Detection of photoacoustic transients originating from microstructures in optically diffuse media such as biological tissue

The generation and detection of broadband photoacoustic (PA) transients may be used for on-axis monitoring or for imaging of optically different structures in the interior of diffuse bodies such as biological tissue. Various piezoelectric sensors are characterized and compared in terms of sensitivity, depth response, and directivity with respect to spherical broadband acoustic pulses. The influence on the sensor output of acoustic interference and refraction of the PA transients at the sample-sensor interface is discussed. Ring detectors are suitable for deep on-axis detection thanks to their strong directional sensitivity, and small disk sensors are most suited for 3-D imaging of microstructures such as the (micro)vascular system. Voltage and charge preamplification schemes are compared in terms of the signal-to-noise ratio (SNR). In all cases, the preamplifier noise turns out to be the limiting factor for the sensitivity. Based on experimental data, for several sensor types and optical wavelengths, the theoretical detectability of PA signals generated by blood-like absorbers in biological tissue is discussed     

Ergonomics and sustainability: towards an embrace of complexity and emergence

Technology offers a promising route to a sustainable future, and ergonomics can serve a vital role. The argument of this article is that the lasting success of sustainability initiatives in ergonomics hinges on an examination of ergonomics’ own epistemology and ethics. The epistemology of ergonomics is fundamentally empiricist and positivist. This places practical constraints on its ability to address important issues such as sustainability, emergence and complexity. The implicit ethical position of ergonomics is one of neutrality, and its positivist epistemology generally puts value-laden questions outside the parameters of what it sees as scientific practice. We argue, by contrast, that a discipline that deals with both technology and human beings cannot avoid engaging with questions of complexity and emergence and seeking innovative ways of addressing these issues.

Practitioner Summary: Ergonomics has largely modelled its research on a reductive science, studying parts and problems to fix. In sustainability efforts, this can lead to mere local adaptations with a negative effect on global sustainability. Ergonomics must consider quality of life globally, appreciating complexity and emergent effects of local relationships.     

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants

BACKGROUND: Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. METHODS: Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. RESULTS: Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. CONCLUSION: Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.     

The passage of homopolymeric RNA through small solid-state nanopores

Solid-state nanopores are widely acknowledged as tools with which to study local structure in biological molecules. Individual molecules are forced through a nanopore, causing a characteristic change in an ionic current that depends on the molecules' local diameter and charge distribution. Here, the translocation measurements of long (~5-30 kilobases) single-stranded poly(U) and poly(A) molecules through nanopores ranging from 1.5 to 8 nm in diameter are presented. Individual molecules are found to be able to cause multiple levels of conductance blockade upon traversing the pore. By analyzing these conductance blockades and their relative incidence as a function of nanopore diameter, it is concluded that the smallest conductance blockades likely correspond to molecules that translocate through the pore in predominantly head-to-tail fashion. The larger conductance blockades are likely caused by molecules that arrive at the nanopore entrance with many strands simultaneously. These measurements constitute the first demonstration that single-stranded RNA can be captured in solid-state nanopores that are smaller than the diameter of double-stranded RNA. These results further the understanding of the conductance blockades caused by nucleic acids in solid-state nanopores, relevant for future applications, such as the direct determination of RNA secondary structure.     

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.     

Molecular cloning of CYP1A from the estuarine fish Fundulus heteroclitus and phylogenetic analysis of CYP1 genes: update with new sequences

Since we published a phylogenetic analysis of the CYP1A subfamily in 1995, several additional full-length sequences have been reported, including three members of an entirely new subfamily, CYP1B. Two avian sequences were recently published, so that CYP1A sequence data are now available from three of the five major vertebrate lineages. The two new branches that have been added to the CYP1 family tree significantly add to our understanding of P450 evolution. The inclusion of the CYP1Bs to the phylogenetic analysis allows us to root inferred trees. Addition of the avian CYP1As indicates that the CYP1A1/CYP1A2 duplication present in the mammalian lineage may have occurred after the divergence of birds and mammals. The number of fish species from which full-length coding regions of CYP1A genes have been sequenced has increased from four (trout, plaice, toadfish, and scup) to nine. These include CYP1A sequences from tomcod, butterflyfish, sea bream, sea bass, and the full-length sequence of CYP1A from the killifish Fundulus heteroclitus that is reported here. Phylogenetic analyses incorporating the new fish CYP1A sequences support our original conclusion that the fish CYP1As are monophyletic and indicate that the genes are evolving at very different rates in different species.