'TB or not TB': the conundrum of pre-European contact tuberculosis in the Pacific.

Tuberculosis (TB) is a major global health threat, infecting one-third of the world's population. Despite this prominence, the age, origin and spread of the disease have been topics of contentious debate. Molecular studies suggest that Mycobacterium tuberculosis 'sensu stricto', the most common strain of TB infecting humans today, originated in Africa and from there spread into Europe and Asia. The M. tuberculosis strains most commonly found across the Pacific and the Americas today are most closely related to European strains, supporting a hypothesis that the disease only reached these regions relatively recently via European sailors or settlers. However, this hypothesis is inconsistent with palaeopathological evidence of TB-like lesions in human remains from across the Pacific that predate European contact. Similarly, genetic evidence from pre-European South American mummies challenges the notion of a European introduction of the disease into the Pacific. Here, we review the complex evidence for the age and origin of TB in the Pacific, and discuss key gaps in our knowledge and how these may be addressed. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Complex history of dog (Canis familiaris) origins and translocations in the Pacific revealed by ancient mitogenomes.

Archaeological evidence suggests that dogs were introduced to the islands of Oceania via Island Southeast Asia around 3,300 years ago, and reached the eastern islands of Polynesia by the fourteenth century AD. This dispersal is intimately tied to human expansion, but the involvement of dogs in Pacific migrations is not well understood. Our analyses of seven new complete ancient mitogenomes and five partial mtDNA sequences from archaeological dog specimens from Mainland and Island Southeast Asia and the Pacific suggests at least three dog dispersal events into the region, in addition to the introduction of dingoes to Australia. We see an early introduction of dogs to Island Southeast Asia, which does not appear to extend into the islands of Oceania. A shared haplogroup identified between Iron Age Taiwanese dogs, terminal-Lapita and post-Lapita dogs suggests that at least one dog lineage was introduced to Near Oceania by or as the result of interactions with Austronesian language speakers associated with the Lapita Cultural Complex. We did not find any evidence that these dogs were successfully transported beyond New Guinea. Finally, we identify a widespread dog clade found across the Pacific, including the islands of Polynesia, which likely suggests a post-Lapita dog introduction from southern Island Southeast Asia.

Ancient mitogenomes of Phoenicians from Sardinia and Lebanon: A story of settlement, integration, and female mobility.

The Phoenicians emerged in the Northern Levant around 1800 BCE and by the 9th century BCE had spread their culture across the Mediterranean Basin, establishing trading posts, and settlements in various European Mediterranean and North African locations. Despite their widespread influence, what is known of the Phoenicians comes from what was written about them by the Greeks and Egyptians. In this study, we investigate the extent of Phoenician integration with the Sardinian communities they settled. We present 14 new ancient mitogenome sequences from pre-Phoenician (~1800 BCE) and Phoenician (~700-400 BCE) samples from Lebanon (n = 4) and Sardinia (n = 10) and compare these with 87 new complete mitogenomes from modern Lebanese and 21 recently published pre-Phoenician ancient mitogenomes from Sardinia to investigate the population dynamics of the Phoenician (Punic) site of Monte Sirai, in southern Sardinia. Our results indicate evidence of continuity of some lineages from pre-Phoenician populations suggesting integration of indigenous Sardinians in the Monte Sirai Phoenician community. We also find evidence of the arrival of new, unique mitochondrial lineages, indicating the movement of women from sites in the Near East or North Africa to Sardinia, but also possibly from non-Mediterranean populations and the likely movement of women from Europe to Phoenician sites in Lebanon. Combined, this evidence suggests female mobility and genetic diversity in Phoenician communities, reflecting the inclusive and multicultural nature of Phoenician society.

A cryogenic optical feedthrough using polarization maintaining fibers.

Polarization maintaining optical fibers can be used to transmit linearly polarized light over long distances but their use in cryogenic environments has been limited by their sensitivity to temperature changes and associated mechanical stress. We investigate experimentally how thermal stresses affect the polarization maintaining fibers and model the observations with Jones matrices. We describe the design, construction, and testing of a feedthrough and fiber termination assembly that uses polarization maintaining fiber to transmit light from a 633 nm HeNe laser at room temperature to a homodyne polarization-based interferometer in a cryogenic vacuum. We report on the efficiency of the polarization maintaining properties of the feedthrough assembly. We also report that, at cryogenic temperatures, the interferometer can achieve a sensitivity of 8 × 10(-10) rad/√Hz at 0.05 Hz using this feedthrough.

