Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Following historical "tracks" of hair follicle miniaturisation in patterned hair loss: Are elastin bodies the forgotten aetiology?

Pattern hair loss (PHL) is a chronic regressive condition of the scalp, where follicular miniaturisation and decreased scalp hair coverage occurs in affected areas. In all PHL cases, there is a measurable progressive shortening of the terminal hair growth duration, along with reduced linear growth rates. In both genders, PHL initially shows an increase in short telogen hairs ≤30 mm in length, reflecting a cycle completion of under 6 months in affected terminal hair follicles. To understand the miniaturisation process, we re-examine the dynamics of miniaturisation and ask the question, "why do miniaturised hair follicles resist treatment?" In the light of recent developments in relation to hair regeneration, we looked back in the older literature for helpful clues "lost to time" and reprise a 1978 Hermann Pinkus observation of an array of elastin deposits beneath the dermal papilla following subsequent anagen/telogen transitions in male balding, originally described by Arao and Perkins who concluded that these changes provide a "morphologic marker of the entire biologic process in the balding scalp." Thus, we have reviewed the role of the elastin-like bodies in hair pathology and we propose that alterations in elastin architecture may contribute to the failure of vellus-like hair reverting back to their terminal status and may indicate a new area for therapeutic intervention.

Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls.

BACKGROUND: Hair loss is related to follicular density, programmed regrowth and hair productivity. OBJECTIVE: The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). METHODS: LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. RESULTS: We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females. LIMITATIONS: Caucasian ethnicity. CONCLUSION: In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males.

What is the evidence for gender differences in ferritin and haemoglobin?

Reference ranges for haemoglobin and ferritin in women of reproductive age are widely reported showing values that are lower than equivalent aged males. Similar values would be expected in the absence of different biological requirements. While reference ranges have been derived from data on large populations, it is likely that these populations have included significant numbers of women who are iron deficient in view of menstrual blood loss and poor dietary intake. Populations with a daily iron intake in excess of 100mg have shown that iron deficiency in females is rare. Studies reporting bone marrow with iron stains from 50 years ago pointed out that significant numbers of women were iron deficient and more recently serum ferritin studies have confirmed this. However, a large number of women in the Western world spend a significant part of their lives in a negative iron balance due to a combination of poor diet and menstrual blood loss. The presence of haem iron in the diet of humans enhances non-haem iron absorption but dietary surveys consistently report that women's diet is deficient in iron. Furthermore, the typical Western diet contains many common foods that limit iron absorption. It appears that lower haemoglobin and ferritin values in menstruating women have been accepted as normal rather than possibly representing widespread iron deficiency. Reference ranges should be re-evaluated in populations proven to be iron replete.

Diaphragmatic pathology: a cause of clinically unexplained death in the perinatal/paediatric age group.

Sudden unexpected death in infancy and childhood requires a 'full' post-mortem investigation. Guidance from the Royal College of Pathologists recommends sampling of all the major organs. However, the diaphragm does not feature in this or in most lists of routine histology. Our aim is to emphasize the importance of sampling the diaphragm for histological examination during autopsy. We describe three autopsy cases of clinically unexplained death in the perinatal and paediatric age group that showed significant pathology of the diaphragm. In Case 1, a previously healthy five-year-old girl collapsed suddenly and died four days later. In Case 2, an eight-month-old infant had repeated episodes of respiratory arrest that culminated in death. Autopsy demonstrated a predominantly diaphragmatic myositis. In Case 3 a female neonate had a respiratory arrest three days after birth and died less than a month later. Autopsy showed multiple large calcified necrotic fibres in the diaphragm. The diaphragm is seldom sampled at autopsy. In the first two cases a predominantly diaphragmatic myositis was either the direct or underlying cause of death. In the third case long-standing diaphragmatic pathology of uncertain cause may have contributed to the original respiratory arrest. Had the diaphragm not been examined histologically, the cause of death would have remained unascertained in these cases. In cases of sudden death in infancy and childhood, failure to reach a diagnosis may lead to undue suspicion falling upon the child's carers. This underscores the need for full histology at post-mortem in child deaths, including diaphragmatic sampling.

A randomized, prospective, multisite comparison of pediatric prehospital training methods.

OBJECTIVE: Results of prehospital pediatric continuing education using train-the-trainer and CD-ROM training methods were compared to each other and to a control group. The null hypothesis was that no differences would be found in pretraining and posttraining measurements of knowledge and performance by either training method. METHODS: This was a prospective trial involving 12 sites. Random selections were made from ambulance service lists provided by 3-state emergency medical services (EMS) agencies. Preintervention and postintervention (12-month) measurements included a written examination and 2 performance scenarios videotaped for independent panel evaluation. Training was either an interactive CD-ROM or standard classroom instruction using a train-the-trainer model. Mean differences in written, performance, and combined scores were analyzed. RESULTS: Differences were noted in the combined and performance scores for the CD-ROM intervention group. No differences were noted in written measurements between or among the groups. CONCLUSION: In this small sample, interactive CD-ROM training shows promise for improving performance. The research design, with additional guards against sample size attrition, may provide a model for multisite EMS education research.

Recruitment by motor nerve root stimulators: significance for implant design.

Three paraplegics have been implanted with stimulators of the lumbar anterior roots. Twelve roots were trapped in slots, each with three electrodes, a central cathode and two anodes, but the anodes in all the slots were connected together to reduce the number of wires. Cross-talk between roots was observed at lower levels than expected. Cross-talk was assessed from the ratio of the root's threshold to the threshold of the contralateral response (expected ratio: 72). Two hypothetical reasons for this low ratio were: that the cathode current was not equally shared by the anodes; or that the contralateral responses were reflex. Experiments showed that neither explanation was valid. The ratio of the contralateral to ipsilateral threshold for individual slots (K(1)) was sometimes low because the ipsilateral threshold was high. By taking the ratio of the lowest contralateral response to lowest ipsilateral response, for all roots in each subject (K(2)), the ratio should approach the theoretical value. However, for the two subjects with small slots, it was 7.9 and 15.3, much less than 72, suggesting that the original theory was incorrect. Approximate calculations of the activation function suggest that the reason may be that roots which run close to a slot, but not through it, may pass through a virtual anode region outside the ends of the slots, and that anodal break stimulation in those regions causes the cross-talk. Our estimate is that this cross-talk would be expected to occur at intensities above 5.3 times the cathodal threshold. If the roots are stimulated in pairs, below the levels of cross-talk, experimental results show that the moments obtained in response are additive to within 5%.

Functional electrical stimulation and rehabilitation--an hypothesis.

Functional Electrical Stimulation (FES), used to mimic a weak or paralysed movement, sometimes is followed by a specific recovery of voluntary power in that movement. The mechanism by which this occurs is unclear, and the presumption has often been that FES may somehow promote adaptive changes in cortical connectivity. However, the unique feature of electrical stimulation is that it activates nerve fibres both orthodromically and antidromically. The antidromic impulse in motor nerve fibres will reach the anterior horn cell, but it can go no further up the neuraxis. If the corticospinal-anterior horn cell synapse is a Hebb-type modifiable synapse (i.e. one that is strengthened by the coincidence of presynaptic and postsynaptic activity), then FES, combined with coincident voluntary effort through a damaged pyramidal motor system, could help to promote restorative synaptic modifications at anterior horn cell level, by this unique adaptive mechanism.