Laboratory-based Strategies Research Articles

Screening fasting glucose before the OGTT: near-patient glucometer- or laboratory-based measurement?

The measurement of fasting glucose is a common practice for lowering the risk of hyperglycemia before an oral glucose tolerance test (OGTT). In this study we analyze advantages and limitations of near-patient measurement of capillary fasting glucose with a portable glucometer or blood sampling and measurement of plasma glucose with laboratory instrumentation. The final study population consisted of 241 subjects (mean age: 36±8 years; 97.9 % pregnant women) referred to our local phlebotomy center for an OGTT. Fasting glucose was measured in capillary blood using a near-patient glucometer (glucometer-based strategy) and in plasma with laboratory instrumentation using the hexokinase reference assay (laboratory-based strategy). The mean turnaround time from sample collection to obtaining the glucose value was longer with the laboratory-based strategy (32 min 8 vs. 8 s). The imprecision of the glucometer was higher than that of the laboratory assay (3.4 vs. 0.8 %). A negative bias of-3.3 % in fasting glucose was found with the glucometer compared to the laboratory measurement. The diagnostic accuracy, sensitivity and specificity of the glucometer for detecting fasting glucose values≥7.0 mmol/L were 99.2 , 50.0 and 100.0 % compared to the laboratory assay. The glucometer-based strategy had an incremental cost of 0.17€ per patient compared to the laboratory-based strategy. Screening fasting glucose in capillary blood with a near-patient glucometer instead of measuring fasting plasma glucose with laboratory instrumentation allows faster patient management in the phlebotomy center but is associated with higher imprecision, inaccuracy, costs and avoidable finger pricks.

A Novel Laboratory-Based Strategy for Single Adipocyte and Adipose-Derived Stem Cells Extraction for Transplantation: An Experimental Research.

Autologous fat grafting is widely used in plastic surgery. However, its main limitation is the low survival rate of fat grafts after transplantation. Transplantation of single adipocytes in combination with adipose-derived stem cells (ADSCs) could largely preserve the activity of the fat and improve graft survival. To verify the long-term survival rate of single adipocyte graft in vivo and its viable fat morphology for future fat grafting. Healthy adipose tissue was harvested and disassociated using fat dissociation solution, the Single-cell Suspension Preparation System (SSPS) was used to obtain a mixture of single adipocytes, ADSCs and stromal vascular fraction (SVF), and the structure of single adipocytes was verified by cell mask red and DAPI double staining. Nine male Balb/c nude mice were used, and three different graft volumes were established (0.05, 0.1 and 0.2ml). For each mouse, four sites were selected for transplantation, one for macrofat and the other three for single adipocytes, and different transplant volumes 30, 60 and 90days after transplantation. In each period, 3mice were selected to measure the volume of fat graft. Double staining with cell mask red and DAPI confirmed that the nucleus was identified intracellularly, which also indicated that the adipocytes in the single-cell suspension were structurally complete. When evaluating the transplantation, the groups with a volume of 0.05 ml and 0.2ml performed better in the single-cell fat group in all transplantation periods, the group with a volume of 0.1ml performed better in the single-cell group in the 30- and 60-day transplantation, and the differences were significant (P<0.05). In this study, the SSPS was used to obtain a new transplant material containing single adipocytes and ADSCs by enzymatic hydrolysis of adipose tissue and converted into single cells. It effectively improved the survival rate of fat grafting and the long-term effect of transplantation. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Near-infrared hyperspectral imaging for online measurement of the viability detection of naturally aged watermelon seeds.