The influence of cues and stimulus history on the non-linear frequency characteristics of the pursuit response to randomized target motion.

When humans pursue motion stimuli composed of alternating constant velocity segments of randomised duration (RD), they nevertheless initiate anticipatory eye deceleration before stimulus direction changes at a pre-programmed time based on averaging prior stimulus timing. We investigated, in both the time and frequency domains, how averaging interacts with deceleration cues by comparing responses to stimuli composed of segments that were either constant-velocity ramps or half-cycle sinusoids. RDs were randomized within 6 ranges, each comprising 8 RDs and having differing mean RD. In sine responses, deceleration cues could be used to modulate eye velocity for long-range stimuli (RD = 840-1,200 ms) but in the shortest range (RD = 240-660 ms) cues became ineffective, so that sine responses resembled ramp responses, and anticipatory timing was primarily dependent on averaging. Additionally, inclusion of short duration (240 ms) segments reduced peak eye velocity for all RDs within a range, even when longer RDs in the range (up to 1,080 ms) would normally elicit much higher velocities. These effects could be attributed to antagonistic interactions between visually driven pursuit components and pre-programmed anticipatory deceleration components. In the frequency domain, the changes in peak velocity and anticipatory timing with RD range were translated into non-linear gain and phase characteristics similar to those evoked by sum-of-sines stimuli. Notably, a reduction in pursuit gain occurred when high-frequency components associated with short duration segments were present. Results appear consistent with an adapted pursuit model, in which pre-programmed timing information derived from an internally reconstructed stimulus signal is stored in short-term memory and controls the initiation of predictive responses.

The role of topical antibiotics used as prophylaxis in surgical site infection prevention.

Compared with systemic antibiotic therapy, the topical or local delivery of an antibiotic has many potential advantages. However, local antibiotics at the surgical site have received very limited approval in any of the surgical prophylaxis consensus guidelines that we are aware of. A review of the literature was carried out through searches of peer-reviewed publications in PubMed in the English language over a 30 year period between January 1980 and May 2010. Both retrospective and prospective studies were included, as well as meta-analyses. With regard to defining 'topical' or 'local' antibiotic application, the application of an antibiotic solution to the surgical site intraoperatively or immediately post-operatively was included. A number of surgical procedures have been shown to significantly benefit from perioperative topical prophylaxis, e.g. joint arthroplasty, cataract surgery and, possibly, breast augmentation. In obese patients undergoing abdominal surgery, topical surgical prophylaxis is also proven to be beneficial. The selective use of topical antibiotics as surgical prophylaxis is justified for specific procedures, such as joint arthroplasty, cataract surgery and, possibly, breast augmentation. In selective cases, such as obese patients undergoing abdominal surgery, topical surgical prophylaxis is also proven to be beneficial. Apart from these specific indications, the evidence for use of topical antibiotics in surgery is lacking in conclusive randomized controlled trials.

Reporting of meticillin-resistant and -susceptible Staphylococcus aureus on death certificates in Irish hospitals.

The documentation of infection with meticillin-resistant Staphylococcus aureus (MRSA) on death certificates has been the subject of considerable public discussion. Using data from five tertiary referral hospitals in Ireland, we compared the documentation of MRSA and meticillin-susceptible S. aureus (MSSA) on death certificates in those patients who died in hospital within 30 days of having MRSA or MSSA isolated from blood cultures. A total of 133 patients had MRSA or MSSA isolated from blood cultures within 30 days of death during the study period. One patient was excluded as the death certificate information was not available; the other 132 patients were eligible for inclusion. MRSA and MSSA were isolated from blood cultures in 59 (44.4%) and 74 (55.6%) cases respectively. One patient was included as a case in both categories as both MRSA and MSSA were isolated from a blood culture. In 15 (25.4%) of the 59 MRSA cases, MRSA was documented on the death certificate. In nine (12.2%) of the 74 patients with MSSA cases, MSSA was documented on the death certificate. MRSA was more likely to be documented on the death certificate than MSSA (odds ratio: 2.46; 95% confidence interval: 1.01-6.01; P < 0.05). These findings indicate that there may be inconsistencies in the way organisms and infections are documented on death certificates in Ireland and that death certification data may underestimate the mortality related to certain organisms. In particular, there appears to be an overemphasis by certifiers on the documentation of MRSA compared with MSSA.

