The origin of evidence.

Forensic science is an applied science based on the laws of physics and chemistry. Over time, a set of fundamental concepts has developed that apply specifically to a forensic analysis. Traditionally, five concepts have been articulated: transfer, identification, individualization, association between source and target, and reconstruction. We suggest that an additional sixth concept, the idea that matter must divide before it can be transferred, is necessary to complete the paradigm. Divisible matter is particularly useful in describing physical match evidence. Additionally, we propose a paradigm that logically divides into scientific principles that govern the generation of evidence, and processes that pertain to the recognition, analysis, and interpretation of evidence. The principles of divisible matter and transfer pertain to the generation of evidence before and during the crime event; the processes of identification, classification or individualization, association, and reconstruction describe the practice of forensic science starting with the recognition of an item as evidence.

Chronic pain rehabilitation: principles and practice.

Chronic pain affects more than 50 million Americans and costs the economy billions of dollars each year. Because chronic pain may involve physical, emotional and social-role dysfunction, treatments that only address the physical problems are often ineffective. In chronic pain rehabilitation, a team of skilled professionals employs multiple therapies and a structured treatment plan to address all the dimensions of chronic pain. Patients undergoing pain rehabilitation demonstrate lasting reductions in pain, improved coping skills, and improved physical and social function. This article reviews the basic principles and current practice of chronic pain rehabilitation, with a guide to the evaluation techniques and therapies employed to aid these most challenging patients.

Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive?

This is a multisite study examining the internal validity and comprehensiveness of the International Association for the Study of Pain (IASP) diagnostic criteria for Complex Regional Pain Syndrome (CRPS). A standardized sign/symptom checklist was used in patient evaluations to obtain data on CRPS-related signs and symptoms in a series of 123 patients meeting IASP criteria for CRPS. Principal components factor analysis (PCA) was used to detect statistical groupings of signs/symptoms (factors). CRPS signs and symptoms grouped together statistically in a manner somewhat different than in current IASP/CRPS criteria. As in current criteria, a separate pain/sensation criterion was supported. However, unlike in current criteria, PCA indicated that vasomotor symptoms form a factor distinct from a sudomotor/edema factor. Changes in range of motion, motor dysfunction, and trophic changes, which are not included in the IASP criteria, formed a distinct fourth factor. Scores on the pain/sensation factor correlated positively with pain duration (P<0. 001), but there was a negative correlation between the sudomotor/edema factor scores and pain duration (P<0.05). The motor/trophic factor predicted positive responses to sympathetic block (P<0.05). These results suggest that the internal validity of the IASP/CRPS criteria could be improved by separating vasomotor signs/symptoms (e.g. temperature and skin color asymmetry) from those reflecting sudomotor dysfunction (e.g. sweating changes) and edema. Results also indicate motor and trophic changes may be an important and distinct component of CRPS which is not currently incorporated in the IASP criteria. An experimental revision of CRPS diagnostic criteria for research purposes is proposed. Implications for diagnostic sensitivity and specificity are discussed.

External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain.

Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.

RPD3 (REC3) mutations affect mitotic recombination in Saccharomyces cerevisiae.

Prior research identified the recessive rec3-1ts mutation in Saccharomyces cerevisiae which, in homozygous diploid cells, confers a conditional phenotype resulting in reduced levels of spontaneous mitotic recombination and loss of sporulation at the restrictive temperature of 36 degrees C. We found that a 3.4-kb genomic fragment that complements the rec3-1ts/rec3-1ts mutation and which maps to chromosome XIV, is identical to RPD3, a gene encoding a histone de-acetylase. Sporulation is reduced in homozygous diploid strains containing the rec3-1ts allele at 24 degrees C, suggesting that this allele of RPD3 encodes a gene product with a reduced function. Sporulation is abolished in diploid strains homozygous for the rpd3Delta or rec3-1ts alleles, as well as in rpd3Delta/rec3-1ts heteroallelic diploids, at the non-permissive temperature. Acid-phosphatase expression has been shown to be RPD3 dependent. We found that acid-phosphatase activity is greater in diploid strains homozygous for the temperature-sensitive rec3-1ts allele than in RPD3/RPD3 strains and increased further when mutant strains are grown at 36 degrees C. We also tested the rpd3Delta/rpd3Delta strains for their effects on spontaneous mitotic recombination. By assaying a variety of intra- and inter-genic recombination events distributed over three chromosomes, we found that in the majority of cases spontaneous mitotic recombination was reduced in diploid rpd3Delta/rpd3Delta cells (relative to a RPD3/RPD3 control). Finally, although 90% of mitotic recombinant events are initiated in the G1 phase of the growth cycle (i.e., before DNA synthesis) we show that RPD3 is not regulated in a cell-cycle-dependent manner. These data suggest that mitotic recombination, in addition to gene expression, is affected by changes in chromatin architecture mediated by RPD3.

Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated.

HO endonuclease-induced double-strand breaks in Saccharomyces cerevisiae can undergo recombination by two distinct and competing pathways. In a plasmid containing a direct repeat, in which one repeat is interrupted by an HO endonuclease cut site, gap repair yields gene conversions while single-strand annealing produces deletions. Consistent with predictions of the single-strand annealing mechanism, deletion formation is not accompanied by the formation of a reciprocal recombination product. Deletions are delayed 60 min when the distance separating the repeats is increased by 4.4 kb. Moreover, the rate of deletion formation corresponds to the time at which complementary regions become single stranded. Gap repair processes are independent of distance but are reduced in rad52 mutants and in G1-arrested cells.