The viability status of seeds before sowing is important to farmers as it allows them to make yield predictions. Monitoring the seed quality in a rapid and nondestructive manner may create a perfect solution, especially for industrial sorting applications. However, current offline laboratory-based strategies employed for the monitoring of seed viability are time-consuming and thus cannot satisfy industrial needs where there is a substantial number of seeds to be analyzed. In this study, we describe a prototype online near-infrared (NIR) hyperspectral imaging system that can be used for the rapid detection of seed viability. A wavelength range of 900-1700 nm was employed to obtain spectral images of three different varieties of naturally aged watermelon seed samples. The partial least square discriminant analysis (PLS-DA) model was employed for real-time viability prediction for seed samples moving through a conveyor unit at a speed of 49 mm/sec. A suction unit was further incorporated to develop the online system and it was programmatically controlled to separate the detected viable seeds from nonviable ones. For an external validation sample set showed classification accuracy levels of 91.8%, 80.7%, and 77.8% in relation to viability for the three varieties of watermelon seed with healthy seedling growth. The regression coefficients of the classification model distinguished some chemical differences in viable and nonviable seed which was verified by the chromatographic analysis after the detection of the proposed online system. The results demonstrated that the developed online system with the viability prediction model has the potential to be used in the seed industry for the quality monitoring of seeds.

Protein deep profile and model predictions for identifying the causal genes of male infertility based on deep learning

A principal task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. Millions of genes have been sequenced in data-driven genomics era, but their causal relationships with disease phenotypes remain limited, due to the difficulty of elucidating underlying causal genes by laboratory-based strategies. Here, we proposed an innovative deep learning computational modeling alternative (DPPCG framework) for identifying causal (coding) genes for a specific disease phenotype. In terms of male infertility, we introduced proteins as intermediate cell variables, leveraging integrated deep knowledge representations (Word2vec, ProtVec, Node2vec, and Space2vec) quantitatively represented as ‘protein deep profiles’. We adopted deep convolutional neural network (CNN) classifier to model protein deep profiles relationships with male infertility, creatively training deep CNN models of single-label binary classification and multi-label eight classification. We demonstrate the capabilities of DPPCG framework by integrating and fully harnessing the utility of heterogeneous biomedical big data, including literature, protein sequences, protein–protein interactions, gene expressions, and gene–phenotype relationships, and effective indirect prediction of 794 causal genes of male infertility and associated pathological processes. We present this research in an interactive ‘Smart Protein’ intelligent (demo) system (http://www.smartprotein.cloud/public/home). Researchers can benefit from our intelligent system by (i) accessing a shallow gene/protein-radar service involving research status and a knowledge graph-based vertical search; (ii) querying and downloading protein deep profile matrices; (iii) accessing intelligent recommendations for causal genes of male infertility and associated pathological processes, and references for model architectures, parameter settings, and training outputs; and (iv) carrying out personalized analysis such as online K-Means clustering.

Laboratory-Based Resources for COVID-19 Diagnostics: Traditional Tools and Novel Technologies. A Perspective of Personalized Medicine.

The coronavirus infection 2019 (COVID-19) pandemic, caused by the highly contagious SARS-CoV-2 virus, has provoked a global healthcare and economic crisis. The control over the spread of the disease requires an efficient and scalable laboratory-based strategy for testing the population based on multiple platforms to provide rapid and accurate diagnosis. With the onset of the pandemic, the reverse transcription polymerase chain reaction (RT-PCR) method has become a standard diagnostic tool, which has received wide clinical use. In large-scale and repeated examinations, these tests can identify infected patients with COVID-19, with their accuracy, however, dependent on many factors, while the entire process takes up to 6–8 h. Here we also describe a number of serological systems for detecting antibodies against SARS-CoV-2. These are used to assess the level of population immunity in various categories of people, as well as for retrospective diagnosis of asymptomatic and mild COVID-19 in patients. However, the widespread use of traditional diagnostic tools in the context of the rapid spread of COVID-19 is hampered by a number of limitations. Therefore, the sharp increase in the number of patients with COVID-19 necessitates creation of new rapid, inexpensive, sensitive, and specific tests. In this regard, we focus on new laboratory technologies such as loop mediated isothermal amplification (LAMP) and lateral flow immunoassay (LFIA), which have proven to work well in the COVID-19 diagnostics and can become a worthy alternative to traditional laboratory-based diagnostics resources. To cope with the COVID-19 pandemic, the healthcare system requires a combination of various types of laboratory diagnostic testing techniques, whodse sensitivity and specificity increases with the progress in the SARS-CoV-2 research. The testing strategy should be designed in such a way to provide, depending on the timing of examination and the severity of the infection in patients, large-scale and repeated examinations based on the principle: screening–monitoring–control. The search and development of new methods for rapid diagnostics of COVID-19 in laboratory, based on new analytical platforms, is still a highly important and urgent healthcare issue. In the final part of the review, special emphasis is made on the relevance of the concept of personalized medicine to combat the COVID-19 pandemic in the light of the recent studies carried out to identify the causes of variation in individual susceptibility to SARS-CoV-2 and increase the efficiency and cost-effectiveness of treatment.

