A template for broad consent in biobank research. Results and explanation of an evidence and consensus-based development process.

BACKGROUND: Biobanks increasingly presume long-term storage of biomaterials and data that shall be used for future research projects which are today unspecified. Appropriate consent documents for sample donors must therefore explain the breadth of consent and other elements of the biobank governance framework. Recent reviews demonstrated high variability in what issues these documents mention or not and how the issues are explained. This might undermine the protection of sample donors, complicate networked biobank research, create research waste and impact on public trust. METHODS: A systematic analysis of international research guidelines and existing broad consent templates was performed. Based on this information an interdisciplinary expert group from the AKMEK (Permanent Working Party of German RECs) developed a draft template and organized a comprehensive stakeholder consultation. After revision the final template was consented by all 53 German RECs. RESULTS: This paper briefly explores the spectrum of potentially relevant issues for broad consent forms. It then elaborates the template and how it was designed to be applicable in different types of biobanks. DISCUSSION: To further improve the validity and applicability of broad consent forms in biobank and other big data research, practice evaluations are needed. We hope that in this regard the presented template supports the development of new consent forms as well as the evaluation and revision of existing ones.

Evaluation of the correlation between time corpses spent in in-ground graves and findings at exhumation.

To determine how long pathological findings persist after burial and which factors play a role in decomposition of a corpse, we evaluated all bodies exhumed under the auspices of the Institute of Legal Medicine at the Hannover Medical School between 1978 and 1997. A total of 87 exhumations (54 men, 33 women) were performed in this period. The time bodies remained buried varied between 5 days and 16.8 years (mean 1.5 years, median 2.3 months). Fifty-six percent of the bodies were exhumed after at most 3 months, 10% remained buried for greater than 3 years. Pathomorphological changes of the soft tissues and the internal organs remained evident after several months, in some cases after several years of burial. Overall, it was possible to evaluate internal organs after 5 years of burial. Bodies became mostly decomposed after approximately 8 years at the earliest, although it was still possible to evaluate some soft tissue remnants after 16.8 years. In stepwise logistic regression, both the length of time the body was buried (p < 0.00005) and the time of year (p < 0.0019) clearly affected the rate of physical change. The variables of sex (p = 0.33), age (p = 0.61) and changes in the integrity of the body before burial (trauma, autopsy before burial; p = 0.15) did not influence the physical state of the body after exhumation. Our data show that much information may be gained from an exhumation even after significant time has passed since burial.

Acceleration of ethanol elimination with fructose in man.

The elimination of ethanol is known to be accelerated by fructose. Studies of continuous infusions of both ethanol and fructose as the basis for quantitative calculations are not available. In healthy volunteers fructose infusions were given for several hours during and immediately after the end of ethanol infusions. Both increase and elimination of ethanol in blood were effected to the same extent by fructose when compared to control experiments. Average increases in the elimination rates of ethanol were up to 80%; however, each subject displayed individual variations.

Types of trauma in cases of homicide.

A group of 251 victims of homicide in the years 1978-1988 were examined to determine the causes of their injuries. It was found that 51.4% of homicide victims exhibited evidence of injuries due to blunt trauma, 31.9% were victims of sharp trauma and 29.5% suffered from strangulation. Less common were shootings (18.7%) and other traumata (4.0%). Males were most commonly victims of injuries caused by blunt (51.9%) and sharp (33.6%) trauma, possibly due to more frequent physical confrontations among men. Females also demonstrated injuries due to blunt trauma (50.8%), but strangulation was nearly equal (47.5%). Women were commonly murdered by the aggressor's bare hands within the setting of conflicts in relationships. In 36.7% of all cases, injuries were caused by a combination of aggressive traumas. Combined injuries were common in cases of strangulation (77.3%), blunt trauma (64.3%) and sharp trauma (46.9%), whereas shooting injuries were seldom combined (12.8%) because they were usually fatal alone. Female victims demonstrated combined fatal injuries more frequently than males, probably because conflicts in relationships can cause extreme emotional outbursts and thus lead to the use of multiple aggressive traumatisations.

Reliability of SE33 typing by capillary electrophoresis.

