The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.

Rapid changes in the level of Kluane Lake in Yukon Territory over the last millennium

The level of Kluane Lake, the largest lake in Yukon Territory, was lower than at present during most of the Holocene. The lake rose rapidly in the late seventeenth century to a level 12 m above present, drowning forest and stranding driftwood on a conspicuous high-stand beach, remnants of which are preserved at the south end of the lake. Kluane Lake fell back to near its present level by the end of the eighteenth century and has fluctuated within a range of about 3 m over the last 50 yr. The primary control on historic fluctuations in lake level is the discharge of Slims River, the largest source of water to the lake. We use tree ring and radiocarbon ages, stratigraphy and sub-bottom acoustic data to evaluate two explanations for the dramatic changes in the level of Kluane Lake. Our data support the hypothesis of Hugh Bostock, who suggested in 1969 that the maximum Little Ice Age advance of Kaskawulsh Glacier deposited large amounts of sediment in the Slims River valley and established the present course of Slims River into Kluane Lake. Bostock argued that these events caused the lake to rise and eventually overflow to the north. The overflowing waters incised the Duke River fan at the north end of Kluane Lake and lowered the lake to its present level. This study highlights the potentially dramatic impacts of climate change on regional hydrology during the Little Ice Age in glacierised mountains. © 2006 University of Washington.

Nationalism, Territory, and Organized Violence: Introduction to the Special Issue

Recent decades have seen significant advances in research on the relationship between nationalist ideology and organized violence. New scholarship has paid much closer attention to the microdynamics of violence, the strikingly uneven distribution of violence, the relationship between master cleavages and intimate local and personal struggles, and to process, history, and contingency. Nationalist ideology is understood to be bound up intimately with institutions and with everyday relationships at the local level. We introduce the contributions to this special issue, outlining the way in which they highlight the power of ideas, narratives, and microlevel solidarity in mobilization for violence and how they address the crucial importance of territoriality in linking ideas and action.

The place of sperm DNA fragmentation testing in current day fertility management

In this debate article, I am going to set out the case that sperm DNA fragmentation testing is essential in current day fertility management because-
• Our current semen analysis testing is unfit for purpose
• Sperm DNA damage testing has strong associations with every fertility check point
• Sperm DNA damage testing has strong associations with miscarriage
• Sperm DNA testing can explain ‘unexplained’ infertility
• There are reasons why sperm with poor DNA are successful in ICSI
• There are no non-invasive sperm function tests that provide the same information
• We need to take a fresh look at the ‘evidence’ against sperm DNA testing
• We have no reason to wait. There are benefits for clinics and couples alike.

Fragmentation of Neutral Amino Acids and Small Peptides by Intense, Femtosecond Laser Pulses

High power femtosecond laser pulses have unique properties that could lead to their application as ionization or activation sources in mass spectrometry. By concentrating many photons into pulse lengths approaching the timescales associated with atomic motion, very strong electric field strengths are generated, which can efficiently ionize and fragment molecules without the need for resonant absorption. However, the complex interaction between these pulses and biomolecular species is not well understood. To address this issue, we have studied the interaction of intense, femtosecond pulses with a number of amino acids and small peptides. Unlike previous studies, we have used neutral forms of these molecular targets, which allowed us to investigate dissociation of radical cations without the spectra being complicated by the action of mobile protons. We found fragmentation was dominated by fast, radical-initiated dissociation close to the charge site generated by the initial ionization or from subsequent ultrafast migration of this charge. Fragments with lower yields, which are useful for structural determinations, were also observed and attributed to radical migration caused by hydrogen atom transfer within the molecule.

Beyond Divided Territory::How Changing Understandings of Public Space in Northern Ireland can Facilitate New Identity Dynamics

The sectarian geography of Northern Ireland, whereby the majority of the population live in areas predominated by one religion or the other, is typically assumed to straightforwardly reflect the territorial identities of local residents. This conflation of place and identity neglects the role of place in actively shaping and changing the behaviours occurring within them. The present paper uses new developments in the area of social psychology to examine three case studies of place identity in Northern Ireland and explore the possibilities for change. A large scale survey of the display of flags and emblems across Northern Ireland demonstrates the extent of visible ter-ritorialisation, but also the relationship between understandings of space and the acceptability of these displays. Secondly, analysis of interviews with the Orange Or-der and nationalist residents concerning the Drumcree dispute illustrates how differ-ent constructions of space are used to claim and counterclaim rights to display iden-tity. Finally analysis of media and interview accounts of the St Patrick’s Day event in Belfast illustrate how new understandings of shared space can negate territorial identities and facilitate coexistence in the same place and facilitate good relations.