Recent therapeutic advances in chronic lymphocytic leukemia.

The last several years have witnessed a paradigm shift in the management of patients with chronic lymphocytic leukemia (CLL). The course of this very heterogeneous disease, traditionally treated with chemotherapeutic agents usually in combination with rituximab, typically has been characterized by remissions and relapses, and survival times vary greatly, depending on intrinsic biological attributes of the leukemia. The developments of the last few years have been transformative, ushering in an era of novel, molecularly targeted therapies, made possible by extensive efforts to elucidate the biology of the disease that predated the new targeted drugs. Thus, successful therapeutic targeting of the B-cell receptor signaling pathway and of the Bcl-2 anti-apoptotic protein with small molecules has now made chemotherapy-free approaches possible, hopefully mitigating the risk of development of therapy-related myeloid neoplasms and making eventual cure of CLL with the use of optimal drug combinations a realistic goal. Most importantly, these therapies have demonstrated unprecedented efficacy in patients with deletion 17p/TP53 mutation, a subset that historically has been very difficult to treat. However, as we gain more experience with the newer agents, unique safety concerns and resistance mechanisms have emerged, as has the issue of cost, as these expensive drugs are currently administered indefinitely. Accordingly, novel laboratory-based strategies and clinical trial designs are being explored to address these issues. The availability of whole exome/genome sequencing has given us profound insights into the mutational landscape of CLL. In this article, we highlight some of the most impactful advances since this topic was last reviewed in this journal.

Cell-Free Circulating Epigenomic Signatures: Non-Invasive Biomarker for Cardiovascular and Other Age-Related Chronic Diseases.

The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.

Laboratory-based strategy using a new marketed polymerase chain reaction assay to manage diarrheic episodes among patients from rehabilitation and long-term care facilities

Management of Norovirus and Clostridium difficile gastroenteritis is challenging for rehabilitation and long-term care facilities. We evaluated the contribution of a 2-step laboratory-based strategy, including a new ready-to-use Norovirus polymerase chain reaction assay to promote isolation precautions. C difficile and Norovirus were successively identified from 17% and 23% of 52 episodes of diarrhea, respectively, during the winter season, leading to 100% adequate isolation measures. In patient populations with numerous risk factors for diarrhea, a combined laboratory-based approach could improve infection control.

Automatic laboratory-based strategy to improve the diagnosis of type 2 diabetes in primary care.