A ladder of 24 ACTBP2 (SE33) alleles was separated 175 times by denaturing capillary electrophoresis on an ABI Prism 310 Genetic Analyzer using polymer POP-4. The mean standard deviation of fragment size determination was 0.083 bp. Fragments in the whole allelic range of ACTBP2 could be typed with high precision and reproducibility if adjacent fragments differed by at least two nucleotides. The capacity of resolving 1 bp differences was tested by repeatedly running a ACTBP2*14.2/14.3/31.2/31.3 allelic mixture. The 14.2/14.3 fragment pair could be separated in 98%, the 31.2/31.3 fragment pair only in 65% of all runs. Reliable separation of this difficult fragment mixture could exclusively achieved by using POP-6.

[Detection of saliva traces using test strips]. / Nachweis von Speichelspuren Mittels Teststreifen.

The test strip Rapignost-Amylase (Behring) for the rapid determination of alpha-amylase in the urine is also suitable for the determination of salivary amylase in stains stored up to 6 weeks at room temperature. The stains are extracted with physiological saline (extraction time 30 min), then the application zone of the strip is wetted with the extract. Positive amylase-reaction is recognised as a reddish-violet colouration of the reaction zone. Biological stains with low amylase concentrations (urine semen, vaginal secretion, mucus) react amylase negative. The method is uncomplicated and can be completed within 30 min. The test strips are easily available and stable during storage. Therefore the determination of saliva with test strips should be preferred to the clinical methods if the storage times of the stain are not longer than 4-6 weeks. It is a suitable procedure to determine salivary stains for use in forensic biology.

Intrathoracic and subconjunctival petechiae in sudden infant death syndrome (SIDS).

The frequency and density of intrathoracic and subconjunctival petechiae was studied in 250 cases of SIDS and 69 controls. The control group included 37 infants with natural and 32 infants with traumatic causes of death. Intrathoracic petechiae were found significantly more frequently in the SIDS group (91.2% SIDS; 42% controls; p < 0.001) and were present at a higher density (p < 0.001). Subepicardial and thymic petechiae were detected at high density in older SIDS infants. Subconjunctival petechiae were low in density and found only in 2.4% of the SIDS group but they were detected in 8.1% of the natural death group and 21.9% (p < 0.05) of the lethal trauma group. Subconjunctival petechiae were found at highest density in strangulation. Intrathoracic petechiae are commonly found in SIDS but are not specific for SIDS. Subconjunctival petechiae are typical but not specific for strangulation. In SIDS, subconjunctival petechiae are rare and appear at low density.

Lethal child neglect.

The jurisdiction of the Hannover Institute of Legal Medicine recently experienced an unusually high incidence of lethal child neglect, with three cases in a 5-month period in 1999. Case 1: A girl received an inappropriate and inadequate diet of tea and oatmeal. The child was never breastfed, nor did it ever receive any other formula. The parents report the infant to have been healthy until she suddenly began projectile vomiting at the age of 13 weeks. For the next 3 days the infant was not able to maintain an adequate intake. The mother reports finding the child dead in its bed on the morning of the fourth day. Attempts by medical personnel to revive the child were unsuccessful. Case 2: A mother began spoon-feeding the infant puree on the fourth day of life, which according to the manufacturer's specifications is suitable for children between 4 and 8 months of age. At the age of 5 weeks, the infant was reported to have vomited half the just previously ingested meal, after which she took a nap. Some time later the parents observed the infant to be quite pale, however, assumed this was a result of sleep. When the mother finally did pick her up, the child was lifeless, and the parents brought her to the hospital. Medical personnel could however, only declare the infant dead, documenting a rectal temperature of 30 degrees C. Case 3: A 3.5-year-old girl died after her mother left the locked apartment and did not return for several weeks. The body of the child was found lying dressed on the floor in a state of advanced decay and mummification. Common findings in all three cases include lack of prenatal care, home birth without the help of a midwife, low socioeconomic status or maternal alcohol abuse, body weights below the 3rd percentile, extreme dehydration, fatty hepatic degeneration, thymic atrophy and signs of aspiration.

Unexpected findings in the investigation of an airplane crash.

We report on the discovery at autopsy of an unexpected cause of a crash during landing of a small sports plane with four people on board. Surprisingly, an intact bullet and fragments of the casing were found in the body of the pilot. As expected, autopsy of the other passengers predominantly revealed signs of polytraumatization. In addition, one passenger had a tunnel wound to the left hand and another, a soft tissue tear between the thumb and forefinger of the right hand. These wounds were considered to be associated with a shooting incident in the cabin. The autopsy findings and additional gunpowder trace investigations suggested that the pilot had been incapacitated by a shot from behind, resulting in the plane crash. The present findings underscore the importance of conducting autopsies on all air crash victims.

