB or III) who underwent mastectomy and immediate breast reconstruction. All patients received several cycles of neoadjuvant chemotherapy (average, 3.5 cycles) followed by completion of chemotherapy beginning approximately 3 weeks following surgery. The perioperative morbidity was 14% and no patient suffered a delay in the resumption of chemotherapy. Patients have been particularly grateful about being offered reconstruction in this setting. Our preliminary results with this technique have been encouraging and further study is warranted.

The relationship of urinary thromboxane excretion to cyclosporine nephrotoxicity.

Alterations in renal prostaglandin production have recently been postulated to modulate the decrease in renal blood flow associated with cyclosporine nephrotoxicity. In particular, increases in renal production of the potent vasoconstrictor thromboxane A2 have been implicated in the pathogenesis of this disorder. The present study was undertaken to explore the relationship between alterations in urinary thromboxane B2 excretion (UTxB2V) and CsA nephrotoxicity in two rat models. Male Sprague-Dawley (SD) rats were treated for 14 days with CsA 50 mg/kg/day (n = 8) or olive oil (C) (n = 9) by gavage. Creatinine clearance (Ccr), urine flow (V), and urinary excretion rates of sodium, N-acetyl-beta-D-glucosaminidase (NAG), glucose, and TxB2 were determined before and after treatment. A similar study was conducted using Fischer rats (CsA: n = 10, C: n = 13). In Fischer rats, CsA caused a 35% decrease in Ccr (P = 0.01), a 33% decrease in sodium excretion (P = 0.02), and a greater than 2-fold increase in NAG excretion (P = 0.03), while V, glucose excretion, and UTxB2V did not change. Although similar changes in sodium and NAG excretion were seen after CsA administration in SD rats, Ccr was not affected. Additional findings in SD rats included a 3-fold increase in V (P less than 0.01), a 24-fold increase in glucose excretion (P = 0.03), and a 5-fold increase in UTxB2V (P = 0.04). Thus, Fischer rats developed CsA nephrotoxicity in the absence of increased UTxB2V. In contrast, SD rats failed to develop nephrotoxicity despite a marked increase in UTxB2V. We conclude that changes in renal TxA2 production are unrelated to the development of CsA nephrotoxicity.

Renal vascular reactivity in the bile duct-ligated rat.

The renal dysfunction associated with liver disease appears to be caused by decreased renal perfusion. Altered renal vascular reactivity (RVR) may contribute to the development of decreased renal blood flow. This study was undertaken to assess the effect of bile duct ligation (BDL) on RVR to norepinephrine and angiotensin II in the rat and to evaluate the role of prostaglandins in the modulation of altered RVR. Male Sprague-Dawley rats underwent either sham operation (SO) or BDL. Four days later, isolated kidney perfusions were established. Dose-response curves to norepinephrine (SO, n = 9; BDL, n = 10) and angiotensin II (SO, n = 7; BDL, n = 9) were obtained. The perfusate was modified to contain indomethacin, 10(-6) mol/L, and dose-response curves to norepinephrine (SO, n = 10; BDL, n = 8) and angiotensin II (SO, n = 4; BDL, n = 8) were obtained as well. Baseline resistances did not differ between any of the groups. RVR to norepinephrine did not appear to be altered by BDL; however, increased RVR to norepinephrine was unmasked by inhibition of prostaglandin synthesis. BDL did not affect the RVR to angiotensin II with or without indomethacin. BDL is associated with an increase in renal vascular sensitivity to norepinephrine, which is balanced by a compensatory increase in renal prostaglandin activity in response to norepinephrine stimulation. These findings are consistent with theories that decreased renal perfusion associated with liver disease may be mediated by catecholamines.