IntroductionTo study the pre-design and success of a strategy based on the addition of hemoglobin A1c (HbA1c) in the blood samples of certain primary care patients to detect new cases of type 2 diabetes.Materials and methodsIn a first step, we retrospectively calculated the number of HbA1c that would have been measured in one year if HbA1c would have been processed, according to the guidelines of the American Diabetes Association (ADA). Based on those results we decided to prospectively measure HbA1c in every primary care patient above 45 years, with no HbA1c in the previous 3 years, and glucose concentration between 5.6-6.9 mmol/L, during an 18 months period. We calculated the number of HbA1c that were automatically added by the LIS based on our strategy, we evaluated the medical record of such subjects to confirm whether type 2 diabetes was finally confirmed, and we calculated the cost of our intervention.ResultsIn a first stage, according to the guidelines, Hb1Ac should have been added to the blood samples of 13,085 patients, resulting in a cost of 14,973€. In the prospective study, the laboratory added Hb1Ac to 2092 patients, leading to an expense of 2393€. 314 patients had an HbA1c value ≥ 6.5% (48 mmol/mol). 82 were finally diagnosed as type 2 diabetes; 28 thanks to our strategy, with an individual cost of 85.4€; and 54 due to the request of HbA1c by the general practitioners (GPs), with a cost of 47.5€.ConclusionThe automatic laboratory-based strategy detected patients with type 2 diabetes in primary care, at a cost of 85.4€ per new case.

Strategies for the identification and tracking of cronobacter species: an opportunistic pathogen of concern to neonatal health.

Cronobacter species are emerging opportunistic food-borne pathogens, which consists of seven species, including C. sakazakii, C. malonaticus, C. muytjensii, C. turicensis, C. dublinensis, C. universalis, and C. condimenti. The organism can cause severe clinical infections, including necrotizing enterocolitis, septicemia, and meningitis, predominately among neonates <4 weeks of age. Cronobacter species can be isolated from various foods and their surrounding environments; however, powdered infant formula (PIF) is the most frequently implicated food source linked with Cronobacter infection. This review aims to provide a summary of laboratory-based strategies that can be used to identify and trace Cronobacter species. The identification of Cronobacter species using conventional culture method and immuno-based detection protocols were first presented. The molecular detection and identification at genus-, and species-level along with molecular-based serogroup approaches are also described, followed by the molecular sub-typing methods, in particular pulsed-field gel electrophoresis and multi-locus sequence typing. Next generation sequence approaches, including whole genome sequencing, DNA microarray, and high-throughput whole-transcriptome sequencing, are also highlighted. Appropriate application of these strategies would contribute to reduce the risk of Cronobacter contamination in PIF and production environments, thereby improving food safety and protecting public health.

Roots in the Great Plains: The Applied Psychology of Harry Hollingworth ed. by Ludy T. Benjamin Jr. and Lizette Royer Barton (review)