The effect of lethal electrical shock on postmortem serum myoglobin concentrations.

Postmortem serum myoglobin concentrations in blood from the femoral vein (peripheral withdrawal) and the heart (central withdrawal) of nine electrical fatalities were compared with those of 74 individuals who had died of other causes. Independent of the cause of death or topographical site, serum myoglobin concentrations rose dramatically with the passage of postmortem time (maximum concentrations in the control group: 975,100 micrograms/l). In 59% of the total sample (electrical fatalities plus controls), serum myoglobin concentrations were higher in the central blood, in the other 41% the concentrations were higher in the peripheral blood. The differences in concentrations between the peripheral and the central withdrawal area correlated with neither the postmortem interval nor the cause of death. Up to the second day postmortem there was a statistically significant difference in serum myoglobin concentrations between electrical fatalities and controls. The individual values within each group, however, varied widely and overlapped between groups. Controls who had also suffered muscle injury (polytrauma, myocardial infarction) did not have significantly higher serum myoglobin concentrations than controls without muscle injury. Myoglobin concentrations appear to be greatly influenced by the extent and duration of the muscle cramps induced by the electrical current. Correct interpretation of serum myoglobin concentrations depends on the knowledge of events surrounding the lethal electrical shock. Postmortem determination of serum myoglobin concentrations alone is, therefore, not sufficient to establish intravital exposure to electrical current and can aid the diagnosis only in special cases.

The time-dependent expression of fibronectin, MRP8, MRP14 and defensin in surgically treated human skin wounds.

Fibronectin, MRP8, MRP14 and defensin were detected immunohistochemically in 46 surgically treated, fresh (hours old) human wounds and in wounds of 13 individuals who died immediately from fatal trauma (airplane crashes or train rollovers). In immediate fatal trauma, it was not possible to detect fibronectin outside of bleeding areas nor could inflammatory cells be visualized in the interstitium using MRP8, MRP14, or defensin antibodies. Fibronectin staining could be regularly demonstrated in wounds at least 20 min-old. Granulocytic infiltrates limited to the perivasal space could be detected 20-30 min after infliction of the wound expressing MRP8, MRP14 and defensin. It was also possible to detect fibronectin networks and MRP8-, MRP14-, and defensin-positive granulocytes and macrophages in particular wounds up to 30 days-old. No differences between the expression of MRP8 and MRP14 could be demonstrated in the wounds, the majority of which were only several hours old. As wound age increased, the number of defensin-positive granulocytes detected decreased. The immunohistochemical detection of fibronectin is a useful way to demonstrate vitality in fresh wounds, beginning about 20-30 min post-trauma. However, detection of MRP8, MRP14 and defensin provides no advantage over the routine histological detection of granulocytes and macrophages in wounds under 1-2 days old.

Accidental autoerotic deaths between 1978 and 1997. Institute of Legal Medicine, Medical School Hannover.

Between 1978 and 1997 the Institute of Legal Medicine of the Hannover Medical School examined 17 fatal autoerotic deaths. The incidence for the Hannover region was 0.49 cases per million inhabitants per year. The victims included 17 men with an average age of 36.8 years; a peak in the age distribution was seen between 20 and 29 years. Twelve of the men were found by friends or family in a domestic environment, while other situations in which the victims were found included the victim's own car, a hotel room, a canal embankment, a public parking lot as well as the holding cell of the youth detention center. The men were of varying socioeconomic status and held a number of different types of jobs or still attended school. Five of the men were found completely nude, while five were only undressed below the waist. Four men wore women's clothes and two were fully clothed with exposed genitals. Besides women's clothes, other objects found at the scene included various types of sexual aids, including ropes, chains, metal bars, locks, sex magazines, condoms, plastic bags, rubber items, etc. In four cases blood alcohol levels between 0.1 and 2.5 per thousand (urine alcohol levels between 0.2 and 2.5 per thousand ) were found. Toxicologic examination revealed chloroform, ketamine, a propane-butane gas mixture in one case each, and in two cases cocaine and morphine. Causes of death included central paralysis after strangulation (seven cases), asphyxiation (4), subarachnoid hemorrhage (2), intoxication (1), hypothermia (1), left heart failure (1), and drowning (1). The history, findings at scene, and autopsy findings and, in individual cases, other investigations are of utmost importance to accurately reconstruct a fatal autoerotic accident.