Predicting the unpredictable: weighted averaging of past stimulus timing facilitates ocular pursuit of randomly timed stimuli.

In motor control, prediction of future events is vital for overcoming sensory-motor processing delays and facilitating rapid and accurate responses in a dynamic environment. In human ocular pursuit this is so pervasive that prediction of future target motion cannot easily be eliminated by randomizing stimulus parameters. We investigated the prediction of temporally randomized events during pursuit of alternating constant-velocity (ramp) stimuli in which the timing of direction changes varied unpredictably over a given range. Responses were not reactive; instead, smooth eye velocity began to decelerate in anticipation of each target reversal. In the first experiment, using a continuous-motion stimulus, we found that the time at which this occurred was relatively constant regardless of ramp duration, but increased as mean ramp duration of the range increased. Regression analysis revealed a quantitative association between deceleration timing and the previous two or three ramp durations in a trial, suggesting that recent stimulus history was used to create a running average of anticipatory timing. In the second experiment, we used discrete motion stimuli, with intervening periods of fixation, which allowed both target velocity and reversal timing to be varied, thereby decoupling ramp duration and displacement. This enabled us to confirm that the timing of anticipatory deceleration was based on the history of timing, rather than displacement, within the stimulus. We conclude that this strategy is used to minimize error amid temporal uncertainty, while simultaneously overcoming inherent delays in visuomotor processing.

Cost-effectiveness of employing a total parenteral nutrition surveillance nurse for the prevention of catheter-related bloodstream infections.

The cost of catheter-related bloodstream infection (CRBSI) is substantial in terms of morbidity, mortality and financial resources. Total parenteral nutrition (TPN) is a recognised risk factor for CRBSI. In 1997, an intravenous nutrition nurse was promoted to TPN surveillance clinical nurse manager (CNM) and quarterly infection audit meetings were introduced to monitor trends in CRBSI. Data were prospectively collected over a 15-year period using specific TPN records in a 535-bed tertiary acute university hospital. A total of 20 439 CVC-days and 307 CRBSIs were recorded. Mean number of infections before, and after, the introduction of a dedicated TPN surveillance CNM were compared. Mean CRBSI per 1000 catheter-days+/-SD was 20.5+/-6.34 prior to 1997 and 14.64+/-7.81 after 1997, representing a mean reduction of 5.84 CRBSIs per 1000 catheter-days (95% CI: -4.92 to 16.60; P=0.05). Mean number of CRBSIs per year+/-SD was 28.3+/-4.93 prior to 1997 and 18.5+/-7.37 after 1997, representing a mean decrease of 9.8 infections per year (95% CI: 0.01 to 19.66; P<0.05). The savings made by preventing 9.8 infections per year were calculated from data on bed-days obtained from the hospital finance office. The cost in hospital days saved per annum was euro135,000. Introduction of a TPN surveillance CNM saved the hospital at least euro78,300 per annum and led to a significant decrease in CRBSIs in TPN patients.

Internally generated smooth eye movement: its dynamic characteristics and role in randomised and predictable pursuit.

Although originally examined in the context of prediction, it is now apparent that smooth eye movements generated by internal (extra-retinal) mechanisms play a role in both predictable and randomised pursuit responses. Internally generated responses are characterised by trajectories that begin with an increasing acceleration that develops much more slowly than responses generated through retinal feedback, but which can, nevertheless, reach high velocities. They can be evoked by regularly repeated motion stimuli or by cues that occur at a regular time before target motion onset. Although frequently observed as anticipatory movements, we now provide evidence that such movements also form the basis of the extra-retinal component of a randomised step-ramp response. In such circumstances they also build up slowly in the first second or so of the initial response. They are normally masked in the presence of visual feedback, but can be revealed by prolonged target extinction immediately after response initiation. The key to release internally generated responses in both random and predictable conditions is expectation of future target motion. The key to their functionality is rapid acquisition and storage of velocity and timing information.

Evidence for a link between the extra-retinal component of random-onset pursuit and the anticipatory pursuit of predictable object motion.