Reviewed by: Roots in the Great Plains: The Applied Psychology of Harry Hollingworth ed. by Ludy T. Benjamin Jr. and Lizette Royer Barton C. James Goodwin Roots in the Great Plains: The Applied Psychology of Harry Hollingworth. Edited by Ludy T. Benjamin Jr. and Lizette Royer Barton. Akron: University of Akron Press, 2013. vii + 349 pp. Illustrations, index. $34.95 paper. This book is the first of a two-volume autobiography highlighting the life and work of Nebraska native Harry Hollingworth (1880–1956), a figure well known among historians of psychology; he was a pioneer in the field that eventually came to be called industrial psychology. Although trained as a laboratory psychologist, Hollingworth made his reputation by completing applied research projects for a variety of corporations. The title of the second volume of the autobiography, From Coca-Cola to Chewing Gum: The Applied Psychology of Harry Hollingworth, hints at the range of Hollingworth’s applied projects. Both volumes are reprinted in facsimile format, part of a series of publications from the Center for the History of Psychology at the University of Akron; the purpose of the series is to make important archival material at the center widely available. Hollingworth wrote the autobiography in 1940, just a few years after the untimely death of his wife, research collaborator, and fellow Nebraskan, Leta Stetter Hollingworth (1886–1939). This first volume of the Hollingworth autobiography, especially the first two-thirds of it, will be of special value to those interested in the social and cultural history of the Great Plains at the end of the nineteenth century. It documents Hollingworth’s early years—his childhood and adolescence as a largely self-educated son of a carpenter in rural Nebraska, and the jobs he took on to save for and remain in college (ranging from teacher to carpenter to gravedigger). The final third of the volume, mainly his years at University of Nebraska, will interest historians of psychology, for it was here that Hollingworth’s future became determined when he encountered (1) the love of his life, Leta Stetter, and (2) what came to be called the New Psychology—a laboratory-based strategy for examining psychological phenomena. This was a time when psychology was separating itself from philosophy and physiology and becoming a discipline of its own—a transition reflected in Hollingworth’s stated ambition when entering Nebraska “to specialize in philosophy and in that new and decidedly vague thing called psychology” (250). At Nebraska, Hollingworth came under the influence of Thaddeus Bolton, a PhD student of G. Stanley Hall’s at Clark University, one of the first schools in the United States to offer graduate training in the New Psychology. Recognizing Hollingworth’s talent in his laboratory course, Bolton quickly hired him as a course assistant. This helped alleviate some of Hollingworth’s financial burden, while at the same time strengthening his commitment to this new field. Bolton became a lifelong colleague. This first volume of the autobiography ends with Hollingworth’s initial failure to get into graduate school, his brief time as a high school principal, and his eventual invitation to graduate study at Columbia University. Volume 2 of the autobiography documents the Columbia years and Hollingworth’s subsequent career as an applied psychologist. The strength of this first volume of the Hollingworth autobiography lies in the rich descriptions of the struggles of a young man trying to escape poverty in rural Nebraska and shape a meaningful life for himself. Although the level of detail is occasionally excessive, the patient reader will gain valuable insight into that independent, pull-yourself-up-by-your-bootstraps mentality (“the cult of self-reliance,” 69) characteristic of life in the often harsh environment of the Great Plains in the late nineteenth century. C. James Goodwin Department of Psychology Western Carolina University Copyright © 2015 Center for Great Plains Studies, University of Nebraska–Lincoln

Thinking Dynamically About Biological Mechanisms: Networks of Coupled Oscillators

Explaining the complex dynamics exhibited in many biological mechanisms requires extending the recent philosophical treatment of mechanisms that emphasizes sequences of operations. To understand how nonsequentially organized mechanisms will behave, scientists often advance what we call dynamic mechanistic explanations. These begin with a decomposition of the mechanism into component parts and operations, using a variety of laboratory-based strategies. Crucially, the mechanism is then recomposed by means of computational models in which variables or terms in differential equations correspond to properties of its parts and operations. We provide two illustrations drawn from research on circadian rhythms. Once biologists identified some of the components of the molecular mechanism thought to be responsible for circadian rhythms, computational models were used to determine whether the proposed mechanisms could generate sustained oscillations. Modeling has become even more important as researchers have recognized that the oscillations generated in individual neurons are synchronized within networks; we describe models being employed to assess how different possible network architectures could produce the observed synchronized activity.

Cost-effectiveness of laboratory monitoring for management of HIV treatment in sub-Saharan Africa

To compare the cost-effectiveness of three different strategies for long-term monitoring of antiretroviral therapy (ART) failure and regimen switching in sub-Saharan Africa: a symptom-based approach, or monitoring of either CD4 cell counts or plasma viral load (pVL). Markov model. Hypothetical HIV-infected adult population who began first-line ART and subsequently had up to 6 years of follow-up. Total cost, life expectancy and incremental cost-effectiveness ratio (ICER). A symptom-based approach yielded a life expectancy of 64.0 months at a total cost of US$ 4028 per person. All laboratory-based strategies, at testing intervals of 6 or 12 months, were cost-saving and improved life expectancy, compared with a symptom-based approach. The life-expectancy gain was larger for pVL than for CD4 strategies at 6-monthly (2.3 and 0.9 months, respectively) and 12-monthly testing (2.0 and 0.8 months, respectively). Cost-savings of 6-monthly pVL or CD4 testing were similar (US$ 630 and 621, respectively), whereas 12-monthly CD4 cell counts were more cost-saving than 12-monthly pVL (US$ 1132 and 880, respectively). Testing every 12 months - rather than every 6 months - decreased the ICER by 102% for CD4 cell count and 67% for pVL. These findings were robust to a wide range of deterministic sensitivity analyses, but were sensitive to the specificity and costs of diagnostic tests. Additional diagnostic costs are balanced by cost-savings from avoiding unnecessary switching due to misdiagnosis of ART failure. Routine pVL monitoring may be preferred as a replacement for CD4 cell counts because of its additional public-health advantages in preventing drug-resistance, supporting adherence and reducing HIV transmission.

Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury1

Oocytes from aging ovaries contain mitochondria with morphological and genetic flaws. How these flaws relate to phenotypes of oocyte developmental compromise associated with clinical infertility is not well understood. This study was conducted to investigate the role of mitochondria in the developmental compromises observed with female aging using a mouse model of mitochondrial dysfunction. Oocytes obtained from aging (30-40 wk) (C57BL/6J x CBACaH)F1 (B6CBAF1) hybrid female mice were photosensitized with mitochondrial fluorophore rhodamine-123 for variable durations and compared to similarly treated oocytes derived from pubertal mice (4-6 wk). Blastocyst development of normally fertilized oocytes from both age-groups correlated negatively in mathematically unique profiles with irradiation time, with a more sudden decline in development for oocytes from aging mice. Complete inhibition of blastocyst development occurred following a shorter duration of photosensitization for oocytes from aging compared to pubertal animals (60 vs. 90 sec). Prolonged photosensitization resulted in mitochondrial uncoupling and promoted localized generation of reactive oxygen species, mitochondrial permeabilization, and apoptotic phenotypes. Thus, aging oocytes are more developmentally sensitive to mitochondrial damage than pubertal oocytes but undergo similar metabolic and apoptotic responses. These and future findings may encourage further optimization of laboratory-based strategies to minimize mitochondrial injury to oocytes, particularly those from older women, and improve clinical outcomes for women with age-related etiologies of infertility.

Evaluation of alternating pressure air mattresses: one laboratory-based strategy

Although many different type of alternating pressure air mattresses (APAMs) are used for the prevention and treatment of pressure ulcers, few high quality randomised controlled trials are available on which to base purchasing decisions. Faced with this situation, physiological measurements are increasingly being used as a surrogate. Laboratory evaluation techniques have centred largely on interface pressure (IP) measurement, typically analysing discrete maximum and minimum levels, or average pressure. However, since pressure relief is time varying, a time-based analysis technique may be more suitable for performance assessment. Measurements of IP, mattress air cell pressure (AP), skin tissue perfusion using laser Doppler fluxmetry (LDF), transcutaneous oxygen (tcPO2) and carbon dioxide (tcPCO2) were taken simultaneously on the sacrum, heels, trochanters and buttock over at least two alternating cycles. Duration of IP below three thresholds (30, 20, and 10 mmHg) as well as the area under the tcPO2, tcPCO2 and LDF curves were calculated automatically. Ten healthy volunteers were recruited to evaluate the pressure-relieving characteristics of two different designs of APAMs. Results indicated significant differences between the products. During the deflation phase of the cycle contact pressures on the heel were significantly lower (p < 0.0001) on the device whose inflation pressure was significantly higher, although there was no significant difference in deflation pressure. Therefore, it is important to note that low APs do not necessarily produce lower IPs under the heel, contrary to the intuitive classical notion. These techniques could assist in the selection of alternating or dynamic surfaces of any description confirmed by further clinical validation.