Fatal aviation accidents in Lower Saxony from 1979 to 1996.

So far no national or regional studies have been published in Germany regarding the number of fatal aviation accidents and results of autopsy findings. Therefore, we evaluated all fatal aviation accidents occurring in Lower Saxony from 1979 to 1996. A total of 96 aviation accidents occurred in this period involving 73 aeroplanes. The crashes resulted in the death of 154 people ranging in age from 19 to 68 years. The greatest number of victims in a single crash of an aircraft was (n=7). Other types of fatal accidents were crashes of aircraft and helicopter while on the ground (n=5), hot-air balloons (n=2), parachutes (n=10), hang glider accidents (n=5) and the striking of a bystander by a model airplane. Autopsies were performed on 68 of the 154 victims (44.2%), including 39 of the 73 pilots (53.4%). Some of the autopsies yielded findings relevant to the cause of the accident: gunshot wounds, the presence of alcohol or drugs in blood and preexisting diseases. Our findings emphasize the need for autopsy on all aviation accident victims, especially pilots, as this is the only reliable method to uncover all factors contributing to an accident.

[The relevance of urinary bladder filling in suprapubic bladder catheterization]. / Die Relevanz der Harnblasenfüllung bei der suprapubischen Blasenkatheterisierung.

Suprapubic punction of the urinary bladder (cystostomy) may cause typical, sometimes lethal injuries of pelvic organs especially in cases of an insufficient bladder filling. Some of these cases were described in the literature of legal medicine. To verify the importance of the cranial displacement of the vulnerable intestine by a filled bladder, the distances between the upper end of the symphysis and apex vesicae were measured in 76 forensic autopsies in situ and correlated with the filling volume of the urinary bladder. 69,2% of cases with a bladder filling volume up to 200 ml showed a suprapubic distance of only < or =4 cm. However, this distance collides with the preferred clinical intervention point, 2 fingers above the symphysis. In all cases with a bladder filling volume > or =300 ml, the distances were > or =5 cm. Based on our measurements, we recommend a preoperative bladder filling of > or =300 ml for an uncomplicated insertion of a suprapubic catheter.

[The "Alcomat" breath alcohol analyzer in a controlled drinking trial]. / Das Atemalkoholtestgerät "ALCOMAT" im kontrollierten Trinkversuch.

In controlled drinking tests according to a concrete forensic problem the residual-alcohol detector of the breath alcohol analyzer "ALCOMAT" was checked in relation to the actual blood alcohol concentration. The tests with non-alcoholic persons, rinsing the mouth with US-whiskey (40 ml, 30 seconds), showed first residual-alcohol indication and later blood alcohol levels up to 0.26%. The test groups with beforehand blood alcohol concentration showed either with mouth rinsing, or with real whiskey ingestion indicated devitations up to 2.07% according to 130% of the actual BAC. A correlation with the level of BAC was not found. The electronic precautionary fittings of the "ALCOMAT" are even under best possible controlled test conditions not sufficient reliable for forensic purpose.

[Arterial and venous alcohol elimination in 10 polytrauma patients]. / Arterielle und venöse Alkoholelimination bei 10 polytraumatisierten Patienten.

Alcohol elimination was examined in 10 patients involved in accidents while intoxicated. The influence of trauma, particularly polytrauma resulting in haemorrhage shock and its therapeutic treatment were analysed. The blood alcohol concentrations were determined according to the usual forensic criteria (2 alcohol dehydrogenase and 2 gas chromatography measurements). Observation periods ranged from 3 hours 45 minutes to 12 hours 35 minutes, with blood being drawn at intervals ranging from 45 minutes to 185 minutes (on average 70 minutes). Results of two patients (delta 60 = 0.22/1000/h and 0.28/1000/h) who only had 3 venous drawn and results of a deceased patient from whom only four arterial samples could be obtained (beta 60 = 0.21/1000/h) were disregarded when working out the average values. The blood alcohol curve plateaued in the case of the deceased patient as well as in the case of a patient whose hepatic circulation was curtailed for approximately half an hour during surgery. The blood alcohol curves for the remaining patients for uniformly linear with beta 60 values between 0.17/1000/h and 0.21/1000/h (mean = 0.18/1000/h +/- 0.01) in arterial samples and 0.18/1000/h and 0.21/1000/h (mean = 0.18/1000/h +/- 0.01) in venous samples. Given our results and the existing literature, we feel that retrograde calculations of the BAC can be justified in patients with polytrauma, despite the small number of patients included in the study. Naturally, the usual forensic criteria have to be taken into account, as well as individual situations. Examples that can be mentioned here are liver failure or curtailment of hepatic circulation during surgery.