Coordination of mastication and swallowing.

The coordination of mastication, oral transport, and swallowing was examined during intake of solids and liquids in four normal subjects. Videofluorography (VFG) and electromyography (EMG) were recorded simultaneously while subjects consumed barium-impregnated foods. Intramuscular electrodes were inserted in the masseter, suprahyoid, and infrahyoid muscles. Ninety-four swallows were analyzed frame-by-frame for timing of bolus transport, swallowing, and phases of the masticatory gape cycle. Barium entered the pharynx a mean of 1.1 s (range -0.3 to 6.4 s) before swallow onset. This interval varied significantly among foods and was shortest for liquids. A bolus of food reached the valleculae prior to swallow onset in 37% of sequences, but most of the food was in the oral cavity at the onset of swallowing. Nearly all swallows started during the intercuspal (minimum gape) phase of the masticatory cycle. Selected sequences were analyzed further by computer, using an analog-to-digital convertor (for EMG) and frame grabber (for VFG). When subjects chewed solid food, there were loosley linked cycles of jaw and hyoid motion. A preswallow bolus of chewed food was transported from the oral cavity to the oropharynx by protraction (movement forward and upward) of the tongue and hyoid bone. The tongue compressed the food against the palate and squeezed a portion into the pharynx one or more cycles prior to swallowing. This protraction was produced by contraction of the geniohyoid and anterior digastric muscles, and occurred during the intercuspal (minimum gape) and opening phases of the masticatory cycle. The mechanism of preswallow transport was highly similar to the oral phase of swallowing. Alternation of jaw adductor and abductor activity during mastication provided a framework for integration of chewing, transport, and swallowing.

Genetic and physical analysis of double-strand break repair and recombination in Saccharomyces cerevisiae.

We have investigated HO endonuclease-induced double-strand break (DSB) recombination and repair in a LACZ duplication plasmid in yeast. A 117-bp MATa fragment, embedded in one copy of LACZ, served as a site for initiation of a DSB when HO endonuclease was expressed. The DSB could be repaired using wild-type sequences located on a second, promoterless, copy of LACZ on the same plasmid. In contrast to normal mating-type switching, crossing-over associated with gene conversion occurred at least 50% of the time. The proportion of conversion events accompanied by exchange was greater when the two copies of LACZ were in direct orientation (80%), than when inverted (50%). In addition, the fraction of plasmids lost was significantly greater in the inverted orientation. The kinetics of appearance of intermediates and final products were also monitored. The repair of the DSB is slow, requiring at least an hour from the detection of the HO-cut fragments to completion of repair. Surprisingly, the appearance of the two reciprocal products of crossing over did not occur with the same kinetics. For example, when the two LACZ sequences were in the direct orientation, the HO-induced formation of a large circular deletion product was not accompanied by the appearance of a small circular reciprocal product. We suggest that these differences may reflect two kinetically separable processes, one involving only one cut end and the other resulting from the concerted participation of both ends of the DSB.

Efficient repair of HO-induced chromosomal breaks in Saccharomyces cerevisiae by recombination between flanking homologous sequences.

Novel recombinational repair of a site-specific double-strand break (DSB) in a yeast chromosome was investigated. When the recognition site for the HO endonuclease enzyme is embedded in nonyeast sequences and placed between two regions of homology, expression of HO endonuclease stimulates recombination between the homologous flanking regions to yield a deletion, the apparent product of an intrachromosomal exchange between direct repeats. This deletion-repair event is very efficient, thus preventing essentially all the potential lethality due to the persistence of a DSB. Interestingly, unlike previous studies involving spontaneous recombination between chromosomal repeats, the recombination events stimulated by HO-induced DSBs are accompanied by loss of the sequences separating the homologous regions greater than 99.5% of the time. Repair is dependent on the RAD52 gene. The deletion-repair event provides an in vivo assay for the sensitivity of any particular recognition site to HO cleavage. By taking advantage of a galactose-inducible HO gene, it has been possible to follow the kinetics of this event at the DNA level and to search for intermediates in this reaction. Deletion-repair requires approximately 45 min and is inhibited when cycloheximide is added after HO endonuclease cleavage.

New motor control assessment techniques for evaluating individuals with severe handicaps: a case study.

Prescription of assistive devices for motor-handicapped individuals requires assessment of their motor capabilities. When patients' motor deficits are particularly severe, wide individual differences in the location and type of abnormalities complicate the assessment process. The precision of assessment has been greatly increased in recent years by the use of quantitative, computer-aided motion analysis, which facilitates statistical examination and comparison with normal individuals. This paper discusses a case study wherein a 24-year-old male nonvocal cerebral palsy patient was assessed for his ability to operate assistive communication devices. Three computer-aided measurement protocols were employed to evaluate the patient and two controls: performance using the patient's existing communication aid was evaluated in terms of rate and accuracy of communication using standardized spelling and response time tasks; volitional myoelectric activity was surveyed to identify possible myoelectric control sites for communication aid operation; a study of head position and its time derivatives was conducted to explore the feasibility of proportional control of a communication aid. Comparison of handicapped and control subject data indicated that, despite several characteristic motor control deficits, the handicapped subject was capable of proportional control of lateral head rotation and binary control of frontalis myoelectric signals. These movements could be used to operate a proportionally-controlled, direct-selection communication aid that could substantially increase the subject's communication rate. Work in progress includes the expansion of the handicapped and unimpaired subject databases and further development of the techniques discussed here to include three-dimensional motion analysis and objective measurement of muscle fatigue.