Reasserting the Utility of Obsidian Hydration Dating: A Temperature-Dependent Empirical Approach to Practical Temporal Resolution with Archaeological Obsidians

In a recent paper in this journal, Anovitz et al. (1999) identify potentially serious flaws in the measurement and modelling of obsidian hydration for dating archaeological obsidians. This critique follows other recent papers highlighting potential problems with the method (e.g., Ridings, 1996; Stevenson, Mazer & Scheetz, 1998). Contrary to this latest critique, the current paper offers evidence for the apparent efficacy of a quadratic model for obsidian hydration dating of archaeological obsidians, using empirical results from archaeological projects throughout the western United States. It is posited that this model is sufficient, in part, due to limits of commonly used methods of hydration analysis, which also provide a cost-effective means for large-scale sampling. Given apparent support for quadratic modelling and, hence, the diffusion theory underlying it, an empirical approach to obsidian hydration rate formulation that incorporates field temperature data is explored. Although evaluation of the resulting rate formula for Casa Diablo obsidian is somewhat equivocal, the results are relatively robust when compared to other posited rates. As such, the approach appears to hold promise within the limits of temporal resolution necessary for many regional research strategies, while also serving as a potential check of laboratory-based strategies.

Foreword

Human genetics has traveled a remarkable course in this century. Starting with Garrod's recognition that inborn errors could be understood on the basis of Mendel's laws, progress in the field was long punctuated by remarkable flashes of insight but inhibited by the paucity of robust laboratory-based strategies for experimentation. That obstacle collapsed dramatically with the development of methods of recombinant DNA in the 1970s. Now human molecular biology became almost as accessible as that of other organisms, and Pope's admonition that “the proper study of man is man” became infinitely more attainable. Grounded in this powerful new array of experimental approaches, it is fair to say that human genetics is now emerging as the central science of medicine, focused as it is on the study of health and disease at the most basic level of the DNA blueprint. In the mid-1980s the possibility of initiating a coordinated effort to map and sequence the entire human genome was raised. After considerable and sometimes heated discussion in the scientific community, the Human Genome Project was born. Now, only 3 years into a planned 15-year effort, the Genome Project has already made major strides in producing a highly valuable genetic map of man, organizing the physical mapping of whole chromosomes, stimulating major advances in characterizing the genomes of several model organisms, and catalyzing the discovery of a large number of human disease genes by positional cloning. With its emphasis on large-scale efforts and the consequent need for efficiency and high throughput, the Genome Project has also had a noticeable effect on bench research in human genetics—with automation, robotics, and sophisticated computer science now invading the research laboratory where once hand-held pipets with handwritten lab books reigned supreme. Thus, the experimental basis of human genetics is in an era of rapid and powerful expansion, and the demand for well-tested and clearly described research protocols is at an all-time high. Many laboratories expend considerable effort developing their own in-house set of such methods; however, the vagaries of trying to test and document such protocols effectively in a small lab often produces suboptimal results, leading many bench researchers to agree with Winston Churchill that “success is nothing more than going from failure to failure with undiminished enthusiasm.” Far better, then, to organize an international effort to assemble the best of such protocols, as exemplified by this volume and its sister publications, Current Protocols in Molecular Biology and Current Protocols in Immunology. The continuously updated nature of the protocol collection (now available on CD-ROM, which will appeal to many high-tech genome laboratories), its thorough coverage of the field, and its responsiveness to user input should make this an invaluable asset to human genetics researchers well into the next century.

Cognitive therapy: A 30-year retrospective.

Several lines of investigation have evolved from the initial cognitive model of depression and other disorders. A large number of studies have tested the cognitive model using both clinical and laboratory-based strategies. In general, studies that most closely approximate the clinical conditions from which the theory was derived are supportive of the cognitive model of depression. Studies of anxiety and panic, although fewer, generally support the cognitive model of anxiety and panic. The application to the treatment of clinical problems has been promising and supports the concept of cognitive specificity. The cognitive therapy of depression has led to the utilization of specific cognitive strategies based on the specific conceptualizations of a given disorder to a wide variety of disorders. Study of abnormal reactions has also provided clues to the cognitive structure of normal reactions.