[Forensic evaluation of manual temperature estimation]. / Die forensische Bewertung manueller Temperaturschätzungen.

The policemen sometimes feel the bonnet of a car for warmth to check wether it had been used just before. But in court it is difficult to quantify the temperature of the car. Therefore, 541 volunteers were given warmed steel plates to feel at different ambient temperatures between -8 degrees C and 30 degrees C and were asked to estimate their temperature. Highest and lowest temperatures for estimating metal plates as hot, warm, slightly warm or cold were measured. Combined with the known decrease of temperature after using an engine, the time at which the engine stopped can be estimated after this study. The sense of warmth and coldness turned out to be significantly influenced by the ambient temperature, by the time of day and by the volunteers' energy balance. In the morning volunteers estimated temperatures 2.5 degrees C higher and more precisely than in the afternoon and evening. For hungry volunteers the seemed 2.5 degrees C colder than for volunteers with a postprandially elevated energy balance. The lowest necessary temperature to cause a slightly warm sensation was 16 degrees C lower at -8 degrees C ambient temperature than at 30 degrees C ambient temperature. The risk of estimating a plate as warm by mistake was found in only 0.57%. Confirmed by this study, estimated temperatures can be considered reliable enough to cite in court.

[Experimental studies of the development of linear electric current marks]. / Experimentelle Untersuchungen zur Entstehung linearer Strommarken.

UNLABELLED: By means of reconstructing electric current pathways electrophysical conditions were explored causing electrocution death in the bathtub, according to many authors quite often indicated by linear electric lesions. In our experimental settings we observed appearance of circumscribed linear marks of pallor similar to electric lesions in the region of postmortem lividity of corpses at the same level as bathtub water. None of typical histological indicators could be seen in skin samples. So no evidence was given for electric burns even under conditions of high density and extended duration of current. Similar linear marks and equivalent histological results were found when corpses were put into the bathtub filled with cold water without any experimental electric contact. CONCLUSIONS: Linear marks of pallor may occur at water level even without any electric contact to corpse or water neither bathtub. IMPLICATIONS: According to specific conditions mentioned above linear so called electric lesions at water level do not indicate electric current yet lethal electric damage.

[Victims of homicide crimes--social conditions and circumstances of the crime]. / Opfer von Tötungsdelikten--soziale Situation und Tatumstände.

152 autopsies were performed in cases of homicide at the Institute for Legal Medicine of the Hannover Medical School and the documents concerning the social situation of the victims, the relationship between offenders and victims and the circumstances involved in the crime were analyzed. Among the victims who were employed, workers and craftsmen followed by the group working in the service industry and trade were most commonly involved. Foreigners were victimized in 8% of the cases. In 129 cases (88.4%) there was a single and in 11.6% multiple offenders. 78.3% of the victims were murdered by a person they knew. Among relatives (38.7%), parents were most frequently implicated (56.5%). Arguments were the most common reason followed by quarrels within relationships, robbery and sexual offences. In most cases, the location of the crime was the home of the victim or of the victim and offender. In 92.8% of the cases, the corpse was found at the location of the crime.

[Fatalities caused by exposure to heat]. / Todesfälle bei Hitzeeinwirkung.

Between 1978 and 1987 52 cases of death by burning or in connection with fire (13 females and 39 males) were examined at the Institute of Legal Medicine of the Medical School of Hannover. The causes were fires in flats (25), cars (15) and buildings(4), clothes set on fire (3) and explosions (3). In two cases death was caused by scalding. These cases could be divided into accidents (30), over 1/3 caused by smoking (11)), suicides (9) and homicides (6). The other seven cases could not be clarified definitively. Evidence of CO-elevation (38), soot inhalation (33), petechiae (11) and "crow's feet" (6) were noted. However, isolated findings cannot lead to a satisfactory assessment after death by burning. The reconstruction of events requires a comprehensive evaluation of the case history, the scene of death and the autopsy as well as complementary analyses. Therefore intensive cooperation between criminal investigators and forensic physicians is absolutely necessary.