During pursuit of moving targets that temporarily disappear, residual smooth eye movements represent the internal (extra-retinal) component of pursuit. However, this response is dependent on expectation of target reappearance. By comparing responses with and without such expectation during early random-onset pursuit, we examined the temporal development of the extra-retinal component and compared it with anticipatory pursuit, another form of internally driven response. In an initial task (mid-ramp extinction), a moving, random-velocity target was initially visible for 100 or 150 ms but then extinguished for 600 ms before reappearing and continuing to move. Responses comprised an initial visually driven rapid rise in eye velocity, followed by a secondary slower increase during extinction. In a second task (short ramp), with identical initial target presentation but no expectation of target reappearance, the initial rapid rise in eye velocity was followed by decay toward zero. The expectation-dependent difference between responses to these tasks increased in velocity during extinction much more slowly than the initial, visually driven component. In a third task (initial extinction), the moving target was extinguished at motion onset but reappeared 600 ms later. Repetition of identical stimuli evoked anticipatory pursuit triggered by initial target offset. Temporal development and scaling of this anticipatory response, which was based on remembered velocity from prior stimuli, was remarkably similar to and covaried with the difference between mid-ramp extinction and short ramp tasks. Results suggest a common mechanism is responsible for anticipatory pursuit and the extra-retinal component of random-onset pursuit, a finding that is consistent with a previously developed model of pursuit.

The influence of briefly presented randomized target motion on the extraretinal component of ocular pursuit.

We assessed the ability to extract velocity information from brief exposure of a moving target and sought evidence that this information could be used to modulate the extraretinal component of ocular pursuit. A step-ramp target motion was initially visible for a brief randomized period of 50, 100, 150, or 200 ms, but then extinguished for a randomized period of 400 or 600 ms before reappearing and continuing along its trajectory. Target speed (5-20 degrees /s), direction (left/right), and intertrial interval (2.7-3.7 s) were also randomized. Smooth eye movements were initiated after about 130 ms and comprised an initial visually dependent component, which reached a peak velocity that increased with target velocity and initial exposure duration, followed by a sustained secondary component that actually increased throughout extinction for 50- and 100-ms initial exposures. End-extinction eye velocity, reflecting extraretinal drive, increased with initial exposure from 50 to 100 ms but remained similar for longer exposures; it was significantly scaled to target velocity for 150- and 200-ms exposures. The results suggest that extraretinal drive is based on a sample of target velocity, mostly acquired during the first 150 ms, that is stored and forms a goal for generating appropriately scaled eye movements during absence of visual input. End-extinction eye velocity was significantly higher when target reappearance was expected than when it was not, confirming the importance of expectation in generating sustained smooth movement. However, end-extinction eye displacement remained similar irrespective of expectation, suggesting that the ability to use sampled velocity information to predict future target displacement operates independently of the control of smooth eye movement.

The occluded onset pursuit paradigm: prolonging anticipatory smooth pursuit in the absence of visual feedback.

Humans can produce anticipatory smooth pursuit (ASP) for a few hundred ms prior to the appearance of a moving target. Once visual feedback is available, however, it is difficult to distinguish ASP from the visually-driven response with which it merges. Here we have developed a paradigm that extends the anticipatory period to show unequivocally how ASP can evolve over periods of up to 600 ms before being influenced by visual feedback. ASP was evoked by repeated presentation of constant velocity (ramp) stimuli preceded by auditory cues. The target was occluded during the initial part of the ramp, so that when it became visible it had already moved to an eccentric position. The occlusion period (T occ) varied from 0 to 500 ms in 100 ms increments; for each period ramps were presented in blocks of 8 with velocity held constant at 8, 16, 24 or 32 degrees/s. Eye displacement trajectories showed that subjects attempted to match the unseen target trajectory with a mixture of saccades and smooth pursuit. The smooth component was initiated progressively earlier in relation to target appearance as T occ increased, leading to progressively higher ASP gains by the time the target became visible. This prolongation of ASP throughout the occlusion period reveals the underlying internal drive that produces it, a drive that under normal circumstances quickly becomes masked by visual feedback.

Attention and selection for predictive smooth pursuit eye movements.

Humans cannot typically produce smooth eye movements in the absence of a moving stimulus. However, they can produce predictive smooth eye movements if they expect a target of a known velocity to reappear. Here, we observed that participants could extract velocity information from two simultaneously presented moving targets in order to produce a subsequent predictive smooth eye movement for one of the two targets. Subjects fixated a stationary cross during the presentation of two targets, moving rightward at different velocities. In the next presentation, a single target was presented, which participants tracked with their eyes. A static cue, presented 700 ms before the moving target, indicated which of the two targets would be presented. Predictive eye movements were of an appropriate velocity, even when participants did not know in advance which of the two targets would subsequently be cued. However, the scaling of predictive eye velocity was marginally less accurate in this divided attention condition than when participants knew the identity of the cued target in advance, or a single target was presented during fixation. In a second experiment, we found that the velocity cued on the previous trial had a greater effect than the uncued velocity on the current trial. The negligible effect of the uncued velocity indicates that participants were extremely effective at selectively reproducing one of two recently viewed velocities. However, other influences, such as past history, also affected predictive smooth eye movements.