The Map Defines the Territory: Remodelling NGO Partnerships for Knowledge Translation in Transition Contexts

The initial impetus for a theoretical exploration of organisational relationships is based on case study research on a Bulgarian NGO's implementation of values and goals into practices under a guiding relationship from a very experienced UK organisation in the same field. Findings diverged from conventional accounts of developing NGOs' dependence on more developed counterparts and that case study findings characterised the inter- dependency between the two organisations as more alike to a collaborative knowledge ...

The Effect of the Secret Ballot on Party System Fragmentation: A Test of Three Competing Arguments

Few studies have examined the impact that the adoption of the secret ballot had on party system fragmentation outside the United States. This article tests arguments maintaining that the adoption of the secret ballot had a negative, positive or nil effect on party system fragmentation. Using time-series cross-sectional data from
several countries adopting the secret ballot around the turn of the twentieth century, the results demonstrate that the adoption of the secret ballot did not hinder – though did not favour, either – the development of multiparty systems.

The organizational ecology of ethnic cleavages: The nonlinear effects of ethnic diversity on party system fragmentation

The conventional wisdom regarding party system fragmentation assumes that the effects of electoral systems and social cleavages are linear. However, recent work applying organizational ecology theories to the study of party systems has challenged the degree to which electoral system effects are linear. This paper applies such concepts to the study of social cleavages. Drawing from theories of organizational ecology and the experience of many ethnically diverse African party systems, I argue that the effects of ethnic diversity are nonlinear, with party system fragmentation increasing until reaching moderate levels of diversity before declining as diversity reaches extreme values. Examining this argument cross-nationally, the results show that accounting for nonlinearity in ethnic diversity effects significantly improves model fit.

Fragmentation of CD+ induced by intense ultrashort laser pulses

The fragmentation of CD+ in intense ultrashort laser pulses was investigated using a coincidence three-dimensional momentum imaging technique improved by employing both transverse and longitudinal electric fields. This allowed clear separation of all fragmentation channels and the determination of the kinetic energy release down to nearly zero, for a molecule with significant mass asymmetry. The most probable dissociation pathways for the two lowest dissociation limits, C+ + D and C+ D+, were identified for both 22-fs, 798-nm and 50-fs, 392-nm pulses. Curiously, the charge asymmetric dissociation of CD2+ was not observed for 392-nm photons, even though it was clearly visible for the fundamental 798 nm at the same peak intensity.

Not all social cleavages are the same: On the relationship between religious diversity and party system fragmentation

Most studies examining the relationship between social cleavages and party system fragmentation maintain that higher levels of social diversity lead to greater party system fragmentation. However, most aggregate-level studies focus on one type of social cleavage:ethnic diversity. In order to develop a better understanding of how different cleavages impact electoral competition, this paper considers another type of social cleavage: religious diversity.Contrary to previous literature, higher levels of religious diversity provide incentives for cross-religious cooperation, which in turn reduces party system fragmentation. Using a cross national data set of elections from 1946-2011, the results show that, in contrast to most studies examining the effects of social cleavage diversity on the number of parties, higher religious diversity is associated with lower levels of party system fragmentation.

Electron impact fragmentation of thymine:partial ionization cross sections for positive fragments

We have measured mass spectra for positive ions for low-energy electron impact on thymine using a reflectron time-of-flight mass spectrometer. Using computer controlled data acquisition, mass spectra have been acquired for electron impact energies up to 100 eV in steps of 0.5 eV. Ion yield curves for most of the fragment ions have been determined by fitting groups of adjacent peaks in the mass spectra with sequences of normalized Gaussians. The ion yield curves have been normalized by comparing the sum of the ion yields to the average of calculated total ionization cross sections. Appearance energies have been determined. The nearly equal appearance energies of 83 u and 55 u observed in the present work strongly indicate that near threshold the 55 u ion is formed directly by the breakage of two bonds in the ring, rather than from a successive loss of HNCO and CO from the parent ion. Likewise 54 u is not formed by CO loss from 82 u. The appearance energies are in a number of cases consistent with the loss of one or more hydrogen atoms from a heavier fragment, but 70 u is not formed by hydrogen loss from 71 u.