Scaling of smooth anticipatory eye velocity in response to sequences of discrete target movements in humans.

We investigated the ability to generate anticipatory smooth pursuit to sequences of constant velocity (ramp) stimuli of increasing complexity. Previously, it was shown that repeated presentation of sequences composed of four ramps with two speeds in two directions, evoked anticipatory smooth pursuit after only one or two presentations. Here, sequences of four or six ramps, each having a choice of four speeds and either one or two directions (uni- or bi-directional) were examined. The components of each sequence were presented as discrete ramps (duration: 400 ms; randomised velocity: 10-40 degrees/s), each starting from the centre with 1,200 ms periods of central fixation between ramps, allowing anticipatory activity to be segregated from prior eye movement. Auditory warning cues occurred 600 ms prior to each target presentation. Anticipatory smooth eye velocity was assessed by calculating eye velocity 50 ms after target onset (V 50), prior to the availability of visual feedback. Despite being required to re-fixate centre during inter-ramp gaps, subjects could still generate anticipatory smooth pursuit with V 50 comparable to single speed control sequences, but with less accuracy. In the steady state V 50 was appropriately scaled in proportion to upcoming target velocity for each ramp component and thus truly predictive. Only one to two repetitions were required to attain a steady-state for unidirectional sequences (four or six ramps), but three or four repeats were required for bi-directional sequences. Results suggest working memory can be used to acquire multiple levels of velocity information for prediction, but its use in rapid prediction is compromised when direction as well as speed must be retained.

Predicting the duration of ocular pursuit in humans.

This study examines the effects of expectation on the timing of ocular pursuit termination. Human subjects pursued repeated, constant velocity (15 or 30 degrees/s) target motion stimuli (ramps), moving left or right. Ramps were of constant duration (RD = 240, 480, 720 or 960 ms), resulting in anticipatory slowing of eye velocity prior to ramp termination and target extinction. At unexpected intervals RD was increased or decreased, but velocity remained constant. When RD increased eye velocity continued to decline, even though the target remained visible and continued to move. It took approximately 180 ms before eye velocity started to recover towards the steady state velocity level for the continued target motion. When RD decreased, eye velocity continued as if for a longer ramp duration, again taking approximately 180 ms before eye velocity started to decrease. These results suggest that timing of the response to the expected ramp duration had been pre-programmed on the basis of prior experience of ramp duration. Moreover, adjustments to timing occurred rapidly, within the second presentation of the new RD. Responses were compared to control conditions with randomised ramp duration. Eye velocity declined later in the controls for RD < or = 720 ms, as expected, but exhibited similar decline in predictable and randomised conditions for RD = 960 ms. Further controls established that eye velocity could only be reliably maintained until the end of the ramp when the target was expected to continue in motion after the end of the ramp. The results suggest that estimates of stimulus duration are made continuously in all conditions, based on expectancy of target termination.

Target selection for predictive smooth pursuit eye movements.

Previous work has indicated that after exposure to a moving stimulus, people are able to produce predictive smooth eye movements prior to reappearance of the stimulus. Here, we investigated whether subjects are able to extract relevant velocity information from two simultaneously presented targets and use this information to produce a subsequent predictive response. A trial consisted of a series of two or five presentations of moving stimuli, preceded 500 ms earlier by an audio warning cue. In the first one or four presentations, subjects fixated during the presentation of two moving targets and in the final presentation they tracked a single moving target. During fixation, two moving targets were presented concurrently, originating from the fixation point and moving horizontally to the right at differing velocities (10, 20, 30 or 40 degrees /s), with each target being presented at the same velocity throughout a trial. In the tracking presentation, the fixation cross was extinguished and only a single target was presented, which the subjects were required to track with their eyes. To cue which of the two targets would be presented, the appropriate target was presented statically at the same time as the audio warning cue. A significant relationship was found between eye velocity 100 ms after the start of the tracking target (i.e. prior to visual feedback) and the cued target velocity. Thus, subjects were able to make predictive eye movements that were of appropriate velocity for the cued target, despite fixating and being uncertain which target was relevant, during previous exposure.